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A Twin Study of Depression Symptoms, Hypertension, and Heart Disease in Middle-Aged Men
Abstract
Epidemiological and clinical studies have established an association between major depression and cardiovascular disease. We utilized a twin design to test whether there are common genetic and environmental risk factors underlying depression symptoms, hypertension and heart disease.
Association studies were conducted with 6,903 male-male twins from the Vietnam Era Twin Registry who responded to both a 1990 health questionnaire and a 1992 telephone administration of a structured psychiatric interview. Data from 2,731 complete twin pairs were used to fit genetic models which determined the extent to which lifetime depression symptoms, heart disease and hypertension shared genetic and/or environmental factors.
Heart disease was significantly associated with 1-4 symptoms and 5 or more symptoms of depression (odds ratio [OR] = 2.62; 95% confidence interval [CI]: 1.54-4.46 and OR = 4.02; 95% CI: 2.16-7.46). Hypertension was significantly associated with 1 to 4 symptoms and 5 or more symptoms of depression (OR = 1.29; 95% CI: 1.11-1.50 and OR = 1.49; 95% CI: 1.21-1.83). The genetic correlations were significant between depression symptoms and hypertension (r =.19), and between depression symptoms and heart disease (r =.42). Of the total variance in depression, 8% was common to hypertension and heart disease, 7% of the variance in hypertension was common with depression symptoms and heart disease, and 64% of the variance in heart disease was common with depression symptoms and hypertension.
Men who reported cardiovascular disease were significantly more likely to have depression symptoms. The lifetime co-occurrence of these phenotypes is partly explained by common genetic risk factors.
... [29] Genetic Factors: The apparent familial predisposition seen in both depression and CVD has been demonstrated in twin studies. [30,31] Their work with mono-and dizygotic twins revealed that heart disease and hypertension were significantly associated with five depressive symptoms and that this association could be explained by genetics, and that depression and CVD shared a common genetic basis. ...
... Studies have shown that the physiological and behavioral effects of repeated stress and hostile interactions prevent the beneficial effects of drugs on plaques in the vessels. [29,30] Smoking: It has been shown that mortality due to MI decreases in individuals with CVD who stop smoking. A close relationship between depression and increased smoking is known. ...
... The way of thinking, "If I'm going to die, why should I put myself in more trouble?" is common in patients with depression. [30,33] ...
The relationship between cardiovascular diseases (CVD) and psychiatric diseases is bidirectional and these two common conditions can occur together. Depression is thought to act as a risk factor in the occurrence and progression of CVD in this association. In this review, the studies examining the interaction between CVD and depression and the pathogenesis of this interaction will be reviewed. The emphasis will be on whether depression is a modifiable factor in CVD and whether its treatment can improve survival. We also aim to draw attention to how depression, which is already on the rise in the general population after the coronavirus disease 2019 (COVID-19) pandemic, has changed with CVD and COVID-19.
... To date, the bidirectional association between depression and cardiovascular disease have been examined in three twin studies with different design and findings. In a cross-sectional study from the Vietnam Era Twin Registry including 2731 male twin pairs, a strong correlation between depression and cardiovascular disease, assessed by a self-report questionnaire, was mainly explained by genetic factors [15]. A cohort study from the Swedish twin registry included 15,284 twin pairs with depression, assessed by personal interview and followed these twins for register-based coronary artery disease diagnosis. ...
... Our results do not confirm the results of the twin studies that found strong (+0.42) [15] or modest (+0.12-+0.14) [16] genetic correlations between cardiovascular disease and depressive symptoms. ...
... The twin cohorts also differed by age. In the cross-sectional Vietnamese Twin Study, the twins had a mean age of 42 years [15], whereas the mean age was 57 in the Swedish twin cohort and age at disease onset was not accounted for, although the heritability of depression [28] and cardiovascular disease [29] seems to vary with age at onset. Another study from the Swedish twin register including 4785 twins found that the risk of cardiovascular disease was higher in twins with a cotwin who had a late-onset depression than in those whose co-twin had an early-onset depression [30]. ...
Depression and cardiovascular disease (ischemic heart disease and stroke) are associated in a bidirectional manner. Their relatively high heritability has led to the hypothesis that this co-occurrence is related to shared familial and genetic factors; this study aims to test this hypothesis. We included 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry followed from January 1977 until December 2011 in nationwide Danish registries. We used survival analyses accounting for censoring and competing risk of death to estimate cumulative incidence, casewise concordance, relative recurrence risk, and heritability of the co-occurrence of depression and cardiovascular disease by age using monozygotic and same-sex dizygotic twin pairs. The casewise concordance of ischemic heart disease or stroke in twins whose co-twin was diagnosed with depression was at all ages similar for the monozygotic and dizygotic twin pairs and to the cumulative incidence of ischemic heart disease or stroke, respectively, in the entire twin population. A similar pattern was seen in analyses of depression risk given the co-twin being diagnosed with ischemic heart disease or stroke. Relative recurrence risk and heritability estimates were also of modest size and with confidence intervals including unity. Results were similar after stratification by gender as well as when redefining depression to include the use of antidepressant medication from 1995. Our findings do not support that co-occurrence between depression and cardiovascular disease is explainable by shared genetic factors, nor did we find strong evidence of a familial effect.
... Это психическое расстройство, характеризующееся снижением настроения, утратой способности переживать радость, нарушениями мышления, двигательной заторможенностью [1][2][3][4]. Депрессия и связанные с ней душевные страдания и волнения могут привести к развитию артериальной гипертензии (АГ) как у мужчин, так и у женщин [5][6][7][8]. В среднем депрессия повышала риск АГ в 1,42 раза [9]. Есть и совершенно противоположное мнение -высокий уровень тревоги и депрессии является предиктором снижения АД через 11 лет от момента обследования [10][11][12]. ...
... Материал и методы. Случайная репрезентативная выборка лиц 25-64 лет Октябрьского района города Новосибирска (657 мужчин, 689 женщин) обследована в 1994 г. в рамках психосоциального подраздела III скрининга программы ВОЗ «MONICA-psychosocial (MOPSY)» (Мониторирование тенденций заболеваемости и смертности от сердечно-сосудистых заболеваний и определяющих их факторов) [6][7][8][9]. Формирование выборки происходило в соответствии со всеми требованиями вышеупомянутой программы. Для проведения оценки ЖИ предлагалась шкала ЖИ (тест MOPSY). ...
Введение. Депрессия представляет собой относительно распространенное заболевание, охватывающее все слои населения вне зависимости от социального положения. Это психическое расстройство, характеризующееся снижением настроения, утратой способности переживать радость, нарушениями мышления, двигательной заторможенностью [1–4]. Депрессия и связанные с ней душевные страдания и волнения могут привести к развитию артериальной гипертензии (АГ) как у мужчин, так и у женщин [5–8]. В среднем депрессия повышала риск АГ в 1,42 раза [9]. Есть и совершенно противоположное мнение – высокий уровень тревоги и депрессии является предиктором снижения АД через 11 лет от момента обследования [10–12]. В современной литературе практически не раскрыт вопрос об особенностях влияния депрессии на риск развития АГ у мужчин и женщин. Поэтому целью нашего исследования было определить влияние депрессии на риск развития АГ за 16 лет среди лиц 25–64 лет.
... Environmental variances were dependent on shared and additive genetic variances so that e 1 was specified as √ 1 − a 2 1 − c 2 1 and e 2 as √ 1 − a 2 2 − c 2 2 . Additive and shared variances were considered as follows: (A) alcohol use (a 2 49%, c 2 10%) (Verhulst et al. 2015) and heart disease (a 2 22%, c 2 0%) (Wu et al. 2014); (B) BMI (a 2 72%, c 2 3%) (Rokholm et al. 2011) and major depression (a 2 37%, c 2 1%) (Scherrer et al. 2003); (C) cannabis use (a 2 51%, c 2 20%) (Verweij et al. 2010) and schizophrenia (a 2 81%, c 2 11%) (Sullivan et al. 2003); (D) dyslipidemia (LDL) (a 2 60%, c 2 28%) (Zhang et al. 2010) and again heart disease (a 2 22%, c 2 0%) (Wu et al. 2014) (Fig. 3). Figure 3 shows that the power to reject g1 = 0 is quite reasonable Fig. 3 Power curve across R² values for PS1. Parameters set for all groups b 3 = g 1 = g 2 = √ 0.05 , ra = 0.3; rc = 0.25; re = 0.3; rf = 0.25; Environmental variances were dependent on shared and additive genetic variances: e 1 was specified as √ 1 − a 2 1 − c 2 1 and e 2 as √ 1 − a 2 2 − c 2 2 . ...
... Parameters set for all groups b 3 = g 1 = g 2 = √ 0.05 , ra = 0.3; rc = 0.25; re = 0.3; rf = 0.25; Environmental variances were dependent on shared and additive genetic variances: e 1 was specified as √ 1 − a 2 1 − c 2 1 and e 2 as √ 1 − a 2 2 − c 2 2 . Additive and shared variances for the groups: (A) cannabis use (a 2 51%, c 2 20%) (Verweij et al. 2010) and schizophrenia (a 2 81%, c 2 11%) (Sullivan et al. 2003); (B) BMI (a 2 72%, c 2 3%) (Rokholm et al. 2011) and major depression (a 2 37%, c 2 1%) (Scherrer et al. 2003); (C) alcohol use (a 2 49%, c 2 10%) (Verhulst et al. 2015) and heart disease (a 2 22%, c 2 0%) (Wu et al. 2014); (D) dyslipidemia (LDL) (a 2 60%, c 2 28%) (Zhang et al. 2010) and heart disease (a 2 22%, c 2 0%) (Wu et al. 2014). Vertical lines were added to represent R 2 for four PSs reported in recent papers: a, smoking (Pasman et al. 2022); b, BMI (Furlong and Klimentidis 2020); c, LDL (Kuchenbaecker et al. 2019); d, attention deficit hyperactivity disorder (ADHD) (Demontis et al. 2019) and well within values that appeared in recent publications. ...
Establishing causality is an essential step towards developing interventions for psychiatric disorders, substance use and many other conditions. While randomized controlled trials (RCTs) are considered the gold standard for causal inference, they are unethical in many scenarios. Mendelian randomization (MR) can be used in such cases, but importantly both RCTs and MR assume unidirectional causality. In this paper, we developed a new model, MRDoC2, that can be used to identify bidirectional causation in the presence of confounding due to both familial and non-familial sources. Our model extends the MRDoC model (Minică et al. in Behav Genet 48:337–349, https://doi.org/10.1007/s10519-018-9904-4, 2018), by simultaneously including risk scores for each trait. Furthermore, the power to detect causal effects in MRDoC2 does not require the phenotypes to have different additive genetic or shared environmental sources of variance, as is the case in the direction of causation twin model (Heath et al. in Behav Genet 23:29–50, https://doi.org/10.1007/BF01067552, 1993).
... ; https://doi.org/10.1101/150615 doi: bioRxiv preprint instance, the genetic correlation of depression with hypertension is estimated to be 19%, and between depression and heart disease is about 42% (18). The genetic correlation of depressive symptoms with plasma lipids level ranges from 10% to 31% (19), and 12% of the genetic component for depression is shared with obesity (20). ...
... The GSK3B is a target gene for several mood stabilizers including lithium(110,111). the SLC18A1 (rs988713, rs2279709, Thr136Ser) gene confer susceptibility to BPD(115).PPP1R1BA target for dopamine HDL cholesterol rs11869286-G/C (28)DARPP-32 decreased in the prefrontal cortex of BPD patients(116), increased expression was also shown in BPD (117). at the APOE gene contributed to depressive symptoms (120).18 CMD-R: Cardio-metabolic diseases and associated risk factors; SNP: Single nucleotide polymorphism; HDL: High-density lipoprotein; LDL:Low-density lipoprotein; BPD: bipolar disorder; MDD: Major depressive disorder IPA-generated network of genes, as indicated by the dashed lines, shared between coronary artery diseases, hypertension, diabetes mellitus, obesity, MDD and BPD, highlighting ...
Meta-analyses of genome-wide association studies (meta-GWAS) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases, and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardio-metabolic diseases risk (CMD-R) genes that are also associated with mood disorders. Firstly, we reviewed meta-GWA studies published until January 2016, for the diseases “type 2 diabetes, coronary artery disease, hypertension” and/or for the risk factors “blood pressure, obesity, plasma lipid levels, insulin and glucose related traits”. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and “depressive disorder” OR “depressive symptoms” OR “bipolar disorder” OR “lithium treatment”, OR “serotonin reuptake inhibitors treatment”. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes include MTHFR , CACNA1D , CACNB2 , GNAS , ADRB1 , NCAN , REST , FTO , POMC , BDNF , CREB , ITIH4 , LEP , GSK3B , SLC18A1 , TLR4 , PPP1R1B , APOE , CRY2 , HTR1A , ADRA2A , TCF7L2 , MTNR1B , and IGF1 . A pathway analysis of these genes revealed significant pathways: corticotrophin-releasing hormone signaling, AMPK signaling, cAMP-mediated or G-protein coupled receptor signaling, axonal guidance signaling, serotonin and dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our findings provide insights in to the shared biological mechanisms of mood disorders and cardio-metabolic diseases.
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (PT) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
... Genetic studies suggest that genetic factors play an important role in the etiology of MDD and CMDs, with an estimated heritability of 31-42% in MDD (Sullivan et al. 2000), 30-60% in CAD (Marenberg et al. 1994) and 40-70% in obesity. Studies that aimed to estimate the genetic overlap between these conditions have revealed that MDD shares a genetic component of 42% with heart disease (Scherrer et al. 2003), 19% with hypertension (Scherrer et al. 2003) and 12% with obesity (Afari et al. 2010). In our recent systematic review of genome-wide and candidate gene studies, we found 24 shared genes and signaling pathways that could partly account for the comorbidity between CMDs and MDD, and that also may affect the effectiveness of treatments for these disorders (Amare et al. 2017a, b). ...
... 26,27 ETS included twin pairs who were born between 1946 and 1956, and excluded twin pairs if either member of the twin pair self-reported a history of CVD on the basis of previous survey data obtained by the registry in 1990. 28,29 Twin pairs discordant for depression or posttraumatic stress disorder were oversampled. At the baseline visit, conducted between 2002 and 2010, HRV was measured using 24-hour electrocardiographic monitoring. ...
Background
Autonomic function can be measured noninvasively using heart rate variability (HRV), which indexes overall sympathovagal balance. Deceleration capacity (DC) of heart rate is a more specific metric of vagal modulation. Higher values of these measures have been associated with reduced mortality risk primarily in patients with cardiovascular disease, but their significance in community samples is less clear.
Methods and Results
This prospective twin study followed 501 members from the VET (Vietnam Era Twin) registry. At baseline, frequency domain HRV and DC were measured from 24‐hour Holter ECGs. During an average 12‐year follow‐up, all‐cause death was assessed via the National Death Index. Multivariable Cox frailty models with random effect for twin pair were used to examine the hazard ratios of death per 1‐SD increase in log‐transformed autonomic metrics. Both in the overall sample and comparing twins within pairs, higher values of low‐frequency HRV and DC were significantly associated with lower hazards of all‐cause death. In within‐pair analysis, after adjusting for baseline factors, there was a 22% and 27% lower hazard of death per 1‐SD increment in low‐frequency HRV and DC, respectively. Higher low‐frequency HRV and DC, measured during both daytime and nighttime, were associated with decreased hazard of death, but daytime measures showed numerically stronger associations. Results did not substantially vary by zygosity.
Conclusions
Autonomic inflexibility, and especially vagal withdrawal, are important mechanistic pathways of general mortality risk, independent of familial and genetic factors.
... A French study of the elderly in the community revealed that hypertension was associated with anxiety but not depression [25]. On the other hand, a longitudinal study of 6903 male-male twins showed that hypertension was associated with depression, suggesting that there are common genetic factors that predispose individuals to hypertension and depression [26]. ...
Background: Depression is the most common geriatric psychiatric disorder. Other than organic, socio-demographic factors, substance use and co-morbidities have been found to play an important role in mental health. Objectives 1.To estimate proportion of depression among elderly OPD attendees. 2.To find out association between certain socio-demographic factors, substance use and co-morbidities with depression. Materials and Methods: Patients aged 60 years and older attending the Urban health training center during the period February-April of 2013 were included in the study. Geriatric depression scale 15 (GDS 15) was used to assess depression through face to face interviews and GDS score >7 was used as cutoff value for depression. Results: Total 73 participants were included in the study. The proportion of depression was 16% (95% CI:7.7-25.1). Statistically significant association was found with education, tobacco use, alcohol consumption and hypertension. Tobacco use and alcohol consumption were found as predictors of depression. Conclusion: Screening for depression in elderly in primary care setting is feasible. Taking history regarding tobacco and alcohol use may give a clue regarding underlying depression in these patients in primary care settings.
... The Emory Twin Study [22,23] included twins selected from the Vietnam Era Twin (VET) Registry, a large national sample of adult male twins who served on active duty during the Vietnam war era (1964)(1965)(1966)(1967)(1968)(1969)(1970)(1971)(1972)(1973)(1974)(1975) [24]. Participants in the initial visit, completed between 2002 and 2010, included 283 monozygotic (MZ) and dizygotic (DZ) twin pairs where at least one member of the pair had PTSD or major depression along with control pairs without these conditions; twin pairs were excluded if either member of the pair had a history of cardiovascular disease at the baseline survey [25]. Of these, 275 twins completed the in-person second evaluation and had complete PET cardiac imaging data, as previously detailed [22]. ...
Background
Obstructive sleep apnea (OSA) has been associated with incidence of cardiovascular disease and with nocturnal angina, but evidence of a link with coronary atherosclerosis and myocardial ischemia is limited and previous studies may have been affected by selection bias or unmeasured confounding factors.
Methods
We performed overnight polysomnography in 178 older male twins. The Apnea/Hypopnea Index (AHI) was calculated to assess OSA from the overnight sleep evaluation. AHI ≥15 was used as indicator of moderate/severe OSA. The following day, twins underwent myocardial perfusion imaging with [ ⁸² Rb]-chloride positron emission tomography. Quantitative and semiquantitative measures of myocardial perfusion and absolute myocardial blood flow were obtained.
Results
The mean age was 68 years and 40% of the sample had an AHI≥15, which indicates moderate to severe OSA. Abnormal myocardial perfusion, both with stress and at rest, was more common in twins with elevated AHI. After adjusting for clinical, lifestyle and behavioral factors, and previous history of cardiovascular disease, twins with AHI ≥15 had 3.6 higher odds (95% CI, 1.5–8.9) of an abnormal total severity score, defined as a score ≥100, and for each 5-point increment in AHI, the odds of abnormality increased by 20% (95% CI, 7%-34%). Twin pairs where both twins had OSA exhibited the greatest risk. There were no differences in measures of ischemia and absolute myocardial blood flow and flow reserve by AHI status.
Conclusions
OSA is associated with myocardial perfusion abnormalities that suggest prior subclinical myocardial scarring or infarction. Early environmental factors that affect both twins equally may play a role and should be further explored.
... Associations between depression and medical diseases also reflect shared genetic influences. Approximately 30% to 40% of the variation in major depression is attributable to genetic factors (12), some of which may also influence risk for medical conditions including cardiovascular disease (13)(14)(15)(16), though findings are mixed (17,18). ...
Background:
Major depressive disorder (MDD) is a leading cause of disease-associated disability, with much of the increased burden due to psychiatric and medical comorbidity. This comorbidity partly reflects common genetic influences across conditions. Integrating molecular-genetic tools with health records enables tests of association with the broad range of physiological and clinical phenotypes. However, standard phenome-wide association studies analyze associations with individual genetic variants. For polygenic traits such as MDD, aggregate measures of genetic risk may yield greater insight into associations across the clinical phenome.
Methods:
We tested for associations between a genome-wide polygenic risk score for MDD and medical and psychiatric traits in a phenome-wide association study of 46,782 unrelated, European-ancestry participants from the Michigan Genomics Initiative.
Results:
The MDD polygenic risk score was associated with 211 traits from 15 medical and psychiatric disease categories at the phenome-wide significance threshold. After excluding patients with depression, continued associations were observed with respiratory, digestive, neurological, and genitourinary conditions; neoplasms; and mental disorders. Associations with tobacco use disorder, respiratory conditions, and genitourinary conditions persisted after accounting for genetic overlap between depression and other psychiatric traits. Temporal analyses of time-at-first-diagnosis indicated that depression disproportionately preceded chronic pain and substance-related disorders, while asthma disproportionately preceded depression.
Conclusions:
The present results can inform the biological links between depression and both mental and systemic diseases. Although MDD polygenic risk scores cannot currently forecast health outcomes with precision at the individual level, as molecular-genetic discoveries for depression increase, these tools may augment risk prediction for medical and psychiatric conditions.
... As part of the ETSF we re-examined in person 279 twins (including 124 pairs and 31 singles) who had participated in the initial Emory Twin Study (ETS). [29,30] The ETS included twin pairs where at least one member had PTSD or major depression, and control pairs free of these psychiatric conditions based on information from previous registry surveys. Twins who self-reported any history of cardiovascular diseases according to 1990-1991 registry data were excluded from ETS. [28] The Sleep Substudy of the ETSF collected objective sleep measures among 230 twins (99 pairs, 32 singles). ...
Introduction: Sleep disturbance is associated with autonomic dysregulation, but the temporal directionality of this relationship remains uncertain. The objective of this study was to evaluate the temporal relationships between objectively measured sleep disturbance and daytime or nighttime autonomic dysregulation in a co-twin control study.
Methods: A total of 68 members (34 pairs) of the Vietnam Era Twin Registry were studied. Twins underwent 7-day in-home actigraphy to derive objective measures of sleep disturbance. Autonomic function indexed by heart rate variability (HRV) was obtained using 7-day ECG monitoring with a wearable patch. Multivariable vector autoregressive models with Granger causality tests were used to examine the temporal directionality of the association between daytime and nighttime HRV and sleep metrics, within twin pairs, using 7-day collected ECG data.
Results: Twins were all male, mostly white (96%), with mean (SD) age of 69 (2) years. Higher daytime HRV across multiple domains was bidirectionally associated with longer total sleep time and lower wake after sleep onset; these temporal dynamics were extended to a window of 48 h. In contrast, there was no association between nighttime HRV and sleep measures in subsequent nights, or between sleep measures from previous nights and subsequent nighttime HRV.
Conclusions: Daytime, but not nighttime, autonomic function indexed by HRV has bidirectional associations with several sleep dimensions. Dysfunctions in autonomic regulation during wakefulness can lead to subsequent shorter sleep duration and worse sleep continuity, and vice versa, and their influence on each other may extend beyond 24 h.
... Conversely, poor adherence to ICS caused by depression would increase the risk of death. Second, depression was associated with increased risk factors for mortality such as hypertension, cardiovascular disease, obesity, and type 2 diabetes [24][25][26]. Consistent with previous studies, we found that adults with asthma and depression were more likely to have obesity, hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, stroke, emphysema, chronic bronchitis, and cancer compared with those with asthma only. ...
Background
The relation between depression and mortality in patients with asthma is not well known. This study aimed to assess the impact of depression on mortality in asthmatic patients in US adults.
Methods
This observational study used data from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES). Depression was measured using the Patient Health Questionnaire-9 (PHQ-9). We used survey-weight adjusted Cox proportional hazard models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between depression and all-cause mortality.
Results
A total of 1865 participants with asthma were included in this study. Among them, 264 (14.16%) had depressive symptoms. During 9970 person-years of follow-up, there were 24 (9.1%) deaths in 264 patients with depression compared with 100 (6.3%) deaths in 1601 patients without depression. For unadjusted analyses, depression was associated with an increased risk of all-cause mortality (HR, 2.22 [95% CI 1.32–3.73]). This association was persistent after adjustment for age, sex, race/ethnicity, and body mass index (HR, 2.71 [95% CI 1.58–4.66]). However, we did not observe a significant association between depression and mortality after controlling for extensive co-morbidities (HR, 1.92 [95% CI 0.82–4.45]). Subgroup analyses further revealed that depression was an independent risk factor for mortality only in the females (HR, 3.78 [95% CI 1.17, 12.26]) but not all asthmatic patients.
Conclusions
The present study suggested that depressive disorder was common in asthmatic patients and depression in asthmatic patients was associated with a higher mortality rate. Depression was an independent risk factor for mortality in female patients.
... Dyslipidemia and lower level of plasma HDL were also reported to be associated with acute-phase schizophrenia [46]. Another index of metabolic syndromes, BP, was proposed to explain the associations between psychopathology and CVDs among patients with depressive symptoms while the direction of those associations was contradictory [47][48][49][50] and may be confounded by the use of antidepressants [51]. Pulse pressure was reported to be significantly correlated with cognitive impairment, which was a core feature of schizophrenia [52]. ...
Background
Patients with severe mental illness (SMI) and comorbid physical conditions were often associated with higher risks of mortality and hospital readmission. In this study, we aim to examine the association of cardiovascular metabolic risk factor measurements with risks of psychiatric readmissions among in-hospital patients with severe mental illness (SMI).
Methods
We collected the longitudinal information of laboratory investigations, blood pressure and body mass index (BMI) among in-hospital patients who had been diagnosed with schizophrenia, major depression disorder or bipolar disorder and with comorbid diagnosis of hypertension, hyperlipidemia or diabetes from Jan 2014 to Jan 2019. The primary outcome was time to first psychiatric readmission. Cox proportional hazard model was utilized to calculate the hazard risks (HR) of cardiovascular metabolic risk factors with psychiatric readmission.
Results
A total of 5,256 patients were included in the analysis. Compared to patients with normal blood parameters, patients with aberrant tests of high-density dyslipidemia (HDL) and diastolic blood pressure (DBP) during in-hospitalization period were associated with higher risks to first psychiatric readmission [ HR (Hazard Ratio), 1.37 95% Confidence interval (CI), 1.03–1.83 for HDL and HR, 1.32 (95% CI, 1.04–1.67])for DBP]. Compared to patients with optimal monitoring, patients with suboptimal monitoring of blood lipids and blood pressure during in-hospitalization period or recommended window period of cardiovascular disease (CVD) risk management were associated with higher risks to first psychiatric readmission.
Conclusions
Aberrant cardiovascular metabolic blood test and blood pressure and missing measurements among in-hospital patients with SMI were associated with increased risks of psychiatric readmissions. This calls for more active screening and monitoring of CVD risk factors for those in-hospital patients in need.
... This study focused on one facet, namely the hypothesis that a gene is associated with both blood pressure and anxious-depressed mood. The plausibility of this hypothesis is strengthened by heritability estimates of both blood pressure, depression and anxiety related disorders which range from 32%-60% [6,7], 25%-65% [8][9][10][11] and ~48% [12,13] respectively and a study [14] that estimated blood pressure and depression share 20% of their genetic variation. ...
Background: Depression and cardiovascular disease risk factors develop in childhood. The objective of this study was to investigate cross sectional and longitudinal associations between blood pressure, mood scores and tagged SNPs within the Monoamine oxidase A (MAOA) gene in the Western Australian Pregnancy Cohort (Raine) Study. Methods: Data from the five (n=1097), eight (n=1046), ten (n=1026) and fourteen (n=1124) year surveys were used. Blood pressure was measured at all surveys, anxious-depressed scores obtained from the Childhood Behavior Checklist at all surveys and depressive symptom scores from the Beck Depression Inventory for Youth at 14 years. Single nucleotide polymorphisms (SNPs) tagging the MAOA gene were identified from HapMap Phase II (CEU) data and genotyped. Cross sectional and longitudinal analyses were used to examine the association between blood pressure (outcome) and tagged SNPs within the MAOA gene and anxious/depressed scores (outcome) and tagged SNPs within the MAOA gene. Results: At 14 years, boys with the risk allele of SNP rs5905859 and rs3027396 had higher systolic blood pressure (βrs5905859=2.5; 95% CI: 0.743, 4.337 and βrs3027396=2.5; 95% CI: 0.681, 4.383 respectively) and lower mood scores (βrs5905859=-0.1; 95% CI: -0.100, -0.022 and βrs3027396=-0.2; 95% CI: -0.313,-0.045 respectively). Longitudinally, boys with the risk allele of SNPs rs5905859 (β=0.3; 95% CI: 0.026, 0.540) or rs6609257 (β= 0.3; 95% CI: 0.022, 0.521) had a higher mean systolic blood pressure trajectory compared to boys without. Conclusions: Variation within or close to the MAOA gene may explain in part the association between lower depressive symptom scores and higher systolic blood pressure in Caucasian boys within the Raine cohort.
... A longitudinal study of Korean men 60 reported that high alcohol consumption among men, compared with normal consumption, was associated with depression. With reference to health problems, a systematic review and meta-analysis study on obesity and depression revealed 61 that overweight and obesity were risk factors for depression among adults aged 20-59 years, and Scherrer et al 62 reported that cardiovascular disease is a risk factor of depression among middle-aged men. The Open access effect of exposure to childhood abuse on mental distress is partly mediated by other factors such as PTSD symptoms, 55 as PTSD occurs concomitant with other psychiatric disorders such as anxiety and depression. ...
Objectives
To estimate the prevalence of emotional, physical and sexual childhood abuse, and symptoms of post-traumatic stress disorder (PTSD) and to examine the association between childhood abuse and adult mental health problems, including mental distress and PTSD symptoms.
Design
A community-based cross-sectional study was conducted. Childhood abuse was assessed with the NorVold Abuse Questionnaire, and mental distress and symptoms of PTSD were measured using the Hopkins Symptom Checklist 10 and the Impact of Event Scale—Revised, respectively. The Wald test and multiple linear regression analysis were applied for testing differences between proportions and the association between childhood abuse and adult mental health outcomes, respectively.
Setting
Urban and rural areas of the Yangon Region, Myanmar.
Participants
A total of 2377 men and women aged 18–49 years were included. Institutionalised people, monks, nuns and individuals deemed too ill physically and/or mentally to participate were excluded.
Results
Overall, 21.1% (95% CI 18.8 to 23.6) reported any form of childhood abuse, 10.4% (95% CI 8.9 to 12.4) physical abuse, 10.4% (95% CI 8.8 to 12.2) emotional abuse and 7.3% (95% CI 5.7 to 9.3) sexual abuse. Childhood abuse was more common in women (29.8%) than in men (12.4%). The prevalence of PTSD symptoms in the total sample was 6.6%. After adjusting for confounding variables, positive associations were found between childhood abuse with adult mental distress and PTSD symptoms among women and older men.
Conclusions
Childhood abuse is prevalent among both men and women in the Yangon Region of Myanmar and associated with adult mental health problems. Approximately 7% of people report PTSD symptoms. It should prompt local health professionals and policy makers to establish prevention programmes to eliminate violence against children and to organise services for victims of childhood abuse. Care should be taken in generalising findings for less populated areas.
... For ETS, from VET Registry, we selected 283 MZ and DZ twin pairs (n = 566) born between 1946 and 1956 (representing 95% of all registry twins) who were discordant for depression or posttraumatic stress disorder (PTSD), as well as control pairs without these conditions. Twin pairs were excluded if either member of the twin pair had a history of cardiovascular disease at the baseline survey (21). Of the 283 ETS twin pairs, we invited 504 twins who were still alive (252 pairs) to participate in the Emory Twin Study Follow-up (ETSF) for a follow-up evaluation, in-person or over the phone (for those who were not able to travel), that was conducted on average 11.5 years after the initial ETS. ...
Objective:
Posttraumatic stress disorder (PTSD) has been related to accelerated biological aging processes, but objective evidence for this association is limited. DNA methylation (DNAm) age acceleration is a novel measure of biological aging which may help clarify if PTSD is related to biological aging processes. We aim to examine whether PTSD is associated with biological aging using a comprehensive set of DNAm age acceleration markers, and to what extent the unshared environment contributes to the association.
Methods:
Using a cross-sectional co-twin control study design, we investigated the association of the clinical diagnosis and symptom severity of posttraumatic stress disorder with six measurements of DNAm age acceleration based on epigenome-wide data derived from peripheral blood lymphocytes of 296 male twins from the Vietnam Era Twin Registry.
Results:
Twins with current PTSD had significantly advanced DNAm age acceleration compared with twins without PTSD for five out of six measures of DNAm age acceleration. Across almost all measures of DNAm age acceleration, twins with current PTSD were "epigenetically older" than their twin brothers without PTSD: estimated differences ranged between 1.6 (95% confidence interval 0.0 to 3.1) to 2.7 (95% confidence interval 0.5 to 4.8) biological age year-equivalents. A higher CAPS score was also associated with a higher within-pair DNAm age acceleration. Results remained consistent after adjustment for behavioral and cardiovascular risk factors.
Conclusions:
PTSD is associated with epigenetic age acceleration, primarily through unshared environmental mechanisms as opposed to genetic or familial factors. These results suggest that PTSD is related to systemic processes relevant to biological aging.
... An association study of 2,731 complete pairs of male-male twins which looked at the common genetic and environmental risk factors for depression, heart disease, and hypertension confirmed the co-occurrence of depression and cardiovascular disease, and found a significant genetic correlation between both depressive symptoms and hypertension (r=0.19) and also between depression and heart disease (r=0.42) (Scherrer, Xian et al. 2003). ...
http://deepblue.lib.umich.edu/bitstream/2027.42/79447/1/anapro.pdf
... Moreover, different types of surgery treatment may affect nutritional status and physical and emotional functioning. From a psychosomatic point of view, hypertension could be concomitant with depressive disorders (96). Depression might influence the occurrence and development of hypertension (97). ...
Background: Gastric cancer (GC) is one of the leading causes of death worldwide. It is associated with several disease-related impairments contributing to the psycho-social burden of those patients, such as deterioration of well-being and overall quality of life (QOL). The aim of this study is to present the wide range of factors potentially impacting patients' overall well-being and possible preventive interventions.
Methods: This systematic review was conducted in October 2020 with a search in the PubMed, MedLine, PsycInfo, and Google Scholar databases. We used the keywords “gastric cancer,” “gastric neoplasm,” and each of them combined with “quality of life,” “depression,” and “anxiety” to identify all relevant articles reporting about potential impact factors influencing the overall well-being of patients suffering from gastric cancer.
Results: Finally, 125,490 articles were found, of which 125,431 were excluded in several steps of screening. Inclusion criteria were studies carried out on human ≥18 years of age, studies in English or German language, clinical trials, registry-based studies, cohort studies, population-based studies, and certain titles and abstracts. After screening for eligibility 35 potential factors influencing overall well-being in patients with GC were identified and classified into 9 important categories: genetic condition, treatment method, blood markers, nutritional status, daily living, state of health, mental state, supportive care, and alternative treatment.
Conclusion: Since various factors are involved in the development of patients' overall well-being, timely treatment of psycho-social impairments by physicians and psychologists is of enormous importance. Preventing psycho-social burden by improving patients' QOL should be of high importance in the treatment regimen of patients with GC.
... ETSF conducted a second visit of the Registry twins who participated in the Emory Twin Study (ETS) [35,36]. ETS initially included 566 twins (283 pairs) born between 1946 and 1956, with no prior history of cardiovascular disease who were examined in person between 2002 and 2010 when their mean age was 55 years [37]. The study included twin pairs discordant for depression or posttraumatic stress disorder (PTSD) based on previous registry surveys, as well as controls free of these psychiatric conditions. ...
Background
Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design.
Purpose
To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance.
Methods
We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association.
Results
Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use.
Conclusions
Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing.
... For ETS, from VET Registry, we selected 283 MZ and DZ twin pairs (n = 566) born between 1946 and 1956 (representing 95% of all registry twins) who were discordant for depression or posttraumatic stress disorder (PTSD), as well as control pairs without these conditions. Twin pairs were excluded if either member of the twin pair had a history of cardiovascular disease at the baseline survey (21). Of the 283 ETS twin pairs, we invited 504 twins who were still alive (252 pairs) to participate in the Emory Twin Study Follow-up (ETSF) for a follow-up evaluation, in-person or over the phone (for those who were not able to travel), that was conducted on average 11.5 years after the initial ETS. ...
Background:
Little is known about the role of DNA methylation (DNAm) epigenetic age acceleration in cognitive decline. Using a twin study design, we examined whether DNAm age acceleration is related to cognitive decline measured longitudinally in persons without a clinical diagnosis of dementia.
Methods:
We studied 266 paired male twins (133 pairs) with a mean age of 56 years at baseline. Of these, 114 paired twins returned for a follow-up after an average of 11.5 years. We obtained six indices of DNAm age acceleration based on epigenome-wide data from peripheral blood lymphocytes. At both baseline and follow-up, we administered a battery of cognitive measures and constructed two composite scores, one for executive function and one for memory function. We fitted multivariable mixed regression models to examine the association of DNAm age acceleration markers with cognitive function within pairs.
Results:
In cross sectional analyses at baseline, there was no association between DNAm age acceleration and cognitive function scores. In longitudinal analyses, however, comparing twins within pairs, each additional year of age acceleration using the Horvath's method was associated with a 3% decline (95% CI, 1% to 5%) in the composite executive function score and a 2.5% decline (95% CI, 0.01% to 4.9%) in the memory function score. These results did not attenuate after adjusting for education and other risk factors.
Conclusions:
Middle-aged men who had older DNAm age relative to their brothers of the same demographic age, showed a faster rate of cognitive decline in the subsequent 11.5 years. These results point to the role of epigenetic modifications in cognitive aging.
... В частности, было установлено, что у каждого из этих заболеваний есть общие гены, отвечающие одновременно за развитие депрессии, артериальной гипертензии и ИБС. Иными словами, развитие депрессии и основных ССЗ отчасти детерминировано одними и теми же генетическими факторами [14]. ...
The prevalence of depressive disorders at the population level is from 2,5 to 10% among patients with coronary heart disease - 20%. The presence of depressive disorders in patients with coronary artery disease leads to hypersympathicotonia decrease vagal activity, endothelial dysfunction and blood coagulation system, weighing down the disease. The most significant theories of pathophysiological mechanism of increased mortality in patients with cardiovascular disease in combination with mood disorders are increased thrombus formation and disturbance of the autonomic regulation of heart rhythm.
... As common biological pathways may underlie both depression and cardiometabolic traits 5 , shared genetic factors have been proposed as one of the mechanisms contributing to the comorbidities. Studies have shown genetic overlap between depression and blood pressure, total cholesterol level, body mass index (BMI), and heart rate variability [6][7][8][9] . However, only a limited spectrum of cardiometabolic abnormalities was considered in previous studies. ...
Numerous studies have suggested associations between depression and cardiometabolic abnormalities or diseases, such as coronary artery disease and type 2 diabetes. However, little is known about the mechanism underlying this comorbidity, and whether the relationship differs by depression subtypes. Using the polygenic risk score (PRS) approach and linkage disequilibrium (LD) score regression, we investigated the genetic overlap of various depression-related phenotypes with a comprehensive panel of 20 cardiometabolic traits. GWAS results for major depressive disorder (MDD) were taken from the PGC and CONVERGE studies, with the latter focusing on severe melancholic depression. GWAS results on general depressive symptoms (DS) and neuroticism were also included. We also identified the shared genetic variants and inferred enriched pathways. In addition, we looked for drugs over-represented among the top shared genes, with an aim to finding repositioning opportunities for comorbidities.
We found significant polygenic sharing between MDD, DS and neuroticism with various cardiometabolic traits. In general, positive polygenic associations with CV risks were observed for most depression phenotypes except MDD-CONVERGE. Counterintuitively, PRS representing severe melancholic depression was associated with reduced CV risks. Enrichment analyses of shared SNPs revealed many interesting pathways, such as those related to inflammation, that underlie the comorbidity of depressive and cardiometabolic traits. Using a gene-set analysis approach, we also revealed a number of repositioning candidates, some of which were supported by prior studies, such as bupropion and glutathione. Our study highlights shared genetic bases of depression with cardiometabolic traits, and suggests the associations vary by depression subtypes. To our knowledge, this is the also first study to make use of human genomic data to guide drug discovery or repositioning for comorbid disorders.
... A possible explanation of the relationship between lower BP and increasing risk of depression is that chronic symptoms observed in hypotension such as weakness, fatigue and dizziness could lead to psychological stress and subsequent depression (Wessely et al., 1990;Pilgrim et al., 1992). In addition, the genetic correlation of depression with hypertension is estimated to be 19% (Scherrer et al., 2003), suggesting the influence of pleiotropic genes and shared biological pathways among them. Future studies that assess these factors will be required to elucidate the mechanism underlying the inverse association between BP and incident depression. ...
Aims
To evaluate the bidirectional relationship between blood pressure (BP) and depressive symptoms using a large prospective cohort study.
Methods
Prospective cohort study was performed in 276 244 adults who participated in a regular health check-up and were followed annually or biennially for up to 5.9 years. BP levels were categorised according to the 2017 American College of Cardiology and American Heart Association hypertension guidelines. Depressive symptoms were assessed using Centre for Epidemiologic Studies-Depression (CESD) questionnaire and a cut-off score of ≥25 was regarded as case-level depressive symptoms.
Results
During 672 603.3 person-years of follow-up, 5222 participants developed case-level depressive symptoms. The multivariable-adjusted hazard ratios (HRs) [95% confidence interval (CI)] for incident case-level depressive symptoms comparing hypotension, elevated BP, hypertension stage 1 and hypertension stage 2 to normal BP were 1.07 (0.99–1.16), 0.93 (0.82–1.05), 0.89 (0.81–0.97) and 0.81 (0.62–1.06), respectively ( p for trend <0.001). During 583 615.3 person-years of follow-up, 27 787 participants developed hypertension. The multivariable-adjusted HRs (95% CI) for incident hypertension comparing CESD 16–24 and ⩾25 to CESD < 16 were 1.05 (1.01–1.11) and 1.12 (1.03–1.20), respectively ( p for trend <0.001) and in the time-dependent models, corresponding HRs (95% CI) were 1.12 (1.02–1.24) and 1.29 (1.10–1.50), respectively ( p for trend <0.001).
Conclusions
In this large cohort study of young and middle-aged individuals, higher BP levels were independently associated with a decreased risk for developing case-level depressive symptoms and depressive symptoms were also associated with incident hypertension. Further studies are required to elucidate the mechanisms underlying the bidirectional association between BP levels and incident depression.
... The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) [6] defined MS as the presence of at least three of the following: abdominal obesity, elevated triglyceride (TG) levels, decreased highdensity lipoprotein cholesterol (HDL-C) levels, hypertension, and hyperglycemia. Previous studies have reported associations between depression and several MS components, including larger waist circumference [1,3,7]; higher levels of glucose [7,8], blood lipids [9,10], and TG [1,3]; higher blood pressure (BP) [1,11,12]; and lower HDL-C levels [1,3]. Accumulating evidence suggests that depression is not simply a comorbidity of MS. ...
Background:
Depression shows different patterns depending on socioeconomic status (SES) and metabolic syndrome (MS). However, the nature of this association remains poorly understood. The aim of this study was to examine whether the combination of MS and lower SES was associated with the prevalence of depression, based on data from the Korea National Health and Nutrition Examination Survey (KNHANES).
Methods:
Data were obtained from a cross-sectional study of 24,102 adults (> 19 years of age) who participated in the KNHANES during 2008-2013 and for whom MS and depression data were available. MS was defined using the diagnostic criteria of the modified National Cholesterol Education Program Adult Treatment Panel III. Measure of depression was ascertained from self-reports of physician diagnosis. Multiple logistic regression analysis was used to evaluate the association between depression and MS as well as SES (alone and in combination).
Results:
Overall, 622 of the 24,102 subjects (2.6%) met the criteria for depression. The prevalence of depression was associated with MS, a lower high-density lipoprotein cholesterol level, an elevated triglyceride level, a lower education level, and a lower household income. Participants with MS and a low SES had a higher likelihood of depression than those without MS and a high SES (odds ratio [OR] = 4.180 for low education level and OR = 3.994 for low household income level).
Conclusions:
This study suggests that the combination of SES and MS may play an important role in depression, which has implications for healthcare policy and depression management.
... 215 It is also possible that there is a core biological pathway that leads to both depression and CHD, as suggested by twin studies showing a common genetic vulnerability between these two phenotypes. 212,216 Additional work has suggested shared, genetically influenced biological pathways underlying the association between depression and CHD that involve autonomic function, 217 inflammation, 218,219 and the serotoninergic system. 158 Patients with depression also show distinct patterns of DNA methylation that are also associated with an increase in inflammatory markers, suggesting epigenetics as another pathway by which core biological changes may lead to both disorders. ...
... The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) [6] defined MS as the presence of at least three of the following: abdominal obesity, elevated triglyceride (TG) levels, decreased highdensity lipoprotein cholesterol (HDL-C) levels, hypertension, and hyperglycemia. Previous studies have reported associations between depression and several MS components, including larger waist circumference [1,3,7]; higher levels of glucose [7,8], blood lipids [9, 10], and TG [1,3]; higher blood pressure (BP) [1,11,12]; and lower HDL-C levels [1,3]. Accumulating evidence suggests that depression is not simply a comorbidity of MS. ...
Background: Depression shows different patterns depending on socioeconomic status (SES) and metabolic syndrome (MS). However, the nature of this association remains poorly understood. The aim of this study was to examine whether the combination of MS and lower SES was associated with the prevalence of depression, based on data from the Korea National Health and Nutrition Examination Survey (KNHANES).
Methods: Data were obtained from a cross-sectional study of 24,102 adults (>19 years of age) who participated in the KNHANES during 2008–2013 and for whom MS and depression data were available. MS was defined using the diagnostic criteria of the modified National Cholesterol Education Program Adult Treatment Panel III. Measure of depression was ascertained from self-reports of physician diagnosis. Multiple logistic regression analysis was used to evaluate the association between depression and MS as well as SES (alone and in combination).
Results: Overall, 622 of the 24,102 subjects (2.6%) met the criteria for depression. The prevalence of depression was associated with MS, a lower high-density lipoprotein cholesterol level, an elevated triglyceride level, a lower education level, and a lower household income. Participants with MS and a low SES had a higher likelihood of depression than those without MS and a high SES (odds ratio [OR]=4.180 for low education level and OR=3.994 for low household income level).
Conclusions: This study suggests that the combination of SES and MS may play an important role in depression, which has implications for healthcare policy and depression management.
... triglyceride (TG) levels, decreased high-density lipoprotein cholesterol (HDL-C) levels, hypertension, and hyperglycemia. Previous studies have reported associations between depression and several MS components, including larger waist circumference [1,3,5]; higher levels of glucose [5,6], blood lipids [7,8], and TG [1,3]; higher blood pressure (BP) [1,9,10]; and lower HDL-C levels [1,3]. ...
Background: Accumulating evidence supports the existence of a metabolic–mood syndrome. Lower socioeconomic status (SES) is correlated with a higher prevalence of both depression and metabolic syndrome (MS). However, the nature of this association remains poorly understood. The objective of this study was to examine whether the combination of MS and lower SES was associated with the prevalence of depression.
Methods: We conducted a cross-sectional study of 24,102 adults (>19 years of age) who participated in the 2008–2013 Korean National Health and Nutrition Examination Survey and for whom MS and depression data were available. MS was defined using the diagnostic criteria of the modified National Cholesterol Education Program Adult Treatment Panel III. Depression was assessed using a questionnaire. Multiple logistic regression analysis was used to evaluate the association between depression and MS as well as SES (alone and in combination).
Results: Overall, 622 of the 24,102 subjects (2.2%) met the criteria for depression. The prevalence of depression was associated with MS, a lower high-density lipoprotein cholesterol level, an elevated triglyceride level, a lower education level, and a lower household income. Participants with MS and a low SES had a higher likelihood of depression than those without MS and a high SES (odds ratio [OR]=4.180 for low education level and OR=3.994 for low household income level).
Conclusions: This study suggests that the combination of SES and MS may play an important role in depression, which has implications for healthcare policy and depression management.
... Many of these stress circuitry regions are morphologically and functionally sexually dimorphic beginning in prenatal development [13][14][15][16][17][18], which we and others have shown predispose for sex differences in the susceptibility for mental disorders and increased risk for cardiovascular disease [2,7,8,19,20]. For example, women have twice the risk of men for developing comorbidity of depression and cardiometabolic disorders [21][22][23][24][25][26][27] leading to a 3-5-fold risk of death from heart disease in depressed women. ...
Cardiac autonomic dysregulation has been implicated in the comorbidity of major psychiatric disorders and cardiovascular disease, potentially through dysregulation of physiological responses to negative stressful stimuli (here, shortened to stress response). Further, sex differences in these comorbidities are substantial. Here, we tested the hypothesis that mood- and sex-dependent alterations in brain circuitry implicated in the regulation of the stress response are associated with reduced peripheral parasympathetic activity during negative emotional arousal. Fifty subjects (28 females) including healthy controls and individuals with major depression, bipolar psychosis and schizophrenia were evaluated. Functional magnetic resonance imaging and physiology (cardiac pulse) data were acquired during a mild visual stress reactivity challenge. Associations between changes in activity and functional connectivity of the stress response circuitry and variations in cardiovagal activity [normalized high frequency power of heart rate variability (HFn)] were evaluated using GLM analyses, including interactions with depressed mood and sex across disorders. Our results revealed that in women with high depressed mood, lower cardiovagal activity in response to negative affective stimuli was associated with greater activation of hypothalamus and right amygdala and reduced connectivity between hypothalamus and right orbitofrontal cortex, amygdala, and hippocampus. No significant associations were observed in women with low levels of depressed mood or men. Our results revealed mood- and sex-dependent interactions in the central regulation of cardiac autonomic activity in response to negative affective stimuli. These findings provide a potential pathophysiological mechanism for previously observed sex differences in the comorbidity of major depression and cardiovascular disease.
... Based on 130 twin pairs in the LSADT and MADT in whom both twins were diagnosed with ischemic heart disease. (24) 505 (26) 488 (25) 35 (14) Body mass index, median (IQR) 25 (22)(23)(24)(25)(26)(27) 25 (22)(23)(24)(25)(26)(27) 24 (22)(23)(24)(25)(26)(27) 23 (20)(21)(22)(23)(24)(25)(26) Self-reported hypertension, N (%) 496 (19) 334 (17) 350 (18) 37 (15) Self-reported diabetes, N (%) ...
Objective:
Individuals with mood disorders have increased risk of cardiovascular disease. The aims of this study were to evaluate if the risk of cardiovascular disease in individuals with mood disorder could be explained by shared genetic and early environmental factors.
Methods:
We included 6,714 Danish middle and old aged twins from two large population-based studies. Cox proportional hazards regression was used to perform individual-level and intra-pair analyses of the association between self-reported depression symptomatology scores and register-based diagnoses of ischemic heart disease.
Results:
Higher depression symptomatology scores (both total, affective and somatic) were associated with higher incidence of ischemic heart disease after multivariable adjustment in individual-level analyses. In intra-pair analyses, this association was similar but with slightly larger confidence intervals. There was no interaction with gender and no major differences between mono- or dizygotic twins. Within twin pairs, the twin scoring highest on depressive symptoms developed ischemic heart disease more often or earlier than the lower scoring twin. A sensitivity analysis including a 2-year time lag of depression symptomatology to limit the risk of reverse causality showed similar results.
Conclusion:
Genetic factors and early life environment do not seem to explain the association between depressive mood and ischemic heart disease. This article is protected by copyright. All rights reserved.
... Близнецовым методом выявлена ассоциация заболеваний сердца и артериальной гипертензии с симптомами депрессии, что, по мнению J.F. Scherrer и соавт. [15], предполагает общий генетический вклад, а не простое влияние общих факторов среды. ...
The review presents data on cognitive processes of emotional regulation, which are the result of the interaction of the activity of the prefrontal cortex and emotional centers, as the most important pathogenetic link in the psychosomatic relations of depressive and cardiovascular diseases. The neuroanatomical substrate of emotional regulation is the connection between emotional and cognitive processes, which are carried out through bidirectional neuronal interactions between the neocortex and emotional centers. This connection allows emotional centers to modulate cortical activity, and cognitive centers, through descending cortical influences, to modulate the processing of emotions. At present, direct and indirect connections of the frontal cortex with the centers of the autonomic nervous system and its stimulating sympathetic and inhibitory parasympathetic influences have been confirmed. Pathogenetic links of emotional dysregulation include neurobiological and cognitive (rumination, fixation on negative information) processes. The pathophysiological mechanisms of depression and cardiovascular diseases have common links - the dysregulation of the metabolic, immunological and hypothalamus-pituitary-adrenal systems. The tendency to negative emotional response, the prevalence of negative emotions and alexithymia (low awareness of emotions) stand out as predictors of the development of both cardiovascular diseases and depression. Studies aimed at studying the typology and meaning of emotional dysregulation in various forms of psychopathological disorders in the aspect of comorbidity and psychosomatic relationships with somatic diseases can be fruitful in terms of finding new approaches to diagnosis and therapy.
... ETSF conducted a second visit of the Registry twins who participated in the Emory Twin Study (ETS) [35,36]. ETS initially included 566 twins (283 pairs) born between 1946 and 1956, with no prior history of cardiovascular disease who were examined in person between 2002 and 2010 when their mean age was 55 years [37]. The study included twin pairs discordant for depression or posttraumatic stress disorder (PTSD) based on previous registry surveys, as well as controls free of these psychiatric conditions. ...
Introduction: Sleep apnea is exceedingly common in elderly men and is associated with higher risk of cardiovascular disease. Post-traumatic stress disorder (PTSD) and depression have been shown to be associated with sleep apnea, however results have not been consistent, and it is unclear whether this association is confounded by cardiovascular and behavioral risk factors. In this study, our objective was to explore the risk factors for sleep apnea with a focus on psychiatric history, and we hypothesized that the association of sleep apnea with psychiatric history can be largely influenced by cardiovascular and behavioral factors.
Methods: This was a cross-sectional analysis of 100 members of the Vietnam Era Twin (VET) Registry (50 twin pairs, mean age=68; range: 61-71 years). All twins underwent a one night in-lab polysomnography (PSG) to assess the apnea/hypopnea index (AHI). Clinical diagnoses of lifetime history of major depression and PTSD were obtained with the Structured Clinical Interview for DSM V (SCID); we also measured current depressive symptoms with the Beck Depression Inventory-II (BDI-II). To assess associations of study variables with AHI, within-pair differences in multivariable mixed-effects regression models were examined and β coefficients were calculated. In addition to lifetime history of depression and PTSD, we included in the model the following variables previously reported in the literature to be associated with AHI: body mass index (BMI), current smoking, history of alcohol abuse, and physical activity assessed with the Baecke score. Other variables included years of education, sedative/hypnotic use, and antidepressant use.
Results: The mean AHI among these men was 15.5 [SD=16.1]. A total of 18 and 28 twins had diagnoses of lifetime history of depression and PTSD, respectively. In bivariate analysis without adjustment for covariates, psychiatric history (depression or PTSD) was not significantly associated with higher AHI. In mixed-effects multivariable regression analysis, only higher BMI (β=2.3, 95% CI=1.5, 3.1) and less education (β=-1.3, 95% CI=-2.4, -0.1) were independently associated with higher AHI. Psychiatric history of depression (β=3.9, 95% CI=-3.5, 11.3) or PTSD (β=6.0, 95% CI=-0.9, 12.9) were not significantly associated with AHI. Additional analyses examining number of depressive symptoms (BDI-II) showed similar results.
Conclusion: As expected, higher BMI was associated with higher AHI, but several other variables thought to be associated with higher AHI were not confirmed, such as smoking status, alcohol abuse, sedative/hypnotic use, and lack of physical activity. In contrast to the prevailing literature, neither lifetime history of depression nor PTSD were associated with sleep apnea. However, the role for poor sleep quality other than sleep-disordered breathing still remains to be investigated.
... The heart is one of the important organs directly damaged by hypertension, and long-term cardiovascular hypertension leads to vascular remodeling, followed by gradual cardiac remodeling due to response to such chronic volume overload pressure, in which the left ventricular hypertrophy is the most significant. Such persistent remodeling will result in arrhythmia, and severe heart failure will cause sudden death (6,7). More than 30% of hypertension patients have ventricular remodeling in clinic. ...
The possibility of micro ribonucleic acid-29b (miR-29b) regulating blood pressure and cardiac function in the rat model of hypertension was investigated. Sixty rat models of hypertension were established and randomly divided into the lentivirus group (n=20), the negative lentivirus group (n=20) and the control group (n=20). Rats in the lentivirus group were injected with the recombinant lentivirus, and those in the negative lentivirus and control groups were injected with the negative control virus and infection enhancement solution, respectively. The systolic pressure of rats was monitored using the tail-cuff method, and changes in the cardiac function of rats were evaluated via high-frequency ultrasound. At 3 weeks after virus infection, rats were weighed and sacrificed, the heart was taken and the left ventricular mass index was calculated. Moreover, the expression of miR-29b in myocardial tissues was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The systolic pressure in the lentivirus group was significantly decreased compared with those in the negative lentivirus and control groups (P<0.05). In the lentivirus group, the systolic pressure was significantly reduced after virus transfection (P<0.05), and there were also statistically significant differences in ultrasonic measurement indexes (LVPWT, IVST, LVEDD and LVESD) (P<0.05). LVPWT was remarkably decreased at 5 weeks and 6 weeks compared with that in the previous week, and it was lower than those in the other two groups (all P<0.05). After virus transfection, IVST in the lentivirus group showed a decreasing trend, which was obviously lower than those in the other two groups (P<0.05). After virus transfection, LVEDD in the lentivirus group increased gradually, and was higher than that in the other two groups. The expression of miR-29b was upregulated in the lentivirus group compared with those in the other two groups (P<0.05). The overexpression of miR-29b can reduce the blood pressure and significantly improve the cardiac function of hypertension rats.
... As common biological pathways may underlie both depression and CM traits, shared genetic factors may possibly contribute to the comorbidities. Studies have shown genetic overlap between depression and blood pressure, total cholesterol level and body mass index (BMI) (Afari et al., 2010;Lopez-Leon et al., 2010;Scherrer et al., 2003). However, only a limited spectrum of CM abnormalities has been considered in previous studies. ...
1 Background
Numerous studies have suggested associations between depression and cardiometabolic (CM) diseases. However, little is known about the mechanism underlying this comorbidity, and whether the relationship differs by depression subtypes.
2 Methods
Using polygenic risk scores (PRS) and linkage disequilibrium (LD) score regression, we investigated the genetic overlap of various depression‐related phenotypes with a comprehensive panel of 20 CM traits. GWAS results for major depressive disorder (MDD) were taken from the PGC and CONVERGE studies, with the latter focusing on severe melancholic depression. GWAS results on general depressive symptoms (DS) and neuroticism were also included. We identified the shared genetic variants and inferred enriched pathways. We also looked for drugs over‐represented among the top‐shared genes, with an aim to finding repositioning opportunities for comorbidities.
3 Results
We found significant genetic overlap between MDD, DS, and neuroticism with cardiometabolic traits. In general, positive polygenic associations with CM abnormalities were observed except for MDD‐CONVERGE. Counterintuitively, PRS representing severe melancholic depression was associated with reduced CM risks. Enrichment analyses of shared SNPs revealed many interesting pathways such as those related to inflammation that underlie the comorbidity of depressive and CM traits. Using a gene‐set analysis approach, we also revealed several repositioning candidates with literature support (e.g., bupropion).
4 Conclusions
Our study highlights shared genetic bases of depression with CM traits, and suggests the associations vary by depression subtypes, which may have implications in targeted prevention of cardiovascular events for patients. Identification of shared genetic factors may also guide drug discovery for the comorbidities.
Abstract: Introduction: Head and neck cancer represents a prevalent global
health issue, with its incidence varying across different regions and correlating
with the presence of risk factors associated with these cancers. This study aimed
to assess the prognostic significance of key pre-treatment variables utilized in the
evaluation and management of head and neck carcinomas. Materials and
Methods: A prospective study was conducted on patients attending the outpatient
department. Inclusion criteria comprised biopsy-confirmed non-metastatic
carcinomas of the oral cavity, pharynx, and larynx, specifically squamous cell
carcinoma histology. Treatment protocols encompassed primary
chemoradiotherapy for pharyngeal cancers, followed by salvage surgery. Early
oral cavity cancers underwent either surgery alone or surgery followed by
adjuvant chemoradiotherapy, while locally advanced disease received surgery
followed by chemoradiotherapy. Results: Oral cavity cancers constituted the most
common site, followed by hypopharynx, oropharynx, and larynx. The majority of
patients presented with locally advanced stage IV and stage III disease. Early�stage head and neck cancers accounted for about 28% of cases. Most lesions
exhibited moderately differentiated carcinomas. Conclusion: Stratifying head
and neck cancer patients based on specific patient, tumor, and treatment-related
variables is feasible. Tumor stage, degree of differentiation, ECOG performance
status, treatment-related weight loss, and treatment interruption are identified as
prognostic factors influencing survival outcome
Coronary artery disease (CAD), type 2 diabetes (T2D) and depression are among the leading causes of chronic morbidity and mortality worldwide. Epidemiological studies indicate a substantial degree of multimorbidity, which may be explained by shared genetic influences. However, research exploring the presence of pleiotropic variants and genes common to CAD, T2D and depression is lacking. The present study aimed to identify genetic variants with effects on cross-trait liability to psycho-cardiometabolic diseases. We used genomic structural equation modelling to perform a multivariate genome-wide association study of multimorbidity (Neffective = 562,507), using summary statistics from univariate genome-wide association studies for CAD, T2D and major depression. CAD was moderately genetically correlated with T2D (rg = 0.39, P = 2e-34) and weakly correlated with depression (rg = 0.13, P = 3e-6). Depression was weakly correlated with T2D (rg = 0.15, P = 4e-15). The latent multimorbidity factor explained the largest proportion of variance in T2D (45%), followed by CAD (35%) and depression (5%). We identified 11 independent SNPs associated with multimorbidity and 18 putative multimorbidity-associated genes. We observed enrichment in immune and inflammatory pathways. A greater polygenic risk score for multimorbidity in the UK Biobank (N = 306,734) was associated with the co-occurrence of CAD, T2D and depression (OR per standard deviation = 1.91, 95% CI = 1.74-2.10, relative to the healthy group), validating this latent multimorbidity factor. Mendelian randomization analyses suggested potentially causal effects of BMI, body fat percentage, LDL cholesterol, total cholesterol, fasting insulin, income, insomnia, and childhood maltreatment. These findings advance our understanding of multimorbidity suggesting common genetic pathways.
Background:
Cardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease.
Methods:
We conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder.
Results:
Among 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94).
Conclusion:
Depression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.
RESUMEN: Con el propósito de evaluar la efectividad de la intervención breve en bebedores de riesgo en una población adulta joven de una zona urbana de Coro Falcón Venezuela se realizó un estudio descriptivo prospectivo de corte transversal, a una muestra de 52 personas que reunieron los criterios, se aplicó encuesta autoadministrada que recoge aspectos sociodemográficos y test AUDIT. Los bebedores en zona II audit. (8-15 pts) se les realizó intervención breve. Como resultado se obtuvo 31 % bebedores en zona II, de los cuales 57 % solteros, 100 % bebedores de cerveza, 22 % obreros y estudiantes, 43 % empleados, 44 % con grado de instrucción secundaria incompleta, 87 % con antecedentes de consumo familiar. En cuanto a la efectividad de la intervención breve al comparar los valores de audit. inicial y posterior se apreció una reducción del puntaje significativo (P< 0,0001) como hallazgo se encontraron diferencias significativas en el audit. inicial y control de los bebedores zona III y IV (P< 0,049) Se concluye que la intervención fue efectiva en los pacientes estudiados. Palabras clave: Intervención breve, AUDIT, bebedor de riesgo
Background: Understanding the genetic underpinnings of antidepressant treatment response in unipolar major depressive disorder (MDD) can be useful in identifying patients at risk for poor treatment response or treatment resistant depression. A polygenic risk score (PRS) is a useful tool to explore genetic liability of a complex trait such as antidepressant treatment response. Here, we review studies that use PRSs to examine genetic overlap between any trait and antidepressant treatment response in unipolar MDD.
Methods: A systematic search of literature was conducted in PubMed. Our search included studies examining associations between PRSs of psychiatric as well as non-psychiatric traits and antidepressant treatment response in patients with unipolar MDD. A quality assessment of the included studies was performed.
Results: In total, eleven articles were included which contained PRSs for 30 traits. Studies varied in sample size and endpoints used for antidepressant treatment response. Overall, PRSs for attention-deficit hyperactivity disorder, the personality trait openness, coronary artery disease, obesity, and stroke have been associated with antidepressant treatment response in patients with unipolar MDD.
Limitations: The endpoints used by included studies differed significantly, therefore it was not possible to perform a meta-analysis.
Conclusions: Associations between a PRS and antidepressant treatment response have been reported for a number of traits in patients with unipolar MDD. PRSs could be informative to predict antidepressant treatment response in this population, given advances in the field. Most importantly, there is a need for larger study cohorts and the use of standardized outcome measures.
Background
The joint effects of depressive symptoms and sleep on the risk of cardiovascular disease (CVD) are not well understood. The purpose of this study was to assess the combined impact of depressive symptoms and sleep duration on the incidence of CVD among middle-aged and older Chinese individuals.
Methods
Data were from the China Health and Longitudinal Study conducted in 2013, 2015, and 2018. A total of 9595 participants aged ≥45 years without a history of CVD in 2013 were included. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale (elevated depressive symptoms cutoff ≥10). Average sleep duration was self-reported. Logistic regression analyses adjusted for age, sex, marital status, education and other potential confounders were conducted.
Results
In total, 1072 (11.2%) participants reported CVD incidents over the 5-year period. Elevated depressive symptoms (OR=1.49, 95% CI=1.30-1.72) and short sleep duration (OR=1.21, 95% CI=1.05-1.40) were independently associated with an increased CVD risk in the fully adjusted model. Individuals with short sleep duration/low depressive symptoms (OR=1.34, 95% CI=1.12-1.60), short sleep duration/elevated depressive symptoms (OR=1.70, 95% CI=1.41-2.50), or long sleep duration/elevated depressive symptoms (OR=2.13, 95% CI=1.38-3.27) were more likely to develop CVD than those with normal sleep duration/low depressive symptoms.
Limitations
Depressive symptoms and sleep duration were self-reported.
Conclusions
A stronger risk of CVD was found when depressive symptoms and short or long sleep durations occurred together, suggesting that an integrated approach to sleep and depressive symptoms might be a feasible strategy for the prevention of CVD.
Background:
Depression occurs frequently in individuals with coronary artery disease (CAD) and is associated with a poor prognosis.
Objectives:
To determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression.
Search methods:
We searched the CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL databases up to August 2020. We also searched three clinical trials registers in September 2021. We examined reference lists of included randomised controlled trials (RCTs) and contacted primary authors. We applied no language restrictions.
Selection criteria:
We included RCTs investigating psychological and pharmacological interventions for depression in adults with CAD and comorbid depression. Our primary outcomes included depression, mortality, and cardiac events. Secondary outcomes were healthcare costs and utilisation, health-related quality of life, cardiovascular vital signs, biomarkers of platelet activation, electrocardiogram wave parameters, non-cardiac adverse events, and pharmacological side effects.
Data collection and analysis:
Two review authors independently examined the identified papers for inclusion and extracted data from the included studies. We performed random-effects model meta-analyses to compute overall estimates of treatment outcomes.
Main results:
Thirty-seven trials fulfilled our inclusion criteria. Psychological interventions may result in a reduction in end-of-treatment depression symptoms compared to controls (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.92 to -0.19, I2 = 88%; low certainty evidence; 10 trials; n = 1226). No effect was evident on medium-term depression symptoms one to six months after the end of treatment (SMD -0.20, 95% CI -0.42 to 0.01, I2 = 69%; 7 trials; n = 2654). The evidence for long-term depression symptoms and depression response was sparse for this comparison. There is low certainty evidence that psychological interventions may result in little to no difference in end-of-treatment depression remission (odds ratio (OR) 2.02, 95% CI 0.78 to 5.19, I2 = 87%; low certainty evidence; 3 trials; n = 862). Based on one to two trials per outcome, no beneficial effects on mortality and cardiac events of psychological interventions versus control were consistently found. The evidence was very uncertain for end-of-treatment effects on all-cause mortality, and data were not reported for end-of-treatment cardiovascular mortality and occurrence of myocardial infarction for this comparison. In the trials examining a head-to-head comparison of varying psychological interventions or clinical management, the evidence regarding the effect on end-of-treatment depression symptoms is very uncertain for: cognitive behavioural therapy compared to supportive stress management; behaviour therapy compared to person-centred therapy; cognitive behavioural therapy and well-being therapy compared to clinical management. There is low certainty evidence from one trial that cognitive behavioural therapy may result in little to no difference in end-of-treatment depression remission compared to supportive stress management (OR 1.81, 95% CI 0.73 to 4.50; low certainty evidence; n = 83). Based on one to two trials per outcome, no beneficial effects on depression remission, depression response, mortality rates, and cardiac events were consistently found in head-to-head comparisons between psychological interventions or clinical management. The review suggests that pharmacological intervention may have a large effect on end-of-treatment depression symptoms (SMD -0.83, 95% CI -1.33 to -0.32, I2 = 90%; low certainty evidence; 8 trials; n = 750). Pharmacological interventions probably result in a moderate to large increase in depression remission (OR 2.06, 95% CI 1.47 to 2.89, I2 = 0%; moderate certainty evidence; 4 trials; n = 646). We found an effect favouring pharmacological intervention versus placebo on depression response at the end of treatment, though strength of evidence was not rated (OR 2.73, 95% CI 1.65 to 4.54, I2 = 62%; 5 trials; n = 891). Based on one to four trials per outcome, no beneficial effects regarding mortality and cardiac events were consistently found for pharmacological versus placebo trials, and the evidence was very uncertain for end-of-treatment effects on all-cause mortality and myocardial infarction. In the trials examining a head-to-head comparison of varying pharmacological agents, the evidence was very uncertain for end-of-treatment effects on depression symptoms. The evidence regarding the effects of different pharmacological agents on depression symptoms at end of treatment is very uncertain for: simvastatin versus atorvastatin; paroxetine versus fluoxetine; and escitalopram versus Bu Xin Qi. No trials were eligible for the comparison of a psychological intervention with a pharmacological intervention.
Authors' conclusions:
In individuals with CAD and depression, there is low certainty evidence that psychological intervention may result in a reduction in depression symptoms at the end of treatment. There was also low certainty evidence that pharmacological interventions may result in a large reduction of depression symptoms at the end of treatment. Moderate certainty evidence suggests that pharmacological intervention probably results in a moderate to large increase in depression remission at the end of treatment. Evidence on maintenance effects and the durability of these short-term findings is still missing. The evidence for our primary and secondary outcomes, apart from depression symptoms at end of treatment, is still sparse due to the low number of trials per outcome and the heterogeneity of examined populations and interventions. As psychological and pharmacological interventions can seemingly have a large to only a small or no effect on depression, there is a need for research focusing on extracting those approaches able to substantially improve depression in individuals with CAD and depression.
Die hier vorliegende Arbeit beschäftigt sich mit dem Zusammenhang zwischen affektiven Störungen und dem kardiovaskulären Risiko. Besonderer Fokus lag dabei auf der Evaluation des Hypothalamus-Hypophysen-Nebennierenrinden-Systems bei depressiven Patienten. Kardiovaskuläre Erkrankungen stellen weltweit die führende Todesursache dar, während unipolare depressive Störungen insbesondere innerhalb der Industrieländer einen beträchtlichen Anteil der gesundheitsökonomischen Last bilden. Gemeinsam ist den Erkrankungen eine hohe und auf absehbare Zeit ansteigende Prävalenz, hinzukommt ein nicht unerheblicher Anteil an internistisch-psychiatrischer Komorbidität. So entwickeln kardiologische Patienten nach einem Myokardinfarkt bspw. häufig eine depressive Störung. Während dieser Einfluss somatischer Erkrankungen auf die psychische Gesundheit ausführlich untersucht ist, gilt dies für den umgekehrten nosologischen Zusammenhang nur eingeschränkt. Fest steht, dass depressive Patienten eine gegenüber Gesunden erhöhte Sterblichkeit aufweisen, die sich nicht allein auf Suizide, sondern allen voran auf ein schlechteres kardiovaskuläres Risikoprofil zurückführen lässt. So begünstigt das Vorliegen einer depressiven Störung die Entwicklung somatischer Pathologien wie z. B. des metabolischen Syndroms, was wiederum zu einer Erhöhung der Inzidenz artherosklerotischer Erkrankungen beiträgt. Neben behavioralen und inflammatorischen Prozessen scheint dabei v. a. dem Hypothalamus-Hypophysen-Nebennierenrinden-System eine entscheidende Mediator-Rolle zuzukommen. Bei diesem handelt es sich um ein komplexes endokrines System, das hauptsächlich im Rahmen des Stresserlebens zahlreiche Auswirkungen auf den Metabolismus besitzt und darüber hinaus enge Verknüpfungen zum autonomen Nervensystem sowie dem Immunsystem aufweist. Die Evaluation der Funktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems erfolgt anhand verschiedener Methoden, die jeweils spezifische Vor- und Nachteile besitzen und in ihrer Aussagekraft nicht als äquivalent anzusehen sind. Ein Konsens bzgl. des zur Untersuchung somatischer Folgeschäden bei depressiven Patienten vorrangig einzusetzenden Verfahrens besteht bislang nicht. Dies ist insofern von wissenschaftlicher Relevanz, als dass bei Patienten mit affektiven Störungen regelmäßig und in unterschiedlichem Ausmaß eine Überaktivierung des Stress-Systems z. B. in Form eines erhöhten Sympathikotonus oder einer Hypercortisolämie vorliegt, was mit diversen somatischen Folgeschäden in Verbindung gebracht wird/werden kann. So ließen sich einige Pathologien, die bei Patienten mit Cushing-Syndrom vorliegen, auch bei depressiven Patienten finden, z. B. eine viszerale Adipositas, ein reduziertes Volumen des Hippocampus sowie eine verringerte Knochendichte. In einer Pilotstudie konnte bei depressiven Patienten, die eine Dysfunktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems in Form einer Non-Suppressionsreaktion auf den Dexamethason-Hemmtest oder eine Hypercortisolämie aufwiesen, außerdem eine im Vergleich zu gesunden Kontrollen signifikante linksventrikuläre Hypertrophie festgestellt werden, die als eigenständiger Risikofaktor hinsichtlich der kardiovaskulären Mortalität gilt. Im Rahmen der dieser Arbeit zugrundeliegenden STRESSD HEART-Studie wurde daher an 57 Patienten, die sich aufgrund einer depressiven Episode im Zentralinstitut für Seelische Gesundheit Mannheim in Behandlung befanden, die Aktivität des Hypothalamus-Hypophysen-Nebennierenrinden-Systems evaluiert und die Auswirkung einer Funktionsstörung auf die linksventrikuläre Masse untersucht. Letztere wurde dabei echokardiographisch ermittelt. Im Hinblick auf die Funktion des Stresssystems erfolgte ein Methodenvergleich zwischen Dexamethason-Hemmtest, Messung der Cortisol-Ausscheidung über den Nachturin sowie einer abendlichen Cortisol-Bestimmung im Speichel. Die Prävalenz einer linksventrikulären Hypertrophie lag bei den untersuchten Probanden mit je nach verwendetem echokardiographischen Index 12 – 37 % deutlich höher als es bei einer vergleichbaren gesunden Population zu erwarten gewesen wäre. Die Werte für die linksventrikuläre Masse bei Non-Suppressoren betrugen dabei im Mittel 207 ± 73 g gegenüber 343 ± 97 g in der Pilotstudie. Das Vorliegen einer Hypertrophie korrelierte jedoch nur eingeschränkt mit den Parametern zur Evaluation des Hypothalamus-Hypophysen-Nebennierenrinden-Systems, sodass sich ein signifikanter Unterschied nur zwischen den Gruppen der Non-Suppressoren und Suppressoren fand, jedoch nicht in Bezug auf die nächtliche Cortisol-Ausscheidung über den Urin oder die Konzentration im Speichel. Auch der Zusammenhang zwischen gestörter Reaktion auf den Dexamethason-Hemmtest und linksventrikulärer Masse erreichte nach statistischer Kontrolle für das Alter und das Geschlecht nicht mehr das Signifikanzniveau. Mit Hilfe der multiplen linearen Regressionsanalyse konnte ein eigenständiger Einfluss der Reaktion auf den Dexamethason-Suppressionstest auf die linksventrikuläre Masse dementsprechend nicht festgestellt werden. Für den Blutdruck ließ sich jedoch ein solcher Einfluss nachweisen, was auch nach Kontrolle für die Variablen Alter, Geschlecht sowie BMI Bestand hatte. Der Methodenvergleich der verschiedenen Parameter zur Evaluation des Hypothalamus-Hypophysen-Nebennierenrinden-Systems ergab insgesamt unterschiedlich starke Korrelationen. So wiesen insbesondere die Cortisol-Bestimmungen im Speichel nur eine schwache Assoziation zu den übrigen Methoden und keine Assoziation zu somatischen Parametern auf. Die nächtliche Cortisol-Ausscheidung über den Urin korrelierte hingegen stark und positiv mit dem Cortisol-Serumspiegel nach Dexamethason-Gabe und identifizierte bei einzelnen Probanden Dysfunktionen des Hypothalamus-Hypophysen-Nebennierenrinden-Systems, die im Dexamethason-Hemmtest eine unauffällige Reaktion gezeigt hatten. Zusammenfassend legen die Ergebnisse der Arbeit nahe, dass zum Zwecke einer Untersuchung des Zusammenhangs zwischen der Aktivität des Hypothalamus-Hypophysen-Nebennierenrinden-Systems und somatischen Folgeschäden eine Kombination aus DST mit anschließender Serum-Cortisol-Bestimmung und eine Messung des freien Cortisols im Nachturin erfolgen sollte, da letztere dazu geeignet zu sein scheint, einzelne Probanden mit gestörter Funktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems zu identifizieren, die im DST unerkannt bleiben. Mit Hinblick auf die Anwendung im klinischen Setting gehen diese Methoden mit spezifischen Vorteilen einher, so zeigen sich die nächtliche Urinsammlung sowie die Durchführung eines DST als Kurztest mit einmaliger Blutentnahme als günstige, gegenüber Störungen robuste und von Patienten gut akzeptierte Verfahren. Hinsichtlich des Vorliegens einer linksventrikulären Hypertrophie widersprechen die in der Arbeit vorgestellten Daten der Annahme der Pilotstudie. Zwar lag bei depressiven Patienten eine erhöhte Prävalenz für eine linksventrikuläre Hypertrophie vor, diese schien sich jedoch nur unter bestimmten Voraussetzungen zu entwickeln, sodass von einer klinisch relevanten Hypertrophie mit signifikanten Auswirkungen auf das kardiovaskuläre Risiko bei depressiven Patienten nur im Falle einer starken Dysfunktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems bei gleichzeitig vorliegender arterieller Hypertonie auszugehen sein dürfte. Diese Ergebnisse sind jedoch in Anbetracht der geringen Fallzahl der untersuchten Probanden mit Vorsicht zu betrachten.
Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. However, there is no animal study showing the direct relationship between ANGII and depression. To address this issue, ANGII-containing osmotic pumps were implanted into adult male C57BL/6 mice subcutaneously for subacute (7 days) and chronic (at least 21 days) periods and behavioral and molecular analyses were conducted. Chronic infusion of ANGII into mice induced depressive-like behaviors, including the tail suspension test and forced swimming test, which were reversed by imipramine. Chronic infusion of ANGII also induced microglial activation in the hippocampus with increase of Il-1β mRNA and decrease of Arg1 mRNA. In addition, chronic ANGII infusion activated the hypothalamic–pituitary–adrenal axis (HPA axis) and resulted in decreased hippocampal glucocorticoid receptor level. However, subacute ANGII infusion did not induce significant molecular and behavioral changes in mice compared to that of control. The molecular and behavioral changes by chronic ANGII infusion were reversed by co-treatment of minocycline or telmisartan. In addition, ANGII treatment also induced the pro-inflammatory changes in BV-2 microglial cells. Our results indicate that ANGII can induce depressive-like behaviors via microglial activation in the hippocampus and HPA axis hyperactivation in mice. These might suggest possible mechanism on depressive symptom in chronic hypertensive state.
In everyday practice, the doctor rarely encounters only one specific disease, more often a patient with comorbid pathology comes to him. Such a group of concomitant diseases are mental disorders. Their prevalence in cardiology practice reaches 80%. Mood affective, anxiety and somatization disorders, as well as cognitive impairment are observed most often. The review looked at mental disorders that occur in cardiac diseases with the highest number of deaths, such as coronary heart disease, including myocardial infarction and cardiac arrhythmias, arterial hypertension and cerebrovascular diseases. Including attention is paid to the senile asthenia syndrome, which is accompanied by cognitive impairment, loss of previous vital interests and depression. The review highlights the questions of regular and adequate psychopharmacotherapy of cardiovascular diseases, which leads to a statistically significant decrease in the frequency of their exacerbations, which reduces the number of doctors who come to see for somatogenic symptoms, and also allows to improve the prognosis of the underlying disease and significantly reduce mortality. It was observed that the doctor should take into account the fact that modern cardiological preparations have effects that can cause side effects in the form of mental disorders when choosing a therapy. Understanding the processes of formation and occurrence of mental diseases in a patient with cardiovascular pathology, as well as methods for their correction, can increase the effectiveness of the therapy and improve the prognosis of the underlying disease.
Aim: We explored the role of histone modification in the association of depression-hypertension by comparing norepinephrine transporter (NET) gene levels in different depression-hypertensive patients. Then, we analyzed the expression of NET correlation with inflammatory cytokines to provide a new direction for detecting the association mechanism between depression and hypertension.
Methods: NE expression levels in serum of diverse groups were detected by enzyme-linked immunosorbent assay. Then histone acetyltransferase (HAT), histone deacetylase (HDAC), H3K27ac, NET, TNF-α, and interleukin-6 (IL-6) were detected by western blot in nine female subjects in different depression and hypertension groups, and Chromatin immunoprecipitation-polymerase chain reaction (Chip-PCR) were used to confirm the degree of acetylation affecting on the transcription level of NET gene. Meanwhile, correlation between NET with TNF/IL-6 was analyzed by SPSS19.0 software program. Finally, Quantitative real-time polymerase chain reaction (qPCR) and western blot were used to detect TNF-α and IL-6 expression levels after NET overexpression or interference treatment in human umbilical vein endothelial cells and Neuro-2a cells.
Results: The expression of HAT and H3K27ac had lower levels in D-H and nonD-H group than nonD-nonH group. The results showed that higher acetylation could promote expression of NET genes. Meanwhile, the expression of NET had a significant negative correlation with IL-6 (R = −0.933, p < 0.01) and tumor necrosis factor (TNF) (R = −0.817, p < 0.01) in subjects. In addition, the results confirmed that TNF-α and IL-6 mRNA and protein partial expressions could be inhibited by NET in both HUVECs and Neuronal cells (p < 0.01).
Conclusion: In conclusion, differential expression of NET gene might function as an important factor in interaction between depression and hypertension by partially targeting TNF-α and IL-6.
Background
Depression often coexists with other chronic conditions in older people. The COACH study is an ongoing random controlled trial (RCT) to test the effectiveness of a primary-care-based collaborative care approach to treat co-morbid hypertension and depression in Chinese rural elders. In the COACH model, a team—village doctor (VD), aging worker (AW), and psychiatrist consultant—provides collaborative care to enrolled subjects in each intervention village for 12 months. This study examines how COACH was implemented and identifies facilitators and barriers for its more widespread implementation.
Methods
Five focus groups were conducted, two with VDs, two with AWs, and one with psychiatrists, for a total of 38 participants. Transcripts were analyzed using qualitative content analysis.
Results
COACH care-team members showed shared understanding and appreciation of the team approach and integrated management of hypertension and depression. Team collaboration was smooth. All members regarded COACH to be effective in reducing depressive symptoms and improving patient health. Facilitators to implementation include training, leaders’ support, geographic proximity between VD and AW pairs, preexisting relationships among care-team members, comparability of COACH activities and existing practices of VDs and AWs, and care team members’ caring about older members of their villages. Barriers to sustainability include frustration of some VDs related to their low wages and feelings of overload of some AWs.
Conclusions
COACH was positively perceived and successfully implemented. The findings offer guidance for planning primary-care-based collaborative depression care in low- and middle-income countries.
BACKGROUND: Psychosocial and socioeconomic factors have previously been associated with cardiovascular disease (CVD). I ask: 1) Are these associations causal? 2) Do their pathways overlap with one another? 3) Can they account for international differences in CVD? 4) Can they improve clinical risk prediction models? METHODS: Causality between education and coronary artery disease was investigated with Mendelian randomization analyses. For mediation and international differences, data on participants aged 45–69 years from the population-based HAPIEE cohort study were analysed using Cox regressions. A novel risk prediction model was derived from this data, and external validation was performed using data from the Estonian BioBank study. RESULTS: 1) Genetic predisposition towards longer education was associated with a reduction in coronary artery disease (Odds Ratio=0.67 [95% CI= 0.59 to 0.77], per extra 3.6 extra years of education), as well as large reductions in smoking. 2) In observational analyses, cardiovascular mortality was independently associated with unemployment, low material amenities, depression, being single, infrequent contacts with friends and relatives. These associations were of similar magnitude when comparing minimallyadjusted and fully-adjusted models. 3) International differences in CVD mortality between Russian & Central European cohorts remained unexplained after adjustment for conventional, psychosocial and socioeconomic risk factors. 4) Adding predominantly socioeconomic and psychosocial factors to risk prediction models improved their discrimination, clinical effectiveness, binary NRI and Net Benefit, in derivation and validation data. CONCLUSIONS: Education is probably a causal risk factor in the development of coronary heart disease. At least 6 socioeconomic/psychosocial factors appear to associate with CVD along pathways that may be relatively independent of one another and the conventional CVD risk factors. Uncovering their mechanisms may suggest novel avenues for intervention. While the causes of international differences in cardiovascular mortality remain unclear, socioeconomic and psychosocial factors substantially improved the performance of cardiovascular risk prediction.
Although depression aggregates in families, the degree to which this aggregation results from genetic vs environmental factors remains uncertain. We examined this question in 1033 female-female twin pairs from a population-based registry. Both members of each twin pair were "blindly" assessed by structured psychiatric interview. Nine commonly used definitions of major depression, which produced life-time prevalence rates ranging from 12% to 33%, were examined. For all definitions, the results of model fitting to twin correlations suggested that the liability to depression results from genetic factors and environmental experiences unique to the individual. For seven of the definitions, the estimated heritability of liability was similar, ranging from 33% to 45%. For the two definitions that included only primary cases of depression, the heritability was lower (21% to 24%). The results document that in women (1) genetic factors play a substantial, but not overwhelming, role in the cause of depression; (2) the tendency for depression to aggregate in families results largely from shared genetic and not from shared environmental factors; (3) except for definitions that exclude secondary cases, the magnitude of genetic influence is similar in broadly and narrowly defined forms of major depression; and (4) most environmental experiences of causative importance for depression are those not shared by members of an adult twin pair.
Genetic and environmental influences on insomnia were studied in 2,825 pairs of Vietnam era veteran male twins. The self-reported sleep problems studied included trouble falling asleep, trouble staying asleep, waking often, waking tired and a composite sleep scale. Twin correlations for each of the sleep problems were larger in monozygotic than in dizygotic pairs, with heritability estimates ranging from 0.21 to 0.42. There was no effect of common familial environment. Phenotypic correlations for combat experience and sleep problems were small, ranging from 0.00 to 0.09, with no differences seen in monozygotic and dizygotic twins. When the effects of genes and combat exposure were evaluated simultaneously, there was a significant genetic contribution to all sleep measures, but combat exposure was significantly associated only with overall sleep quality, waking often and having trouble staying asleep.
The hypothesis that a family history of myocardial infarction (MI) or primary cardiac arrest (PCA) is an independent risk factor for primary cardiac arrest was examined in a population-based case-control study. In addition, we investigated whether recognized risk factors account for the familial aggregation of these cardiovascular events.
PCA cases, 25 to 74 years old, attended by paramedics during the period 1988 to 1994 and population-based control subjects matched for age and sex were identified from the community by random digit dialing. All subjects were free of recognized clinical heart disease and major comorbidity. A detailed history of MI and PCA in first-degree relatives was collected in interviews with the spouses of case and control subjects by trained interviewers using a standardized questionnaire. For each familial relationship, there was a higher rate of MI or primary cardiac arrest (MI/PCA) in relatives of case compared with relatives of control subjects. Overall, the rate of MI/PCA among first-degree relatives of cardiac arrest patients was almost 50% higher than that in first-degree relatives of control subjects (rate ratio [RR]=1.46; 95% CI=1.23 to 1.72). In a multivariate logistic model, family history of MI/PCA was associated with PCA (RR=1.57; 95% CI=1.27 to 1.95) even after adjustment for other common risk factors.
Family history of MI or PCA is positively associated with the risk of primary cardiac arrest. This association is mostly independent of familial aggregation of other common risk factors.
Hypertension has been linked to several psychological factors, including depression, but the relation between hypertension incidence and depressive symptoms has not been adequately examined.
To determine if depressive symptoms independently predict hypertension incidence.
A prospective, multicenter, epidemiological cohort of young adults (aged 23-35 years at study entry) from the general community without hypertension followed up for 5 years.
A sample of 3343 adults from 4 urban areas stratified for race (black and white) from the CARDIA (Coronary Artery Risk Development in Young Adults) study.
Hypertension incidence, which was defined as blood pressure higher than 160/95 mm Hg (assessed on a single occasion) or the use of prescribed antihypertensive medication.
Participants with high scores (> or = 16) on the Center for Epidemiological Studies Depression (CES-D) Scale were at significant risk for hypertension incidence compared with those with low CES-D scores (< or =7; odds ratio, 2.10; 95% confidence interval, 1.22-3.61) after adjustment for other hypertension risk factors (eg, age, resting systolic blood pressure at the 5-year examination, physical activity, daily alcohol use, parental history of hypertension, education, presence of diabetes mellitus or heart disease, sex, and race) in fixed logistic models. Those with intermediate depressive symptoms (CES-D scores 8-15) were also at significant risk (adjusted odds ratio, 1.78; 95% confidence interval, 1.06-2.98). These associations were significant in blacks alone but were not found in whites, who had a lower hypertension incidence (29 [2%] of 1806) than blacks (89 [6%] of 1537).
Depressive symptoms were predictive of later hypertension incidence in young adults, and young blacks with depressive symptoms were at high risk of developing hypertension.
Psychosocial stressors have been shown to predict hypertension in several cohort studies; patterns of importance, sex differences, and interactions with standard risk factors have not been fully characterized.
Among 2357 adults in a population sample of Alameda County, California, free of hypertension in 1974, 637 reported in 1994 having ever used antihypertensive medication (27.9% of the men and 26.3% of the women). The effects of baseline psychosocial, behavioral, and sociodemographic factors on the incidence of treated hypertension were examined using multiple logistic regression.
Low education, African American race, low occupational prestige, worry about job stability, feeling less than very good at one's job, social alienation, and depressive symptoms each had significant (P<.05) age-adjusted associations with incident hypertension. Associations were weakened by adjustment for body mass index, alcohol consumption, smoking status, and leisure time physical activity, especially the associations of anomy and depression, which persisted in women but not in men. In multivariate models, job insecurity (odds ratio, 1.6), unemployment (odds ratio, 2.7), and low self-reported job performance (odds ratio, 2.1) remained independent predictors of hypertension in men, whereas low-status work (odds ratio, 1.3) was an independent predictor of hypertension in women.
In the general population, low occupational status and performance and the threat or reality of unemployment increase the likelihood of developing hypertension, especially among men, independent of demographic and behavioral risk factors. Psychological distress and social alienation may also increase hypertension incidence, especially in women, chiefly through an association with health risk behaviors.
To assess the validity of self-reported illnesses, medical records were reviewed for participants reporting major illnesses on the biennial follow-up questionnaires used in a prospective cohort study which began in 1976. In over 90% of cases of cancer of the breast, skin, large bowel, and thyroid, histopathology reports confirmed the subjects' self-report. Lower levels of confirmation were obtained for cancers of the lung, ovary, and uterus. Application of strict diagnostic criteria also gave lower levels of confirmation for myocardial infarction (68%) and stroke (66%). Among random samples of women reporting fractures and hypertension all records obtained confirmed self-reports. For self-reported elevated cholesterol levels 85.7% of self-reports were confirmed. Self-report is a valuable epidemiologic tool but may require additional documentation when the disease is diagnostically complex.
A Vietnam Era (1964-1975) Twin Registry of American male-male veterans born between 1939 and 1955 has been developed to provide a study sample for research evaluating the impact of Vietnam service on the medical and psychosocial aspects of health. In preparation for developing the Registry, several alternative sources of twins and methods for identifying twins were investigated. A computerized database of veterans discharged from the military after 1967 was selected as the source because it contains about 50% of the total Vietnam era veteran population, is reasonably unbiased, and provides a feasible method for identifying twins. Twins were identified using an algorithm which involved matching entries on the database for same last name, different first name, same date of birth, and similar social security number. Twin status was confirmed by review of military records. The registry, now complete, is composed of 7,400 twin pairs. It will be an important resource for future research projects.
Objectives:
To estimate the contribution of genes and shared family environment to the liability to DSM-IV major depression and to examine the influence of certain proband characteristics on twin concordance.Methods:
We studied 177 probands with major depressive disorder ascertained via the Maudsley Hospital Twin Register (London, England) and their same-sex cotwins. Diagnostic assessments were carried out blind to zygosity and information on the other member of the twin pair. Probandwise concordances were used to compute correlations in liability, and model fitting was performed using maximum likelihood procedures.Results:
The probandwise concordance was 46% in monozygotic (n=68) and 20% in dizygotic (n=109) twins, a statistically highly significant difference. There was no evidence of a sex difference in heritability or of shared environmental effects. Depending on the assumed population risks for DSM-IV, major depression estimates of heritability were between 48% and 75%. A duration of longest episode of less than 13 months, multiple episodes, and an endogenous rather than neurotic pattern of symptoms, as established by the International Classification of Diseases, Ninth Revision, in the proband were associated with a trend toward a higher monozygoticdizygotic concordance ratio. Using log-linear analysis, only the association between duration of episodes and monozygotic-dizygotic concordance ratio was significant.Conclusions:
Liability to DSM-IV major depression has a substantial heritable component, and there is no evidence of an effect of shared family environment. Some proband characteristics, especially shorter duration of episodes, may be associated with a larger degree of genetic determination.
Background: Depression affects more women than men and often aggregates in families. Using a communitybased sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied. Methods: A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting. Results: Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression. Conclusions: There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition. Arch Gen Psychiatry. 1999;56:557-563
Background
Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men.Research Methods
We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors.Results
The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56).Conclusions
In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.
Objective.
—To determine if the diagnosis of major depression in patients hospitalized following myocardial infarction (Ml) would have an independent impact on cardiac mortality over the first 6 months after discharge.Design.
—Prospective evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode. Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set.Setting.
—A large, university-affiliated hospital specializing in cardiac care, located in Montreal, Quebec.Patients.
—All consenting patients (N=222) who met established criteria for Ml between August 1991 and July 1992 and who survived to be discharged from the hospital. Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months. There were no age limits (range, 24 to 88 years; mean, 60 years). The sample was 78% male.Primary Outcome Measure.
—Survival status at 6 months.Results.
—By 6 months, 12 patients had died. All deaths were due to cardiac causes. Depression was a significant predictor of mortality (hazard ratio, 5.74; 95% confidence interval, 4.61 to 6.87; P=.0006). The impact of depression remained after control for left ventricular dysfunction (Killip class) and previous Ml, the multivariate significant predictors of mortality in the data set (adjusted hazard ratio, 4.29; 95% confidence interval, 3.14 to 5.44; P=.013).Conclusion.
—Major depression in patients hospitalized following an Ml is an independent risk factor for mortality at 6 months. Its impact is at least equivalent to that of left ventricular dysfunction (Killip class) and history of previous Ml. Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms.(JAMA. 1993;270:1819-1825)
Major depression is a common comorbid condition in patients with coronary heart disease (CHD). Although mild emotional distress may be a normal reaction to myocardial infarction or other manifestations of CHD, major depression should not be considered a normal reaction, nor should it be ignored. Major depression is a debilitating comorbid disorder that can seriously complicate recovery and increase the risks of further cardiac morbidity and mortality. Fortunately, it is one that can be successfully treated in the majority of cases. The purpose of this review is to present the evidence for the negative prognostic effects of depression in cardiac patients and to discuss methods for assessing and treating depression in these patients.
The equal-environments assumption (EEA) in twin studies of psychiatric disorders assumes that the family environment which contributes to risk for a disorder is equally correlated between monozygotic (MZ) and dizygotic (DZ) twin pairs. In a study of psychiatric disorders in female twins, Kendler and colleagues (1993) have demonstrated the utility of a test of the EEA which includes a specified family environmental factor defined by using measures of perceived zygosity. We tested the EEA assumption among 3155 male—male twin pair members of the Vietnam Era Twin Registry for the following DSM-III-R lifetime disorders: alcohol dependence, marijuana dependence, any illicit drug dependence, nicotine dependence, major depression, and posttraumatic stress disorder. The majority of MZ (81.6%; n = 1593) and DZ (90.2%; n = 1086) twin pairs agreed with the investigator''s assigned zygosity. The best-fitting model for each of these disorders did not allow for a specified family environmental influence. These results support the usefulness of perceived zygosity in tests of the EEA. In male twin pairs, perceived zygosity has little impact on twin similarity for common psychiatric disorders.
Background:
Depression affects more women than men and often aggregates in families. Using a community-based sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied.
Methods:
A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting.
Results:
Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs. women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression.
Conclusions:
There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition.
The information criterion AIC was introduced to extend the method of maximum likelihood to the multimodel situation. It was obtained by relating the successful experience of the order determination of an autoregressive model to the determination of the number of factors in the maximum likelihood factor analysis. The use of the AIC criterion in the factor analysis is particularly interesting when it is viewed as the choice of a Bayesian model. This observation shows that the area of application of AIC can be much wider than the conventional i.i.d. type models on which the original derivation of the criterion was based. The observation of the Bayesian structure of the factor analysis model leads us to the handling of the problem of improper solution by introducing a natural prior distribution of factor loadings.
The Vietnam Era Twin Registry consists of 4,774 male-male twin pairs born between 1939 and 1957 with both brothers having served in the United States military during the Vietnam War. The registry was originally developed to provide the best control group for Vietnam-exposed servicemen to study the long-term health consequences of service in Vietnam. Recognizing the potential value of the registry for other areas of medical research, the Department of Veterans Affairs in 1988 opened the registry for use by both VA and non-VA investigators. The existence of centralized VA data bases for deaths and VA hospitalizations will strengthen future followup of the twins. This article describes the characteristics of the registry population and the process for accessing the registry.
In order to evaluate the possibility of finding persons who have suffered a myocardial infarction (MI) by postal questionnaire, a self-administered questionnaire was sent to a random sample of 4400 men aged 45–64 years, drawn from the general population. The response rate was 95%. 176 men indicated that they had been hospitalized for MI, out of which 124 cases could be verified from medical records. Of the remaining men, 33 had evidence of cardiovascular disease (CVD) in their records but no MI, and 19 men had no evidence of CVD. The sensitivity (estimated from a subsample) was 100% and the specificity 98.7%. The predictive value was 100% for a negative response and 70.5% for a positive response.
The 33 positive responders whose MI could not be verified but who had evidence of CVD had characteristics fairly similar to the responders with verified Mis. However, the 19 positive responders whose MI could not be verified and who had no evidence of CVD had characteristics that were dissimilar from the MI group as well as from the negative responders.
The questionnaire thus identified all the MI cases. The need for validation can be limited to the relatively small group of positive responders.
The Vietnam Era Twin Registry (VETR) is a registry of 7375 American male veteran twin pairs born between 1939 and 1955 who served in the armed forces of the United States between 1964 and 1975. Optimal use of registry data requires the determination of zygosity. Two approaches are available: analysis of blood genetic marker systems and responses of twins to questions about sibling similarity. Zygosity for the VETR was determined using the questionnaire technique supplemented with blood group typing data abstracted from military records. After comparing four alternative zygosity assignment methods, a logistic regression technique which uses discriminating variables based on race was selected. The approach is similar to that described by Magnus et al. (1983) in their study of Norwegian twins, suggesting that questionnaire responses are independent of nationality and reinforcing the reliability of the questionnaire method for zygosity ascertainment.
Fifty-two patients undergoing cardiac catheterization and subsequently found to have significant coronary artery disease (CAD) were given structured psychiatric interviews before catheterization. Nine of these patients met criteria for major depressive disorder. All 52 patients were contacted 12 months after catheterization, and the occurrence of myocardial infarction, angioplasty, coronary bypass surgery and death was determined. Results of the study show that major depressive disorder was the best predictor of these major cardiac events during the 12 months following catheterization. The predictive effect was independent of the severity of CAD, left ventricular ejection fraction, and the presence of smoking. Furthermore, with the exception of smoking, there were no statistically significant differences between those patients with major depressive disorder and the remaining patients on any variable studied. The possible mechanisms relating major depressive disorder to subsequent cardiac events are discussed. It is concluded that major depressive disorder is an important independent risk factor for the occurrence of major cardiac events in patients with CAD.
A 16-year prospective study of a general population sample indicates that those who had reported a depression and/or anxiety disorder at baseline experienced 1.5 times the number of deaths expected on the basis of rates for a large reference population. As part of the Stirling County Study (Canada), the information was gathered from 1003 adults through structured interviews and was analyzed by means of a diagnostic computer program. The risk for mortality was assessed using external and internal standards, controlling for the effects of age and sex as well as for the presence of self-reported physical disorders at baseline. Increased risk was found to be significantly associated with affective but not physical disorders and with depression but not generalized anxiety. When this evidence about mortality was combined with information about subsequent psychiatric morbidity among survivors, 82% of those who were depressed at baseline had a poor outcome.
An examination of ascertainment bias in identification of twin pairs in the Vietnam Era Twin Registry has been conducted. A complete listing of all male-male Vietnam era veteran twin pairs born in Connecticut between 1939 and 1955 was obtained (N = 150). An attempt was made to match these pairs with a listing of Vietnam era veteran twin pairs derived from the United States Department of Defense's Defense Manpower Data Center (DMDC) computer files. The results indicate that the DMDC files identified only 46.7% of the 150 Connecticut born Vietnam era veteran pairs. Statistically significant differences (P less than 0.05) between pairs found on the DMDC files and Connecticut veteran pairs missing from the DMDC files are observed for the following variables: a) year of discharge from military service, b) total length of active military service, c) branch of service, and d) foreign service. No consistent pattern of bias is observed for factors related to the physical and psychosocial health of veteran pairs. The implications of the ascertainment biases in the Vietnam Era Twin Registry are discussed.
A Vietnam Era (1964-1975) Twin Registry of American male-male veterans born between 1939 and 1955 has been developed to provide a study sample for research evaluating the impact of Vietnam service on the medical and psychosocial aspects of health. In preparation for developing the Registry, several alternative sources of twins and methods for identifying twins were investigated. A computerized database of veterans discharged from the military after 1967 was selected as the source because it contains about 50% of the total Vietnam era veteran population, is reasonably unbiased, and provides a feasible method for identifying twins. Twins were identified using an algorithm which involved matching entries on the database for same last name, different first name, same date of birth, and similar social security number. Twin status was confirmed by review of military records. The registry, now complete, is composed of 7,400 twin pairs. It will be an important resource for future research projects.
The contributions of shared genes and shared environments to familial aggregation of coronary heart disease risk factors were investigated by genetic and epidemiologic analysis of 434 adult female twin pairs from the Kaiser-Permanente Twin Registry in Oakland, California, during 1978 and 1979. Initial estimates of genetic heritability were statistically significant for serum levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and Quetelet index, but were only marginally significant for systolic and diastolic blood pressures. These estimates were biased, however, because sisters in the same identical twin pair were more similar than sisters in the same fraternal twin pair not only with respect to shared genes but also with respect to shared environmental and behavioral influences. Heritability was estimated again after adjusting for shared environmental and behavioral effects by multiple regression analysis. Genetic heritability remained significant for HDL cholesterol (0.66), LDL cholesterol (0.88), triglycerides (0.53), and relative weight (0.55) but not for systolic (0.42) and diastolic (0.25) blood pressures. The strong genetic components of the levels of LDL cholesterol, HDL cholesterol, and relative weight may in part explain why some women have high levels of these coronary disease risk factors despite following recommended health behaviors.
To assess the validity of self-reported illnesses, medical records were reviewed for participants reporting major illnesses on the biennial follow-up questionnaires used in a prospective cohort study which began in 1976. In over 90% of cases of cancer of the breast, skin, large bowel, and thyroid, histopathology reports confirmed the subjects' self-report. Lower levels of confirmation were obtained for cancers of the lung, ovary, and uterus. Application of strict diagnostic criteria also gave lower levels of confirmation for myocardial infarction (68%) and stroke (66%). Among random samples of women reporting fractures and hypertension all records obtained confirmed self-reports. For self-reported elevated cholesterol levels 85.7% of self-reports were confirmed. Self-report is a valuable epidemiologic tool but may require additional documentation when the disease is diagnostically complex.
We first review the associations between depression and cardiovascular diseases (CVDs). Then we examine them in the nationally representative Mini-Finland Health Survey, which covers 8,000 persons. Chronic somatic diseases and mental disorders were diagnosed using standardized methods. Cross-sectionally, CVDs and neurotic depression were associated both before and after adjustment for covariates. The strongest associations were observed in the case of severe CVDs. During a 6.6 year follow-up, the risk of CVD death and coronary death was elevated in depressed persons both with and without CVDs at entry. Much of the cross-sectional association is probably due to depression caused by CVDs. The outcome of CVD may be poorer in depressed persons. The hypothesis that depression is a cause of CVDs requires further study.
A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins.
The study population consisted of 3298 monozygotic and 5964 dizygotic male twins and 4012 monozygotic and 7730 dizygotic female twins. The age at which one twin died of coronary heart disease was used as the primary independent variable to predict the risk of death from coronary heart disease in the other twin. Information about other risk factors was obtained from questionnaires administered in 1961 and 1963. Actuarial life-table analysis was used to estimate the cumulative probability of death from coronary heart disease. Relative-hazard estimates were obtained from a multivariate survival analysis.
Among the men, the relative hazard of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 years, as compared with the hazard when one's twin did not die before 55, was 8.1 (95 percent confidence interval, 2.7 to 24.5) for monozygotic twins and 3.8 (1.4 to 10.5) for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative hazard was 15.0 (95 percent confidence interval, 7.1 to 31.9) for monozygotic twins and 2.6 (1.0 to 7.1) for dizygotic twins. Among both the men and the women, whether monozygotic or dizygotic twins, the magnitude of the relative hazard decreased as the age at which one's twin died of coronary heart disease increased. The ratio of the relative-hazard estimate for the monozygotic twins to the estimate for the dizygotic twins approached 1 with increasing age. These relative hazards were little influenced by other risk factors for coronary heart disease.
Our findings suggest that at younger ages, death from coronary heart disease is influenced by genetic factors in both women and men. The results also imply that the genetic effect decreases at older ages.
Correlations between relatives were determined for systolic and diastolic blood pressure. The correlations decrease as age differences between relatives increase in a Norwegian sample with 43,751 parent-offspring pairs, 19,140 pairs of siblings, and 169 pairs of twins. A simple biometric model specifying only age-specific genetic additive effects and environmental effects fitted well to correlations between cotwins, pairs of siblings, and parent-offspring dyads in subsets of relatives grouped by age differences. None of the environmental effects appeared to be due to environmental factors that are shared by family members. Models that excluded a parameter for the age-specific genetic influence did not fit the data. The results may partly explain what seems to be a discrepancy between relatively low parent-offspring correlations from previous nuclear family studies and high correlations from twin studies, especially in identical twins.
To determine if the diagnosis of major depression in patients hospitalized following myocardial infarction (MI) would have an independent impact on cardiac mortality over the first 6 months after discharge.
Prospective evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode. Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set.
A large, university-affiliated hospital specializing in cardiac care, located in Montreal, Quebec.
All consenting patients (N = 222) who met established criteria for MI between August 1991 and July 1992 and who survived to be discharged from the hospital. Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months. There were no age limits (range, 24 to 88 years; mean, 60 years). The sample was 78% male.
Survival status at 6 months.
By 6 months, 12 patients had died. All deaths were due to cardiac causes. Depression was a significant predictor of mortality (hazard ratio, 5.74; 95% confidence interval, 4.61 to 6.87; P = .0006). The impact of depression remained after control for left ventricular dysfunction (Killip class) and previous MI, the multivariate significant predictors of mortality in the data set (adjusted hazard ratio, 4.29; 95% confidence interval, 3.14 to 5.44; P = .013).
Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months. Its impact is at least equivalent to that of left ventricular dysfunction (Killip class) and history of previous MI. Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms.
To estimate the contribution of genes and shared family environment to the liability to DSM-IV major depression and to examine the influence of certain proband characteristics on twin concordance.
We studied 177 probands with major depressive disorder ascertained via the Maudsley Hospital Twin Register (London, England) and their same-sex co-twins. Diagnostic assessments were carried out blind to zygosity and information on the other member of the twin pair. Probandwise concordances were used to compute correlations in liability, and model fitting was performed using maximum likelihood procedures.
The probandwise concordance was 46% in monozygotic (n = 68) and 20% in dizygotic (n = 109) twins, a statistically highly significant difference. There was no evidence of a sex difference in heritability or of shared environmental effects. Depending on the assumed population risks for DSM-IV, major depression estimates of heritability were between 48% and 75%. A duration of longest episode of less than 13 months, multiple episodes, and an endogenous rather than neurotic pattern of symptoms as established by the International Classification of Diseases, Ninth Revision, in the proband were associated with a trend toward a higher monozygotic-dizygotic concordance ratio. Using log-linear analysis, only the association between duration of episodes and monozygotic-dizygotic concordance ratio was significant.
Liability to DSM-IV major depression has a substantial heritable component, and there is no evidence of an effect of shared family environment. Some proband characteristics, especially shorter duration of episodes, may be associated with a larger degree of genetic determination.
Depression has been shown to adversely affect the prognosis of patients with established coronary artery disease, but there is comparatively little evidence to document the role of depression in the initial development of coronary disease.
Study participants were 409 men and 321 women who were residents of Glostrup, Denmark, born in 1914. Physical and psychological examinations in 1964 and 1974 established their baseline risk factor and disease status and their level of depressive symptomatology. Initial myocardial infarction (MI) was observed in 122 participants, and there were 290 deaths during follow-up, which ended in 1991. A 2-SD difference in depression score was associated with relative risks of 1.71 (P = .005) for MI and 1.59 (P < .001) for deaths from all causes. These findings were unchanged after we controlled for risk factors and signs of disease at baseline. There were no sex differences in effect sizes.
High levels of depressive symptomatology are associated with increased risks of MI and mortality. The graded relationships between depression scores and risk, long-lasting nature of the effect, and stability of the depression measured across time suggest that this risk factor is best viewed as a continuous variable that represents a chronic psychological characteristic rather than a discrete and episodic psychiatric condition.
The prevalence and prognostic impact of previous depression, depression in the hospital, and depression after discharge were studied in 222 patients admitted for acute myocardial infarction (MI). Patients were interviewed 1 week, 6 months, and 12 months after the index MI using a modified version of the Diagnostic Interview Schedule (DIS); patients also completed the Beck Depression Inventory (BDI). Patients or family members were recontacted at 18 months to determine survival. Some 27.5% of patients had at least one episode of major depression before their MI, but only 7.7% were depressed at some point during the year preceding the infarct. Overall, 31.5% of patients experienced depression in the hospital or during the year postdischarge. Some 35 patients were depressed in the hospital, 30 became depressed between discharge and 6 months, and five more between 6 and 12 months after the MI. History of depression increased the risk of depression in the hospital and after discharge. Depression in the hospital was associated with an increased risk of mortality over 18 months. Patients who experienced a recurrent depression in the hospital were at particularly high risk. Although patients who became depressed after discharge differed from those who remained depression-free in terms of age, history of depression, BDI scores, and the number of depression symptoms on the DIS in the hospital, a model including these variables identified only 14.7% of the patients who became depressed after returning home. Post-MI depression is common and largely unrelated to medical and psychosocial factors.
To test the hypothesis that symptoms of anxiety and depression increase the risk of experiencing hypertension, using the National Health and Nutrition Examination I Epidemiologic Follow-up Study.
A cohort of men and women without evidence of hypertension at baseline were followed up for 7 to 16 years. The association between 2 outcome measures (hypertension and treated hypertension) and baseline anxiety and depression was analyzed using Cox proportional hazards regression adjusting for hypertension risk factors (age; sex; education; cigarette smoking; body mass index; alcohol use; history of diabetes, stroke, or coronary heart disease; and baseline systolic blood pressure). Analyses were stratified by race and age (white persons aged 25-44 years and 45-64 years and black persons aged 25-64 years).
General community.
A population-based sample of 2992 initially normotensive persons.
Incident hypertension was defined as blood pressure of 160/95 mm Hg or more, or prescription of antihypertensive medications. Treated hypertension was defined as prescription of antihypertensive medications.
In the multivariate models for whites aged 45 to 64 years, high anxiety (relative risk [RR], 1.82; 95% confidence interval [CI], 1.30-2.53) and high depression (RR, 1.80; 95% CI, 1.16-2.78) remained independent predictors of incident hypertension. The risks associated with treated hypertension were also increased for high anxiety (RR, 2.36; 95% CI, 1.73-3.23) and high depression (RR, 1.89; 95% CI, 1.25-2.85). For blacks aged 25 to 64 years, high anxiety (RR, 2.74; 95% CI, 1.35-5.53) and high depression (RR, 2.99; 95% CI, 1.41-6.33) remained independent predictors of incident hypertension. The risks associated with treated hypertension were also increased for high anxiety (RR, 3.24; 95% CI, 1.59-6.61) and high depression (RR, 2.92; 95% CI, 1.37-6.22). For whites aged 25 to 44 years, intermediate anxiety (RR, 1.62; 95% CI, 1.18-2.22) and intermediate depression (RR, 1.60; 95% CI, 1.17-2.17) remained independent predictors of treated hypertension only.
Anxiety and depression are predictive of later incidence of hypertension and prescription treatment for hypertension.
Major depression is a common comorbid condition in patients with coronary heart disease (CHD). Although mild emotional distress may be a normal reaction to myocardial infarction or other manifestations of CHD, major depression should not be considered a normal reaction, nor should it be ignored. Major depression is a debilitating comorbid disorder that can seriously complicate recovery and increase the risks of further cardiac morbidity and mortality. Fortunately, it is one that can be successfully treated in the majority of cases. The purpose of this review is to present the evidence for the negative prognostic effects of depression in cardiac patients and to discuss methods for assessing and treating depression in these patients.
An exploratory study to examine the genetic and environmental influences on healthcare-seeking behavior for four health conditions (high blood pressure, mental health problems, joint disorders, and hearing problems).
Data collected from 3,602 male-male twin pair members of the Vietnam Era Twin (VET) Registry.
Varying models for the relationship between genetic and environmental influences on health condition liability and on treatment use were tested in an attempt to explain the relative contributions of additive genetic, common, and unique environmental effects to health condition and treatment use.
A mail and telephone survey of general health status was administered in 1987 to VET Registry twins.
Variance component estimates under the best-fitting model for the genetic component ranged from 24 percent to 52 percent for the condition status and from 42 percent to 56 percent for treatment-seeking behavior.
Utilization models that consider only environmental parameters will leave a large percentage of variability unexplained. Familial patterns have an impact not only on disease susceptibility but also on healthcare utilization, thereby having lifelong implications for social and fiscal constraints placed on the healthcare system. Thus, explanatory models for healthcare utilization behavior should consider the contribution of genetic factors in the decision to seek and use health services.
Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune-inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high-density lipoprotein cholesterol (HDL-C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL-C or by abnormal levels of serum total cholesterol, triglycerides, low-density lipoprotein-C (LDL-C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL-C and (iii) there are significant associations between serum HDL-C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T-helper/T-suppressor (CD4+/CD8+) T-cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL-C and total cholesterol, as well as the HDL-C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL-C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL-C or other lipid variables. Serum HDL-C levels were significantly and negatively correlated with the (CD4+/CD8+) T-cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL-C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL-C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.
Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.
Literature and folk wisdom have long linked depression and death; however, only recently have scientific studies examined the relation between them. Beginning in the 1970s, investigators compared mortality among patients treated for major depression and the general population. Nine of ten studies found an increased mortality from cardiovascular disease among depressed patients. However, such studies confound the relation between depression and its treatment. Community surveys circumvent this difficulty, but as these studies began to appear, other investigations revealed the strong association between depression and cigarette smoking, which made obvious a need to control for smoking. The first study to do this appeared in 1993, and not only did a relation between depression and mortality persist, but a relation between depression and the development of ischemic disease was revealed. In the past 2 years, six more community surveys have followed populations initially free of disease, and five have observed an increased risk of ischemic heart disease among depressed persons. Another research strategy is to start with subjects who have preexisting cardiovascular disease. Here, too, depression has consistently been associated with a worse outcome. In one well-designed study, patients with depression in the period immediately after a myocardial infarction were 3.5 times more likely to die than nondepressed patients. The basis of this association remains speculative. However, it is likely that the changes in the autonomic nervous system and platelets that are seen in depression account for a substantial portion of the association.
The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men.
Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Proband-wise concordance rates and biometric modeling were used to analyze the data.
The diagnosis of major depression (MD), as defined by DSM-III-R, and the subtype of severe/psychotic MD were significantly affected by genetic (h2=0.36 and 0.39, respectively) and nonshared environmental (e2=0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental (c2=0.27, 0.08, and 0.14, respectively) and nonshared environmental (e2=0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic (h2=0.47 and 0.10, respectively) and nonshared environmental (e2=0.53 and 0.90, respectively) factors. Early-onset MD was significantly more heritable than late-onset MD.
The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.
Increasing evidence supports an association between symptomatic depression and the risk of coronary heart disease (CHD), although no single study has compared multiple depression scales. We hypothesized that higher levels of symptomatic depression assessed from different depression scales were associated with the risk of CHD. We examined this relation in the Normative Aging Study, a prospective cohort of older men. A total of 1,305 men free of diagnosed CHD in 1986 completed the revised Minnesota Multiphasic Personality Inventory (MMPI-2). We categorized scores for the MMPI-2 D, MMPI-2 DEP, and Symptom Checklist-90 (SCL-90) depression scales. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred, including 30 cases of nonfatal myocardial infarction, 20 cases of fatal CHD, and 60 cases of angina pectoris. Compared with men reporting the lowest level of depression, men in the highest level of depression had multivariate-adjusted relative risks of incident CHD (total CHD and angina) of 1.46 (95% confidence interval 0.83 to 2.57), 2.07 (95% confidence interval 1.13 to 3.81), and 1.73 (95% confidence interval 0.97 to 3.10) for the MMPI-2 D, MMPI-2 DEP, and SCL-90 scales, respectively. Similar RRs were obtained for each CHD subtype according to each depression scale. We found strong dose-response relations between level of depression measured by the MMPI-2 DEP scale and incidence of both angina pectoris (p value for trend, 0.039) and CHD (p value for trend, 0.016). Among older men, symptomatic depression measured by any of 3 depression scales may be positively associated with the risk of CHD.
To examine the independent impact of major depression and hostility on mortality rate at 6 months and 12 months after discharge from the hospital in patients with a myocardial infarction.
Three hundred thirty-one patients were prospectively evaluated for depression with a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode. The Cook Medley Hostility Scale data were analyzed by chi(2) procedures for nominal and categoric data, and Student t test was used for continuous data types.
Depression was a significant predictor of death at 12 months (P =. 04) but not at 6 months (P =.08). Hostility was not found to be a predictor of death at 6 months or 12 months.
Major depression in patients hospitalized after myocardial infarction is a significant univariable predictor of death at 12 months, although it was not a statistically significant predictor after adjusting for other variables. Hostility is not a predictor of death. Prospective studies are needed to determine the impact of aggressive treatment of depression on post-myocardial infarction survival.
This study investigated whether symptoms of depression and anxiety were related to the development of elevated blood presure in initially normotensive adults. The study's hypothesis was addressed with an existing set of prospective data gathered from an age-, sex-, and weight-stratified sample of 508 adults. Four years of follow-up data were analyzed both with logistic analysis, which used hypertension (blood presssure ≥140 mm Hg systolic or 90 mm Hg diastolic) as the dependent variable, and with multiple regression analysis, which used change in blood pressure as the dependent variable. Five physical risk factors for hypertension (age, sex, baseline body mass index, family history of hypertension, and baseline blood pressure levels) were controlled for in the regression analyses. Use of antidepressant/antianxiety and antihypertensive medications were controlled for in the study.
Of the 433 normotensive participants who were eligible for our study, 15% had missing data in the logistic regression analysis focusing on depression (n = 371); similarly, 15% of the eligible sample had missing data in the logistic regression using anxiety as the psychological variable of interest (n = 370). Both logistic regression analyses showed no significant relationship for either depression or anxiety in the development of hypertension. The multiple regression analyses (n = 369 for the depression analysis; n = 361 for the anxiety analysis) similarly showed no relationship between either depression or anxiety in changes in blood pressure during the 4-year follow-up. Thus, our results do not support the role of depressive or anxiety symptoms in the development of hypertension in our sample of initially normotensive adults. Am J Hypertens 2001;14:660–664 © 2001 American Journal of Hypertension, Ltd.
Two possible explanations for an hypothesized association between depression and hypertension were examined: (1) shared stress-related risk factors are associated with both depression and hypertension and (2) life-style factors associated with depression lead to hypertension.
A predominantly black sample of 695 adults were interviewed in the Harlem Household Survey. Two measures of hypertension were used and compared-1) self-report and 2) elevated blood pressure (above 140/90 mm Hg)-on the basis of the mean of two blood pressure measures. Depressive symptoms were measured by use of a 24-item scale based on the Diagnostic Interview Schedule. Logistic regression models were used to test associations between hypertension and depressive symptoms, stressors, and life-style factors.
Depressive symptoms were associated with self-reported hypertension but not with elevated blood pressure. The association between self-reported hypertension and depressive symptoms was explained partly by shared stress-related risk factors but not by life-style factors. Several stressors and life-style variables were risk factors for elevated blood pressure independently of depressive symptoms. The findings are consistent with studies that have measured hypertension variously by either self-report or blood pressure. Possible explanations were explored (labeling and help-seeking) but were not supported by the data.
An association was found between self-reported hypertension and depressive symptoms, which was explained partly by shared stress-related risk factors. Elevated blood pressure was associated with stressors and life-style factors but not with depressive symptomatology. Research on illness representations and cultural dimensions of health suggest avenues for further investigation.
The aim of the study was to test the hypotheses that the trajectory of psychological risk (ie, persistent or increasing measures of depression and anxiety symptoms, anger, and low social support over time) increases the risk for the development of hypertension and that blood pressure levels fluctuate with psychological changes in women. Initially, healthy normotensive middle-aged women (n=541; 90.6% white, 8.9% African American) were followed across an average of 9.2 years of follow-up. Psychological characteristics were assessed repeatedly via standardized questionnaires, and Cox proportional hazards and random regression models were used to analyze their impact, adjusting for hypertension risk factors (age, race, years of education, parental history of hypertension, baseline blood pressure, body mass index, physical activity, alcohol use, and cigarette smoking). Seventy-five women became hypertensive during the follow-up period. Baseline levels of depression, anxiety, anger, and social support did not predict subsequent hypertension. A high level of anxiety throughout the follow-up, an increase in the level of feelings of anger, and a decrease in the level of social support over the follow-up were significant predictors of hypertension incidence (all P<0.05), although covariate adjustment reduced some of the significance levels to nonsignificance. In women, increases in depressive symptoms were significantly associated (P=0.003) with concurrent increases in the level of systolic blood pressure, especially among hypertensive patients (P=0.0001). Increasing levels of anger, decreasing levels of social support, and high anxiety increase the likelihood of women's development of hypertension in midlife. These results emphasize the importance of evaluating the trajectory of psychological risk during the period of evolving hypertension.
Clinical depression is associated with an increased risk for mortality in patients with a recent myocardial infarction (MI). Reduced heart rate variability (HRV) has been suggested as a possible explanation for this association. The purpose of this study was to determine if depression is associated with reduced HRV in patients with a recent MI.
Three hundred eighty acute MI patients with depression and 424 acute MI patients without depression were recruited. All underwent 24-hour ambulatory electrocardiographic monitoring after hospital discharge. In univariate analyses, 4 indices of HRV were significantly lower in patients with depression than in patients without depression. Variables associated with HRV were then compared between patients with and without depression, and potential confounds were identified. These variables (age, sex, diabetes, and present cigarette smoking) were entered into an analysis of covariance model, followed by depression status. In the final model, all but one HRV index (high-frequency power) remained significantly lower in patients with depression than in patients without depression.
We conclude that greater autonomic dysfunction, as reflected by decreased HRV, is a plausible mechanism linking depression to increased cardiac mortality in post-MI patients.
A populationbased twin study of major depression in women.
- Kendler