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Environmental stress and psychiatric illness
Abstract
It has long been recognized that environmental stress plays a pivotal role in the pathogenesis of psychiatric disorders. The relationship is complex and the neurobiological mechanisms that mediate the contribution of stressful experiences to the manifestation of illness are not well understood. In considering this relationship, it is important to differentiate between the role of environmental stressors as vulnerability factors that predispose the individual to psychiatric illness and may be temporally distant from its clinical onset, and their role as direct precipitants of the illness. Furthermore, environmental stressors must be considered in the context of constitutional vulnerability factors, such as genetic predisposition, with which such stressors may interact. Genetic predisposition may influence not only vulnerability to illness but also the nature of the individual's response to stress and the likelihood of exposure to stressful events. In this paper, we focus on two areas that illustrate the complexity of the field and the important findings that have emerged--the role of early parental loss (EPL) in adult psychopathology, particularly major depression, and the relationship between recent significant life events and depressive episodes. We conclude with a preliminary conceptual framework for considering the relationship between genetic susceptibility and environmental stress in the pathogenesis of psychiatric illness.
... The data were taken from a primary study that was conducted from February to November of 2016 and that involved 1026 people between the ages of 13 The units of analysis were selected by means of a systematic random sampling at care sites for this population. For this study, 540 records that reported the use of any drug in the last year were analyzed. ...
... No associations were found between the displacement variables and illicit substances. [13][14][15] CONCLUSIONS There are specific groups of substance users in populations that have been the victim of forced displacement in Colombia. Identification of these groups and their sociodemographic and displacement characteristics can be useful for specific prevention and intervention measures in the future. ...
Introduction: This study aims to further differentiate the profiles of drug users based on sociodemographic factors associated with displacement and mental health disorders, which, within the context of this research, appear to be relevant when considering substance use. Objectives: To classify a sample of the population of victims of armed displacement in Colombia into homogenous groups through an interdependent multivariate cluster analysis, taking into account substance use in the last year. Methods: The data are taken from a study involving 1026 people between the ages of 13 and 65 that was designed to investigate the mental health and drug use patterns of populations displaced by the armed conflict in Colombia in 3 cities: Bogotá, Medellín, and Buenaventura. This study selected 540 cases presenting with at least 1 instance of alcohol, tobacco, or illicit substance use in the last year. Results: Cluster analysis identified 5 alcohol, 5 tobacco, and 4 illicit substance use groups. Age, sex, occupation, and some variables related to displacement were associated with the use of these substances. Considering illicit substances, cluster 2 is the group with the most characteristics in common; as such, interventions for this group should be prioritized in public health policies aimed at this population. Conclusions: There are specific groups of substance users in populations that have been the victim of forced displacement in Colombia.
... This alarming prevalence is of particular concern given the established link between Adverse Childhood Experiences (ACEs) and subsequent psychopathology development. Conditions such as depression, anxiety, substance use, and post-traumatic stress disorder (PTSD) are significantly associated with these experiences (McLaughlin et al., 2012;Carliner et al., 2016;Alisic et al., 2014;McLaughlin et al., 2014;Kendler et al., 1995;Agid et al., 2000;Heim and Nemeroff, 2001;Ballenger et al., 2004;Heim et al., 2010;Bandelow et al., 2004;Etkin and Wagner, 2007;Yehuda et al., 2010;Kaplow and Wisdom, 2007). The clinical presentations tend to be more severe in trauma-exposed individuals, often leading to symptom development at younger ages and with increased intensity (Teicher and Samson, 2013;Nierop et al., 2015). ...
... Childhood stress, also called early life stress, broadly refers to stress experienced before reaching adulthood and includes events such as neglect, physical and psychological abuse, sexual abuse, loss of a caregiver, relationship development, bullying, accidents, illnesses, natural disasters, and wars (Heim et al. 2003(Heim et al. , 2004Agid et al. 2000). Environment is a crucial factor in providing optimal growth and health conditions for children, including social, cognitive, and immune system-related aspects (Consiglio and Brodin 2020;Ferguson et al. 2013;Mackes et al. 2020;Sonuga-Barke et al. 2017). ...
Sociality is an instinctive property of organisms that live in relation to others and is a complex characteristic of higher order brain functions. However, the evolution of the human brain to acquire higher order brain functions, such as sociality, and the neural basis for executing these functions and their control mechanisms are largely unknown. Several studies have attempted to evaluate how human sociality was acquired during the course of evolution and the mechanisms controlling sociality from a neurodevelopment viewpoint. This review discusses these findings in the context of human brain evolution and the pathophysiology of autism spectrum disorder (ASD). Comparative genomic studies of postmortem primate brains have demonstrated human-specific regulatory mechanisms underlying higher order brain functions, providing evidence for the contribution of oligodendrocytes to human brain function. Functional analyses of the causative genes of ASD in animal models have demonstrated that the neural basis of social behavior is associated with layer 6 (L6) of the neocortex and oligodendrocytes. These findings demonstrate that both neurons and oligodendrocytes contribute to the neural basis and molecular mechanisms underlying human brain evolution and social functioning. This review provides novel insights into sociability and the corresponding neural bases of brain disorders and evolution.
... In addition to frequently discussed factors such as poverty and inadequate access to healthcare, hygienic living spaces, safe neighborhood environments, and clean air (1) can promote and exacerbate psychiatric conditions such as depression, anxiety, and psychotic disorders (2). Nevertheless, even as the body of literature on mental health-gut microbiome interactions continues to expand (3,4), there is a relative dearth of research examining these interactions within the context of social inequity. ...
Social and economic inequities can have a profound impact on human health, particularly on the development and progression of chronic disease. For military veterans, exposure to unique environments and circumstances may further impact their health. There continues to be limited work regarding the influence of mental health within the context of socioeconomic inequities. In this cross-sectional study, we hypothesized that veterans residing in food deserts (e.g., places in which there is a lack of access to sufficient and/or nutritious food) would have decreased gut microbial species (α-diversity), different microbiome community compositions, and poorer quality of diet and mental health compared to non-food desert residents. The fecal microbiome of 342 military veterans was sequenced, and microbiome diversity and community composition were evaluated. Although dietary quality and α-diversity did not significantly differ by food desert status, resident status (food desert versus non-food desert) accounted for a moderate influence on β-diversity (2.4%). Factors such as race and psychiatric diagnoses accounted for greater proportions of β-diversity influence (7% and 10%, respectively). Moreover, more participants with current post-traumatic stress disorder lived in food deserts ( P < 0.04), and there were significantly more participants in the non-food desert group diagnosed with substance use disorders ( P = 0.002) and current alcohol use disorder ( P = 0.04). These findings suggest that living in a food desert, in combination with additional associated risk factors, may influence gut microbial diversity and composition. To increase ecological validity, researchers investigating the influence of inter-related biopsychosocial factors over time may benefit from adopting a life-course perspective.
IMPORTANCE
Social and economic inequities can have a profound impact on human health. The inequities could result in alterations to the gut microbiome, an important factor that may have profound abilities to alter health outcomes. Moreover, the strong correlations between social and economic inequities have been long understood. However, to date, limited research regarding the microbiome and mental health within the context of socioeconomic inequities exists. One particular inequity that may influence both mental health and the gut microbiome is living in a food desert. Persons living in food deserts may lack access to sufficient and/or nutritious food and often experience other inequities, such as increased exposure to air pollution and poor access to healthcare. Together, these factors may confer a unique risk for microbial perturbation. Indeed, external factors beyond a food desert might compound over time to have a lasting effect on an individual’s gut microbiome. Therefore, adoption of a life-course approach is expected to increase the ecological validity of research related to social inequities, the gut microbiome, and physical and mental health.
... One risk factor that is further increased by the distress during the current pandemic is the previous experience of childhood maltreatment (CM). The experience of stressful early life experiences is indicated as a relevant predictor for increased parental mental health problems and the development of psychopathologies [15,16] as well as somatic symptoms [17]. Concretely, experiences of CM are related to adverse mental health consequences, lower physical functioning, and poorer general health [18] as well as elevated prevalence rates of major depressive disorder (MDD) [19,20]. ...
Background
Social distancing strategies during the SARS-CoV-2 pandemic have left families facing a variety of different constraints. Especially in this stressful time, children need a stable parental home to prevent developmental consequences. Additional risk factors such as maternal childhood maltreatment (CM) may affect mother’s psychosomatic health and children’s physical well-being in this period.
Objective
It was aimed to analyze the associations between maternal CM, mother’s mental health, and children’s physical complaints during the SARS-CoV-2-pandemic.
Method
Mothers of a well-documented birth cohort from a longitudinal study were included in this study. Psychosomatic health was assessed with the PHQ-D and children’s physical health with the GBB-KJ during the pandemic. N = 159 mothers completed the online survey. To describe the maternal CM, data from a longitudinal survey were used.
Results
The calculation of three mediation analyses demonstrate that maternal depression symptoms (c-path: β = 0.10, p = .02; c’-path: β = 0.07, p = .13), somatic symptoms (c-path: β = 0.10, p = .02; c’-path: β = 0.07, p = .13) and psychosomatic symptoms (c-path: β = 0.10, p = .02; c’-path: β = 0.06, p = .19) fully mediate the relationship between CM and children’s physical health complaints.
Conclusions
Maternal CM experiences seem to be one relevant risk factor during the pandemic and seem to influence the way in which parents deal with stressful situations and increase the risk for depressive symptoms. The present results highlight the importance to provide individually adjusted assistance to help the families to get through the pandemic.
... Az, hogy a stressz testi és lelki megbetegedés okozója lesz-e, nagymértékben függ a stressz típusától, időtartamától és súlyosságától (Agid et al., 2000). Az enyhe, de hosszan tartó stressz fontos szerepet játszik a szomatikus és a mentális zavarok kialakulásában, és ezek kihatnak az egyén szubjektív egészségi állapotára . ...
A stressz és az agressziós szint változásai a pandémia időszaka alatt a halmozottan hátrányos helyzetű abaúji területen RUCSKA Andrea, LAKATOS Csilla Miskolci Egyetem Egészségtudományi Kar rucska.andrea@uni-miskolc.hu, lakatos.csilla@uni-miskolc.hu A pandémia elhúzódó időszaka nagy terhet rótt a társadalomra, hatása a lakosság mentális állapotában, a magatartásban, a kommunikációban manifesztálódott. A stresszre adott természetes válasz a félelem, szorongás. Amennyiben nincs a helyzet kezeléséhez szükséges megküzdési stratégiánk, kommunikációs, konfliktuskezelési készletünk, a frusztráció könnyen agresszióba fordul át. Kutatási célunk a hosszú ideig elhúzódó járványidőszakban tapasztalt bizonytalanság, félelem hatásának felmérése egy hátrányos helyzetű régió felnőtt lakossága körében a stressz és az agressziós magatartás vizsgálatával. Adatfelvételünket a járvány második, harmadik és negyedik hullámának tetőzésén bonyolítottuk le. Az online adatfelvételhez az Észlelt Stressz Kérdőív 14 tételes magyar változatát (PSS-14) és a Buss Perry agresszió kérdőívet használtuk háttérváltozók kiegészítésével. A kutatás nem reprezentatív, viszont informatív. Eredmények: az adatfelvétel során mindhárom hullámban 500 feletti kitöltést értünk el. A járvány második hullámában a válaszadók átlagéletkora 39,4±13,1 év volt, többségük (44,7%) nagyvárosban, 28,8%-uk kisvárosban, 26,1%-uk faluban élt. A harmadik hullám adatfelvételében a résztvevők átlagéletkora 34,7±13,05 év volt, a lakóhely eloszlása hasonló, mint a második hullámban. A negyedik hullámban az átlagéletkor 35,4±13,4 év volt, a lakóhelyi eloszlás minimálisan változott az előzőkhez képest. A stresszindex a negyedik hullámban volt a legmagasabb (19,84), a legalacsonyabb a harmadik hullám esetében (17,67). A férfiak stresszindexe mindhárom adatfelvételkor magasabb értéket mutatott a nőkénél. A stresszt vizsgálva a lakóhely viszonylatában nincs szignifikáns különbség (p2,3,4>0,2), a település nagysága viszont tendenciaszintű összefüggést mutat a lakók stressz-szintjével oly módon, hogy kisebb településeken élők stressz indexe alacsonyabb a nagyobb településeken élőknél. Az összesített agressziós szint a harmadik hullámban volt a legerősebb (64,3), de nem érte el a küszöbértéket. A verbális agresszió (12,5) mindhárom hullámban meghaladta a küszöbértéket. A második és a harmadik hullámban közepes erősségű, negatív korrelációt tapasztaltaltunk (r=-0,3), A negyedik hullámban gyenge korreláció mutatkozott a stressz és az agresszió között (r=0,2).
... Az, hogy a stressz testi és lelki megbetegedés okozója lesz-e, nagymértékben függ a stressz típusától, időtartamától és súlyosságától (Agid et al., 2000). Az enyhe, de hosszan tartó stressz fontos szerepet játszik a szomatikus és a mentális zavarok kialakulásában, és ezek kihatnak az egyén szubjektív egészségi állapotára . ...
... One risk factor that is further increased by the distress during the current pandemic is the previous experience of childhood maltreatment (CM). The experience of stressful early life experiences is indicated as a relevant predictor for increased parental mental health problems and the development of psychopathologies (Agid et al., 2000;Carr et al., 2013) as well as somatic symptoms (Kealy et al., 2018). Concretely, experiences of CM are related with adverse mental health consequences, lower physical functioning, and poorer general health (Herrenkohl et al., 2013) as well as elevated prevalence rates of major depressive disorder (MDD; Li et al., 2016;Widom et al., 2007). ...
Background
Preventive isolation and social distancing strategies during the SARS-CoV-2 pandemic have confronted families with a variety of different limitations and pressures like preventive isolation and school closures. Especially in this stressful time, children need a stable parental home to prevent developmental consequences. Additional risk factors such as maternal childhood maltreatment (CM) may affect mother’s psychosomatic health and children’s physical well-being in times of increased stress such as during the ongoing pandemic.
Objective
We aimed to analyze the interplay between maternal CM, mother’s mental health, and children’s physical complaints during the SARS-CoV-2-pandemic.
Method
Mothers of a well-documented birth cohort for investigating the pathways leading to resilience or vulnerability in the transgenerational transmission of CM were imbedded in an online “SARS-CoV-2 pandemic survey” assessing mother’s psychosomatic health and children’s physical health during the pandemic. 159 mothers completed the online survey. To describe the maternal CM, data from a longitudinal survey were used.
Results
Our mediation analysis demonstrates a significant positive association between the sum of maternal CM experiences, maternal psychosomatic symptoms, and their children’s physical health complaints. The maternal psychosomatic symptoms significantly mediate the interplay between CM and children’s physical health complaints, the direct effect does not remain significant when the maternal psychosomatic symptoms were included as mediator.
Conclusions
Maternal CM seems to be one relevant risk factor for mother’s psychosomatic health and children’s physical well-being during a stressful time like a pandemic. Maternal CM experiences seem to influence the way how parents deal with stressful situations and increase the risk to suffer depressive symptoms. The latter impact also their children’s physical well-being. Our results highlight the importance to carefully assess the specific situation of families with children and to provide individually adjusted assistance to help the families to get through the pandemic.
... Because of a multifactorial origin, clear gene-disease causative associations are missing in most cases. Altered epigenetic profiling has been associated with several mental health conditions (such as depression, bipolar disorder, and schizophrenia) (Akbarian and Nestler, 2013;Chase et al., 2015;Houtepen et al., 2016;Sun et al., 2013), but the influence of the sex chromosome complement and external factors (environmental, social, and cultural) is poorly understood (Alarcon, 2009;Agid et al., 2000). A comprehensive review on genetic and environmental contributions to sex differences in the vulnerability to neurological and NPDs was thus necessary to foster new research and alert on this important topic. ...
Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer’s disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson’s, autism spectrum conditions, attention-deficit hyperactivity disorders, Tourette’s syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment.
... The fact whether stress will be the trigger of a somatic or mental illness greatly depends on the type, duration and severity of stress (Agid et al., 2000). Mild but long-lasting stress has an important role in the development of somatic and mental disorders, and these influence the individual's subjective health status . ...
We have had to adopt to the situation caused by the COVID-19 pandemic in both private life and work. Besides uncertainty becoming general, our work and its environment have changed markedly in the last two years, also causing increased stress level. Our goal is to examine the changes of the employees' mental health, stress level and well-being in a disadvantaged Hungarian region during three waves of the pandemic, and the sectors where mental strain has primarily occurred. Materials and methods: Over the background variables, we used the Perceived Stress Scale (PSS-10), the WHO Well-being Index and the
... Heritability estimates range from only 40-50% for MDD [7], and genetic variation alone is not completely attributable for the risk of developing MDD. Environmental factors, such as adverse life events and psychological or physical stress, are known to be the main risk factors for MDD and are associated with inflammatory processes [6,8,9]. Epigenetic modifications of genes associated with inflammatory processes could reveal chronic pathophysiological alterations in MDD patients [10,11]. ...
The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy con-trols (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimag-ing-methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3. In the MDD group, methylation scores of cg18793688 and cg09418290 showed signifi-cant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depres-sion-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflam-matory processes in MDD.
... Risk for depression increases at adolescence (Avenevoli et al., 2015), adolescents engage in the highest documented rates of NSSI (Giletta et al., 2012), and suicide is the second leading cause of death in adolescence (Ivey-Stephenson et al., 2020). The literature identifies many protective factors, but also risk factors, including exposure to environmental stress (Agid et al., 2000). Environmental stressors (e.g., catastrophic events) have been closely linked with onset of depression (Mazurka et al., 2016), engagement in NSSI (Gratz, 2003), and suicidal ideation and behavior (Brent, 1995). ...
Objective:
Widespread concern exists about the impacts of COVID-19 and related public health safety measures (e.g., school closures) on adolescent mental health. Emerging research documents correlates and trajectories of adolescent distress, but further work is needed to identify additional vulnerability factors that explain increased psychopathology during the pandemic. The current study examined whether COVID-19-related loneliness and health anxiety (assessed in March 2020) predicted increased depressive symptoms, frequency of non-suicidal self-injury (NSSI), and suicide risk from pre-pandemic (late January/early February 2020) to June 2020.
Method:
Participants were 362 middle and high school adolescents in rural Maine (M age = 15.01 years; 63.4% female; 76.4% White). Data were collected during a time in which state-level COVID-19 restrictions were high and case counts were relatively low. Self-reports assessed psychopathology symptoms, and ecological momentary assessment (EMA) was used to capture COVID-19-related distress during the initial days of school closures.
Results:
Loneliness predicted higher depressive symptoms for all adolescents, higher NSSI frequency for adolescents with low pre-pandemic frequency (but less frequent NSSI for adolescents with high pre-pandemic frequency), and higher suicide risk for adolescents with higher pre-pandemic risk. Health anxiety predicted higher NSSI frequency for adolescents with high pre-pandemic frequency, and secondary analyses suggested that this pattern may depend on adolescents' gender identity.
Conclusions:
Results underscore the impact of COVID-19 on adolescent mental health, with benefits for some but largely negative impacts for most. Implications for caretakers, educators, and clinicians invested in adolescent mental health are discussed.
... One factor that may be of importance on how parents deal with pandemic-associated stressors seems to be the parents' own mental health. Agid et al. (2000) suggest the experience of stressful early life experiences as a relevant predictor increasing parental mental health problems. Stressful early life experiences like experiences of childhood maltreatment (CM), abuse or neglect relate to further characteristics such as adult attachment representation (Morton & Browne, 1998;Finzi et al., 2001;Baer & Martinez, 2006). ...
The social distancing measures and the related closure of education institutions have confronted young families, in particular, with various challenges. Additional risk factors such as an insecure or even unresolved maternal attachment representation may affect mental health of mothers and their children in times of increased stress such as during the ongoing pandemic. We aimed to analyze the interplay between maternal attachment representation and mother’s and children’s mental health before and during the SARS-CoV-2-pandemic. 91 mothers completed a “SARS-CoV-2 pandemic survey” examining the pandemic-related stress of their families including their own depressive symptomology and their children’s mental health. Our mediation analysis demonstrates that the mothers’ depressive symptomology significantly and fully mediated the relationship between maternal attachment representations and children’s mental health during the pandemic. In contrast, the indirect effect of the maternal attachment representation on children’s mental health before the pandemic through the depressive symptoms experienced by the mothers before the pandemic did not reach significance alongside the total and direct effect. The quality of the maternal attachment representation, promoted by childhood maltreatment, seems to be one relevant risk factor for the mothers’ and children’s mental health during a stressful time like a pandemic. The risk for mothers to develop depressive symptoms in times of a pandemic is significantly influenced by their current representation of previous attachment experiences. In addition, the mental well-being of mothers showed a considerable influence on the children’s mental health during a pandemic. The results underline the necessity to consider unique needs of family members and to offer specific support in the current crisis focusing on attachment issues.
... The pathogenic effect of stress can be interpreted in a complex, circular causal system in which biological, psychological and social factors play role as well. The fact whether stress will cause a somatic or mental illness greatly depends on the type, duration and severity of stress (Agid et al, 2000). Mild but long-lasting stress has an essential role in the development of somatic and mental disorders, and these affect the subjective health status . ...
Emergency caused by the SARS-CoV-2 has provoked several difficulties in daily life. On the other hand, it provided an opportunity to produce new attitudes toward our life and community, but also forced us to face our vulnerabilities. Outbreak of the SARS-CoV-2 highlighted that despite our vulnerability, we can manage this crisis, by being able to influence our stress reaction as well as our fears and emotions about the pandemic. Faculty of Healthcare of the University of Miskolc is training such professionals, whose priority task is to preserve the mental health of individuals and communities, reduce stress reactions, increase the available information on the subject, and help the community to adapt adequately to unexpected difficulties, like a pandemic situation. In the present study, we examined the mental state of the population of Northeastern Hungary in the second wave to adapt the above-described education to the ongoing changes caused by the pandemic. During the research, we applied an online questionnaire, that included the Hungarian version of the 10-item Perceived Stress Scale-, the Adult Hope Scale-, the WHO Well-Being, and the Buss Perry aggression questionnaire. Most participants (n=528) live in small towns or villages and their average age is 39.4±13.1. The aggression level of responders did not reach the threshold, but the level of verbal aggression exceeded it. The participants were more stressed, but they thought they could handle their problems. Consequently, the pandemic harms the mental state and health of the population, therefore the presence of health professionals is needed.
... Animal models of social stress have revealed that socially defeated rodents and monkeys display behavioral responses (i.e., social avoidance, changes in ingestive behavior and sleep, and increases in anxiety-and depressive-like behaviors) that resemble the symptoms of neuropsychiatric disorders in humans [15][16][17][18][19][20][21] . Extensive research has explored how social stress may increase the likelihood of developing a mood or anxiety disorder 15,22,23 ; however, data on the direct effect OPEN ...
Social stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.
... Adverse circumstances during this developmental period may exert neurochemical and behavioral changes that persist into adulthood (Shao et al., 2009;Vargas et al., 2016). For example, exposure to early life adversity, such as environmental stress, social instability and isolation, increases the risk to develop psychopathologies, like anxiety, depression, schizophrenia and drug addiction (Agid et al., 2000;Burke & Miczek, 2014;Lazarus & Cohen, 1977). ...
Adolescence is a developmental period characterized by neuronal growth. Environmental factors such as maternal neglect, social stress and drugs of abuse have a direct impact on future behavioral patterns. Because rats are highly social animals, we decided to investigate if isolation stress during adolescence increases conditioned place preference (CPP) to drugs of abuse. Since lower D2 receptor expression in the mesocorticolimbic system is known to increase cocaine conditioning in adult animals, and because adolescents and adults differ in dopaminergic connectivity and D2 receptor populations, we investigated if D2 receptors are altered during these conditions. Female rats were weaned at postnatal day 23 and housed singly or in pairs. At day 34 rats were tested in an open field, at day 35 in an elevated plus maze and at day 36 they were tested for CPP to cocaine (15mg/kg). At post‐natal day 48, rats were euthanized, brains collected and stored at −80°C. Single‐housed rats showed greater conditioning to cocaine when compared to group‐housed rats. This suggest that housing rats singly increases the rewarding properties of cocaine. Single‐housed rats also show lower D2 receptor immunoreactivity in the Nucleus accumbens (NAc) and the Prefrontal cortex (PFC) when compared to group‐housed rats. This correlates with the greater conditioning observed in single housed rats. Isolation stress had the effect of lowering D2 receptor populations in the NAc and PFC thus augmenting the rewarding properties of cocaine in adolescent female rats. Chronic stress during adolescence thus can lower D2 receptors and could be a determining factor in substance abuse and relapse.
Support or Funding Information
Financial assistance was provided by the Office of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE‐#1545803).
... Sie gehen mit einem erhöhten Suizidrisiko einher (Bandelow et al., 2014). (Sullivan et al., 2000;Hettema et al., 2005;Agid et al., 2000), Störungen des neuroendokrinologischen Systems nach Traumen in der Kindheit (Heim & Nemeroff, 2001) und dysfunktionale Kognitionen (Beck, 1963;Beck, 1964). ...
In dieser Arbeit wurde geprüft, ob ein leitlinienkonformes psychokardiologisches Behandlungskonzept einer herkömmlichen kardiologischen Behandlung bei psychisch belasteten kardiologischen Rehabilitanden in der Reduktion von Angst, Depression und Panik (primäre Zielkriterien) und einer Verbesserung der gesundheitsbezogenen Lebensqualität (sekundäre Zielparameter) überlegen ist. In der Nebenfragstellung wurden Unterschiede in der Wirksamkeit der Intervention in Abhängigkeit vom Geschlecht explorativ geprüft. Die Fragestellungen wurden mit einem quasiexperimentellen Studiendesign mit sequentiell aufeinanderfolgenden Kohorten untersucht. Die Zielparameter wurden zu Rehabeginn, -ende und 6 Monate nach Entlassung mit validierten Fragebögen (PHQ-9, PHQ-Panik, GAD-7 und MacNew Heart Disease-Fragebogen) erfasst. Die Hauptanalyse ergab einen kleinen signifikanten Intergruppeneffekt für den Zielparameter Depressivität zugunsten der Kontrollgruppe zu Rehaende und in der Katamnese keine signifikanten Unterschiede im Behandlungserfolg beider Studienbedingungen mehr. Die Moderatoranalyse ergab kleine Interaktionseffekte zwischen Intervention und Geschlecht für Angst und die gesundheitsbezogene Lebensqualität zu beiden Folgemess-zeitpunkten. Deskriptiv zeigte sich der Trend, dass Frauen von der Interventionsbedingung schlechter, Männer hingegen besser profitierten. Für die mangelnde Überlegenheit des Interventionsprogrammes kommen vielfältige Aspekte in Frage, die methodisch das sequentiell aufeinanderfolgenden Behandlungsdesign betreffen sowie interventionsbezogen die Ausschöpfung der Therapieressourcen, den Zeitpunkt des Behandlungsbeginns, die Behandlungsdauer, die Berücksichtigung spezifischer Patientenbedürfnisse und auch die Möglichkeit einer ungünstigen Wirkung von Psychotherapie. Ferner war die statistische Power und damit die Aussagekraft der Studie einschränkt. Als Fazit unterliegen noch vielfältige Einflussgrößen gezieltem Forschungsbedarf.
... [20][21] In considering this relationship researchers identified several vulnerability factors, such as genetic predisposition, difficult temperament, tendency to blame negative events on themselves, social, economic and environmental factors. [22][23][24] In Bangladesh, significantly higher rate of stressors both in frequency and severity was found in adolescents with self-harm, 25 somatoform disorders, 26, 27 school refusal, 28 conversion disorder, 29-31 anxiety and stress related disorders, 32 internalizing and externalizing problems, 33 juvenile idiopathic arthritis and chronic physical disorders. 34 In these studies, assessments of stressful life events were carried out using relevant section of DSM-III-R, ICD-10, Social Readjustment Rating Scale (SRRS) 35 and other foreign tools. ...
This study was aimed to produce a culturally validated scale to determine the presence of stressful life events among adolescents in Bangladesh, and formulate the relative life change units for each event. The study used qualitative research, including a focus group and questionnaire, and quantitative analysis in the validation process. Researchers first developed a provisional stress scale that was translated in Bangla through a translation exercise. Using an open-ended question along with this provisional scale on a school sample of 449 (228 rated on imagination and 221 on actual experience) adolescents, researchers developed Dhaka stress scale– adolescent with 56 items and predictive interpretation of the overall score was made. Content validity was found excellent as item level content validity index was around 1 and the scale level validity index was 0.93. The correlation coefficient was 0.72 between this scale and adolescent life events stress scale. For reliability, Cronbach’s alpha values were ranged from 0.83 to 0.97. The scale is simple to administer to assess stress in adolescents and usable in both clinical and research settings.
... El estrés psicológico tiene un rol importante en el inicio y evolución de los trastornos mentales, particularmente en la depresión (Pechtel & Pizzagalli, 2011;Hammen, 2005;Paykel, 2001). En las últimas décadas, una amplia cantidad de literatura ha evidenciado la asociación entre mayores niveles de factores estresantes, ya sean de tipo personales o ambientales, con la aparición de episodios depresivos, lo anterior tanto en estudios con muestras clínicas, como en estudios con muestras comunitarias (Agid, Kohn &, Lerer, 2000;Dean & Keshavan, 2017;Patten, Metz & Reimer, 2000). Tales factores varían de acuerdo al sexo, edad, ...
El objetivo de este estudio fue determinar la prevalencia de la sintomatología depresiva y analizar su relación con el estrés percibido y el funcionamiento familiar en una muestra de madres adultas del norte de México. Se realizó un estudio observacional analítico de corte transversal en una muestra de 118 mujeres residentes en la Zona Metropolitana de la Laguna (ZMLL), México. Para evaluar la sintomatología depresiva se utilizó el Inventario de Depresión de Beck (BDI, por sus siglas en inglés); para el estrés percibido se empleó la Escala de Estrés Percibido; y el funcionamiento familiar se evaluó mediante la Escala de Relaciones Intrafamiliares. Se utilizó el coeficiente r de Pearson para determinar el nivel de correlación entre las variables y regresión logística binomial para determinar los factores de riesgo para sintomatología depresiva en los grupos de participantes, formados de acuerdo a la edad. Los resultados indican una prevalencia del 12.7% de sintomatología depresiva clínicamente relevante, estableciendo un riesgo ocho veces mayor de presentar sintomatología depresiva para las participantes menores de 30 años que refieren niveles bajos de funcionamiento familiar (RM= 9.60, IC 95%= 1.1-84.5). Para las participantes mayores de 30 años se determinó un riesgo 15 veces mayor de presentar sintomatología depresiva, si presentan estrés percibido elevado (RM = 16.65, IC 95% = 2.7-101.3). Los factores de riesgo para presentar sintomatología depresiva varían de acuerdo a la edad de la mujer. Esto hace indispensable instrumentar medidas que amplíen la cobertura preventiva, privilegiando modelos comunitarios, sobre todo en los grupos más vulnerables.
... Le stress social est un type d'adversité important et joue un rôle essentiel dans le développement de la dépression et d'autres psychopathologies chez l'homme. (Agid et al., 2000;Björkqvist, 2001 ;Huhman, 2006 ;Slavich and Irwin 2014). De ce fait, un large nombre de modèle de dépression consiste à soumettre les animaux à des stress sociaux : ...
Le traitement de la dépression reste insatisfaisant. Avec un tiers des patients ne répondant à aucun traitement proposé, un délai d’action long, et des effets secondaires non négligeables, la nécessité de développer de nouvelles stratégies thérapeutiques devient urgente. La luminothérapie, traitement de choix de la dépression saisonnière, a été montrée depuis une trentaine d’années comme présentant également un intérêt pour le traitement des dépressions non saisonnières, unipolaires comme bipolaires. Cependant, les mécanismes d’actions sous-tendant l’effet antidépresseur de la lumière restent mal connus. L’objectif de ce travail de thèse est de comprendre, à l’aide d’un modèle original de dépression, les mécanismes neurobiologiques à l’origine de l’effet antidépresseur de la lumière. Nous avons pour cela développé un modèle de dépression combinant stress par la nage forcée et isolation sociale. Nos résultats montrent que ce protocole induit chez les animaux des comportements pseudo-dépressifs stables et résistants à des traitements classiques (escitalopram) mais également à la kétamine, utilisée récemment en étude clinique pour traiter certains patients réfractaires. Si la lumière seule à forte irradiance (Bright light stimulation, BLS, 1000 lux, une heure par jour) n’a pas d’effet antidépresseur, nous avons démontré dans notre modèle de dépression résistante que la BLS permettait de potentialiser la réponse antidépressive d’une combinaison de kétamine et de scopolamine (utilisée récemment comme d’antidépresseur potentiel) à des doses sous-efficaces. Cet effet est modulé par la sérotonine. En effet, la déplétion en tryptophane, précurseur de la sérotonine, bloque l’effet antidépresseur de cette combinaison. De manière intéressante, nous avons découvert que l’effet potentialisateur de la lumière met en jeu les astrocytes de l’habénula latérale. Ces données suggèrent que la lumière associée à la kétamine et la scopolamine, ciblerait les astrocytes afin de rétablir une activité normale dans l’habénula latérale, désinhibant les centres monoaminergiques, menant ainsi à une réponse antidépressive. Ce travail a permis de mieux comprendre les mécanismes à l’origine de la potentialisation de l’effet antidépresseur par la lumière et pourrait aider à optimiser les stratégies thérapeutiques chez les patients déprimés résistants aux traitements incluant la kétamine
... There is substanƟal evidence that the gut microbiome is a key regulator of this stress pathway 10 . Several probioƟcs 18,19 and prebioƟcs 20 have been shown to reduce corƟsol stress responses in healthy humans Early life adverse events and chronic stress are major risk factors for depression, anxiety and other psychiatric disorders 21 . HPA axis dysfuncƟon is a feature of many psychiatric illnesses, in parƟcular, mood and anxiety disorders 22 ...
The gut microbiome as a potential therapeutic target for mental illness is a hot topic in psychiatry. Trillions of bacteria reside in the human gut and have been shown to play a crucial role in gut–brain communication through an influence on neural, immune, and endocrine pathways. Patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia, and autism spectrum disorder have been shown to have significant differences in the composition of their gut microbiome. Enhancing beneficial bacteria in the gut, for example, through the use of probiotics, prebiotics, or dietary change, has the potential to improve mood and reduce anxiety in both healthy people and patient groups. Much attention is being given to this subject in the general media, and patients are becoming increasingly interested in the potential to treat mental illness with microbiome-based therapies. It is imperative that those working with people with mental illness are aware of the rationale and current evidence base for such treatment strategies. In this review, we provide an overview of the gut microbiome, what it is, and what it does in relation to gut–brain communication and psychological function. We describe the fundamental principles and basic techniques used in microbiome–gut–brain axis research in an accessible way for a clinician audience. We summarize the current evidence in relation to microbiome-based strategies for various psychiatric disorders and provide some practical advice that can be given to patients seeking to try a probiotic for mental health benefit.
... ACHD, adults with congenital heart disease. (30). ...
Congenital heart diseases (CHD) are a leading cause of morbidity in children with a high impact on the psychological health of parents. Possible short-term and long-term psychological problems among parents are addressed in the current paper. The diagnosis of CHD paired with subsequent surgical and interventional treatment and prolonged hospital stays cause acute psychological distress and can lead to posttraumatic stress disorders (PTSD). As the disease course progresses, the impact on parents’ health tends to decrease, but the risk of developing long-term psychological issues remains high. Studies have focused mainly on stress and other distressing symptoms without explicitly addressing the effects of a CHD diagnosis on the family system. Since the social environment may play an important role in parent’s life, it may be useful to conduct studies to address these issues. In particular, the psychological situation of the father and the impact of the child’s disease on the different dimensions of the father’s life, such as parenting skills and influences on the parental relationship, have been largely neglected. Recent research has also disregarded the impact of CHD on siblings of the affected child. Research on chronic diseases in general has shown that the children’s age and severity of the disease are related to an increased level of stress. Given the severity of CHD, anxiety and depression were higher in parents with children with more severe conditions. In addition, the results suggest that a positive construction of the parent-child relationship (attachment and bonding) is impaired, especially in mothers. Mothers reported worries and concerns about the challenging tasks they would face after learning about their child’s CHD and how they can deal with their child’s needs. It has also been shown that the child’s illness has a negative impact on the whole family system, including the parent’s relationship. Impairments on the parental relationship were perceived differently among mothers and fathers. Thus, there is high need for major changes to be identified,
developed and implemented in the psychological care of parents with chronically ill children. So far, research has focused more on the psychological status of parents with chronically ill children, but less research has closely examined the effects of a child’s CHD on its parent’s mental health even though there is a high demand in additional support. A holistic treatment approach should include professional parental support, especially during children’s hospitalization, information on the home care resources and services (especially respite services) and psychological support for parents.
... ACHD, adults with congenital heart disease. (30). ...
Due to technological and medical advances the population of adults with congenital heart disease (ACHD) is growing. Worldwide, congenital heart disease (CHD) affects 1.35–1.5 million children each year and more than 90% reach adulthood. Given the heterogeneity of CHD, survivors are faced with not only complex medical but also psychological challenges which may manifest in mental health problems, such as depression, anxiety and posttraumatic stress disorder. This review focuses on the emotional dimension of CHD. More precisely, it summarizes the present state of research on the prevalence of emotional distress in ACHD. Theoretical models provide a framework for possible explanations of mental health issues in ACHD. Additionally, the review examines the relation between psychological processes and overall health considering the latest scientific findings on coping with chronic illness (illness identity). There is still insufficient knowledge on the psychosocial treatment of mental health issues in the growing population of ACHD. This review suggests a vital need to further investigate the psychological situation of ACHD on a large-scale basis in order to establish a holistic treatment approach to accommodate the patients’ special needs.
... The ECS affects biologically fundamental brain functions by gating the hypothalamus-pituitary-adrenocortical axis (HPAA) stress response (Roberts et al., 2014), and striatal dopamine release by local circuit modulation of amygdala and midbrain efferents respectively (Covey et al., 2017). Differences of ECS drive in males and females might thus manifest as different sensitivies to HPAA activity, or striatal dopamine release in response to stress (Dlugos et al., 2012), a transdiagnostic psychiatric risk factor (Agid et al., 2000). This theoretical link between sex dependent psychiatric vulnerabilities and the ECS is supported by observations of the intermediary role of the ECS in estradiol effects on addiction (Peterson et al., 2016) and anxiety behaviour (Hill et al., 2007) in female rats. ...
... Social stress is argued to be the most prevalent stressor experienced by humans [1] and is thought to increase the risk or to stimulate the onset of many neuropsychiatric disorders including anxiety disorders, posttraumatic stress disorder, and depression [2][3][4][5][6]. The most commonly studied form of social stress in preclinical studies is social defeat. ...
The basolateral amygdala (BLA) is a critical nucleus mediating behavioral responses after exposure to acute social conflict. Male and female Syrian hamsters both readily establish a stable dominant-subordinate relationship among same-sex conspecifics, and the goal of the current study was to determine potential underlying genetic mechanisms in the BLA facilitating the establishment of social hierarchy. We sequenced the BLA transcriptomes of dominant, subordinate, and socially neutral males and females, and using de novo assembly techniques and gene network analyses, we compared these transcriptomes across social status within each sex. Our results revealed 499 transcripts that were differentially expressed in the BLA across both males and females and 138 distinct gene networks. Surprisingly, we found that there was virtually no overlap in the transcript changes or in gene network patterns in males and females of the same social status. These results suggest that, although males and females reliably engage in similar social behaviors to establish social dominance, the molecular mechanisms in the BLA by which these statuses are obtained and maintained are distinct.
... According to the National Centre of Child Abuse and Neglect, approximately 1.5 million verified cases of child maltreatment are reported annually in the US alone, of which more than half of the cases represent instances of neglect and about 700.000 sexual, physical, or emotional abuse (Sedlak & Broadhurst, 1996). Early parental loss (Aged, Kohn, & Lerer, 2000) and bullying (Tunnard et al., 2014) have also been reported as common adverse events during childhood that might have repercussions in adulthood. Notably, adverse experiences during childhood have been shown to be inter-dependent in the sense that the likelihood of suffering additional adversity after experiencing one increases dramatically (Dong et al., 2004). ...
This systematic review reports on moderating and mediating variables in the relationship between childhood adversity and affective disorders. Embase, MEDLINE & PsycINFO were searched from inception to October 2017, for English articles published in peer-reviewed journals investigating at least one moderating, mediating or otherwise associated variable in the relationship between childhood adversity and major depressive disorders, post-traumatic stress disorder, generalized anxiety disorder or social anxiety disorder. Overall, 214 studies were included. The review revealed that biological (i.e. heightened amygdala responses and structural neurological changes), psychological (i.e. emotional dysregulation, attachment anxiety, maladaptive cognitive style, emotion-focused coping, attentional biases, psychoform dissociation, maladaptive personality types, anxious arousal, lack of resilience, low self esteem and trauma-related guilt), and social (i.e. retraumatizations, chronic interpersonal stress, low social support and friendship) variables served as mediators between childhood adversity and affective disorders in adulthood. Furthermore, biological (i.e. genetic polymorphisms in the 5-HTT, BDNF, FKBP5, CRHR1, NR3C2, OXTR, ADCYAP1R1 genes, and alterations in the connectivity of the emotion processing circuitry), and psychological (i.e. romantic attachment avoidance and low self esteem) variables served as moderators in this relationship. A transdiagnostic moderation and mediation model is proposed, limitations are discussed and suggestions for future empirical studies are presented.
... Among environmental factors, adverse life events and stress are major risk factors for depression. 11 Converging evidence from animal and human studies suggests that psychosocial stressors trigger depression onset by inducing elevations in proinflammatory cytokine levels. 12 These psychosocial stressors are also known to influence epigenetic mechanisms, such as DNA methylation, 13 that can drive sustained changes in gene expression. ...
Importance
Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.
Objective
To identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood.
Design, Setting, and Participants
To date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts.
Main Outcomes and Measures
Whole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire.
Results
The discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%] women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 × 10⁻⁰⁸; n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 × 10⁻⁰⁹; n = 11 256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 × 10⁻⁰⁸; n = 11 256; chromosome = 15q26.1). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 × 10⁻⁰³) and of ARHGEF3 in fibroblasts (effect, −0.48; P = 9.8 × 10⁻⁰⁴) was associated with major depression.
Conclusions and Relevance
This study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects.
Strengthening families through crisis management in high-risk situations can prevent a catastrophe and save lives. This chapter defines a crisis and high-risk behaviors such as self-harm, suicidality, and harm against others that affect children's safety and disrupt the family system. It discusses the important role that medical professionals play in managing crises in children, youth, and their families. This chapter discusses some of the risk factors that increase the risk of a crisis and protective factors that mitigate and increase resiliency in children and adolescents. Communication strategies and other recommendations for supporting high-risk children and family systems are provided to help support the family system.
The hypothalamus is part of the hypothalamic-pituitary-adrenal axis which activates stress responses through release of cortisol. It is a small but heterogeneous structure comprising multiple nuclei. In vivo human neuroimaging has rarely succeeded in recording signals from individual hypothalamus nuclei. Here we use human resting-state fMRI (n = 498) with high spatial resolution to examine relationships between the functional connectivity of specific hypothalamic nuclei and a dimensional marker of prolonged stress. First, we demonstrate that we can parcellate the human hypothalamus into seven nuclei in vivo. Using the functional connectivity between these nuclei and other subcortical structures including the amygdala, we significantly predict stress scores out-of-sample. Predictions use 0.0015% of all possible brain edges, are specific to stress, and improve when using nucleus-specific compared to whole-hypothalamus connectivity. Thus, stress relates to connectivity changes in precise and functionally meaningful subcortical networks, which may be exploited in future studies using interventions in stress disorders.
Increased experience of aversive stimuli/events is a psychological‐neurobiological state of major importance in psychiatry. It occurs commonly in generalized anxiety disorder, post‐traumatic stress disorder, and major depression. A sustained period of exposure to threat (chronic stressor) is a common risk factor, and a major symptom is generalized excessive perception of, and reactivity to, aversive stimuli. In rodents, Pavlovian aversion learning and memory (PAL, PAM), quantified in terms of the conditioned defensive behavior freezing, is an extensively studied behavioral paradigm, and well understood in terms of underlying neural circuitry. In mice, chronic social stress (CSS) is a 15‐day resident‐intruder paradigm in which C57BL/6 adult males are exposed continuously and distally to dominant‐aggressive CD‐1 male mice (sustained threat) interspersed with a brief daily period of proximal attack (acute threat). To ensure that physical wounding is minimized, proximal attacks are limited to 30 to 60 s/day and lower incisor teeth of CD‐1 mice are blunted. Control (comparison) mice are maintained in littermate pairs. The CSS and CD‐1 mice are maintained in distal contact during subsequent behavioral testing. For PAL, CSS and control (CON) mice are placed in a conditioning chamber (context) and exposed to a tone [conditioned stimulus (CS)] and mild, brief foot shock [unconditioned stimulus (US)]. For PAM, mice are placed in the same context and presented with CS repetitions. The CSS mice acquire (learn) and express (memory) a higher level of freezing than CON mice, indicating that CSS leads to generalized hypersensitivity to aversion, i.e., chronic social aversion leads to increased aversion salience of foot shock. Distinctive features of the model include the following: high reproducibility; rare, mild wounding only; male specificity; absence of “susceptible” vs “resilient” subgroups; behavioral effects dependent on continued presence of CD‐1 mice; and preclinical validation of novel compounds for normalizing aversion hypersensitivity with accurate feedforward prediction of efficacy in human patients. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.
Basic Protocol 1 : Chronic social stress (CSS)
Basic Protocol 2 : Pavlovian aversion learning and memory (PALM)
Chronic stress can change how we learn and, thus, how we make decisions by promoting the formation of inflexible, potentially maladaptive, habits. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted approach in male and female mice, we reveal a dual pathway, amygdala-striatal, neuronal circuit architecture by which a recent history of chronic stress shapes learning to disrupt flexible goal-directed behavior in favor of inflexible habits. Chronic stress inhibits activity of basolateral amygdala projections to the dorsomedial striatum to impede the action-outcome learning that supports flexible, goal-directed decisions. Stress also increases activity in direct central amygdala projections to the dorsomedial striatum to promote the formation of rigid, inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to promote premature habit formation. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and other psychiatric conditions.
In recent years, it has become known that stress in childhood, called early life stress (ELS), affects the mental health of children, adolescents, and adults. Child maltreatment (CM) is an inappropriate form of childcare that interferes with children's normal brain and mind development. Previous studies have reported that CM severely affects brain development and function. For example, ELS causes brain vulnerability and increases the risk of developing psychiatric disorders. In addition, it is known that the different types and timing of abuse have different effects on the brain. Epidemiological and clinical studies are being conducted to understand the mechanism underlying abuse on a child's mental health and appropriate brain development; however, they are not fully understood. Therefore, studies using animal models, as well as humans, have been conducted to better understand the effects of CM. In this review, we discuss the effects of comparing previous findings on different types of CM in human and animal models. However, it should be noted that there are differences between animal models and humans such as genetic polymorphism and susceptibility to stress. Our review provides the latest insights into the negative effects of CM on children's development and on psychiatric disorders in adulthood.
There is now ample evidence from the preclinical and clinical fields that early life trauma has both dramatic and long-lasting effects on neurobiological systems and functions that are involved in different forms of psychopathology as well as on health in general. To date, a comprehensive review of the recent research on the effects of early and later life trauma is lacking. This book fills an obvious gap in academic and clinical literature by providing reviews which summarize and synthesize these findings. Topics considered and discussed include the possible biological and neuropsychological effects of trauma at different epochs and their effect on health. This book will be essential reading for psychiatrists, clinical psychologists, mental health professionals, social workers, pediatricians and specialists in child development.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.
Stress-related psychopathology is on the rise, and there is a pressing need for improved prevention strategies. Positive appraisal style, the tendency to appraise potentially threatening situations in a positive way, has been proposed to act as a key resilience mechanism and therefore offers a potential target for preventive approaches. In this article, we review n = 99 studies investigating associations of positive cognitive reappraisal, an important sub-facet of positive appraisal style, with outcome-based resilience and relevant other outcomes, which are considered resilience-related. According to the studies reviewed, positive cognitive reappraisal moderates the relation between stressors and negative outcomes and is positively related to several resilience-related outcomes. It also mediates between other resilience factors and resilience, suggesting it is a proximal resilience factor.
Alzheimer’s disease (AD) is a type of dementia characterized pathologically by inappropriate neuronal loss in the specific brain regions, mainly in the hippocampus and cerebral cortex, where an accumulation of insoluble plaques of amyloid-beta (Aβ) and tau tangles formation occurs, resulting in progressive memory loss, impaired thinking, deterioration and changes in personality and mood. Alzheimer’s disease now possesses a significant health burden and is considered the main source of inability among aged individuals. Recently, Alzheimer's Disease International (ADI) evaluations of 2019 featured that there would be more than 50 million individuals living with dementia around the world, a figure set to increment to 152 million by 2050. Somebody creates dementia-like clockwork, and the current year expense of dementia is assessed at US $1trillion, a figure set to twofold by 2030. AD is the leading cause of dementia and accounts for 60-80% of cases. In spite of the fact that Aβ conglomeration and neurofibrillary tangles (NFTs) development are notable major causative components engaged with AD pathogenesis, the researchers failed to cure or prevent progression of disease effectively by focusing on these pathogenic variables. Thus, tackling AD is a complex job, as we have erudite lately by continuous phase III clinical trial programs failures. Due to the lack of a clear etiology and increased morbidity associated with Alzheimer's disease, there is an immediate need to investigate the underlying causes of the disease and design and develop novel therapeutic agents to slow or reverse disease progression. Animal models mimicking different types of ADlike pathological conditions, which is an essential component in discovering potential therapeutic targets and studying mechanism of action behind that therapeutic agent, as we know, are primary tools in the field of biomedical research including AD. This chapter discusses emerging pathophysiological mechanisms and drug targets, as well as a summary of in-vivo/ex-vivo, in-vitro, QSAR, and in-silico models commonly used in Alzheimer's disease research. Moreover, we will also describe how to select suitable and valid models and the specifications and relevance of a couple of behavioral assessment methods.
An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β2-adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities. On the other hand, animals of both sexes exhibited long-term memory impairment. Our results showed that CUS decreased the expression of β2-adrenoceptors in the mPFC and D1 receptors in the mPFC and hippocampus of male rats and decreased β2-adrenoceptors and D1- receptors in the hippocampus of female. URB597 treatment had a positive effect on the short-term memory of stressed animals of both sexes whereas failed to restore long-term memory and did not affect the protein levels β2-adrenoceptors and D1 receptors in the hippocampus of CUS female rats.
The present results support that endocannabinoids induced long-term memory and neurochemical alternations which are sex dependent, suggesting sex specific treatment strategies of mental disorders.
Objective
School re-entry following hospitalization for psychiatric care has been reported as difficult for many adolescent patients. Continuous quality improvement initiatives may improve programming to enhance school re-entry experiences. The purpose of this study was to explore the school re-entry perspectives of the youth discharged from a psychiatric inpatient unit after implementing programs that patients previously identified as needed.
Methods
A survey was administered to the youth about one month after discharge to gather their perspective of their school re-entry, along with self-rated resilience and stress.
Results
Twenty-six youth (23%) participated in the post-discharge survey who reported a mean age of 15.6 years (SD 1.0), 77% identified as female, 13 (50%) provided very positive re-entry comments, eight (31%) reported moderately positive experiences, and five (19%) reported a very poor school re-entry. Mean perceived resilience (4.01, SD 0.6) and stress (3.42, SD 0.8) scores suggest youth thought they had good resilience and moderate stress.
Conclusions
Most youth reported a good school re-entry. Considerable concerns remain for the 19% who reported a poor school re-entry who may benefit from specialized outpatient or day programming post-discharge before attempting a return to school. Future directions for research are provided.
Early life adversity can disrupt development leading to emotional and cognitive disorders. This study investigated the effects of social isolation after weaning on anxiety, body weight, locomotion, and on extracellular dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) and their modulation by corticotropin releasing factor receptor 1. The day of weaning, male rats were housed singly or in groups for 10 consecutive days. Anxiety-like behaviors were assessed by an elevated plus maze (EPM) and an open field test (OF). Neurotransmitter levels were measured by in vivo microdialysis.
Single-housed rats spent less time, and entered more, into the closed arms of an EPM than group-housed rats. They also spent less time in the center of an OF, weighed more and showed greater locomotion. In the NAc, no differences in CRF, or in basal extracellular DA or GLU between groups, was observed. A depolarizing stimulus, increased DA release in both groups, but to higher levels in isolated rats, whereas GLU increased only in single-housed rats. Blocking CRF-R1 receptors with CP-154,526 decreased DA release in single-housed, but not in group-housed rats. The CRF-R1 receptor antagonist also decreased GLU in group-housed animals. These results show that isolating adolescent rats increases anxiety, body weight and ambulation, as well as the sensitivity of dopaminergic neurons to a depolarizing stimulus. This study provides further evidence of the detrimental effects of social isolation during early development and indicates that dysregulation of the CRF system in the NAc may contribute to the pathologies observed.
Introduction: Stress and depression are common among
medical students. There are number of studies on this topic,
but only few have assessed stress in clinically non-depressed
medical students.
Aim: To study the prevalence, severity and profile of stress
and depression in undergraduate medical students and to
compare the same between depressed and non-depressed
students.
Materials and Methods: A cross-sectional study was done,
on 150 undergraduate medical students of a medical college in
Northern India from February, 2018 to January, 2019. Students
Stress Dimension Questionnaire (SSDQ) was used to assess
the stress severity and to categorise various domains affected.
Hamilton Depression Rating Scale (HAM-D) was used to measure
the depressive symptoms. Chi-square, independent-t test and
one-way ANOVA were used to make the group comparisons.
Results: Mean age of the participants was 20.767 (SD=1.888).
A total of 68.67% of the participants were males. Stress and
depressive symptoms were present in 66.67% and 52% of
the participants, respectively. Of the participants having no
depressive symptoms, 50% had stress. On group comparisons,
depressed group had significantly lower mean age, higher rates
of past history of psychiatric illness, higher prevalence and
severity of stress, than non-depressed group. Prevalence of
stress and depressive symptoms decreased with increasing
seniority.
Conclusion: Medical students have high prevalence of
stress and depression. In majority of medical students having
depression, stress is present. There are still a significant
proportion of students having no depression, but having high
levels of stress. So, policy makers should take note of this while
planning interventions to address the mental health of medical
students.
Epigenetic modifications can alter gene expression through mechanisms that are heritable, but do not involve direct changes in the nucleotide sequence of the genome. Recent findings have suggested that epigenetic modifications are associated with several psychiatric disorders. As such, this chapter will introduce the general principles of epigenetics and molecular mechanisms, and discuss the implications they have on major depressive disorder. We first begin with DNA methylation, as it is the most widely studied epigenetic modification. The importance of DNA methylation is outlined by monozygotic twin studies of major depressive disorder, and the role it plays in each of the three theories of depression. Afterwards, we present two additional epigenetic modifications- histone modifications and non-coding RNAs- and their role in depression. In each section, we will also briefly touch on the therapeutic impact on patient diagnosis and care.
OBJECTIVE::
Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population.
METHODS::
A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study.
RESULTS::
Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use.
CONCLUSIONS::
Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
We examine the relationship between parental loss prior to age 17 years and adult psychopathology in 1018 pairs of female twins from a population-based registry. The relationship between loss and adult psychopathology varied as a function of the kind of loss (death vs separation), the parent involved, and the form of psychopathology. Increased risk for major depression and generalized anxiety disorder was associated with parental separation but not parental death and with separation from either mother or father. Panic disorder was associated with parental death and maternal, but not paternal, separation. Increased risk for phobia was associated with parental death and not parental separation. Risk for eating disorder was unrelated to the experience of parental loss. A model that includes parental loss as a form of "specified" family environment shows that, if it is truly an environmental risk factor for adult psychopathologic conditions, it can account for between 1.5% and 5.1% of the total variance in liability to these disorders and is responsible for between 7.0% and 20.5% of the tendency for these disorders to aggregate in siblings.
The relationship between life events and depressive disorder was assessed in 83 families ascertained through depressed probands. Contrary to expectation and to previous suggestions, we found no inverse relationship between the presence of familial loading and reactivity to stress. Thus the relatives of probands whose onset of depression followed life events or chronic difficulties had slightly higher lifetime rates of depression than the relatives of probands whose onset was not associated with adversity. There was only a weak and non-significant relationship between recent life events and current disorder among relatives, and no apparent tendency for life-event-associated depression to 'breed true' within families. Comparison with a community sample showed that the first-degree relatives of depressives had significantly elevated rates both of current depression and of recent threatening life events. This finding still held when proband-associated life events were discounted, suggesting that both liability to depression and propensity to experience life events are familial.
The incidence of traumatic events during the first ten years of life was investigated in two groups of patients suffering from major affective disorder, as well as in mixed psychiatric patients and in healthy subjects. While there were no significant differences between the two groups of affective patients or between the two control groups, the incidence of subjects who underwent such trauma was significantly higher in depressives, compared with controls. These differences are small and are further reduced if events secondary to psychiatric disturbances of family members are excluded.
Three studies are described in which measures of perceived social support from friends (PSS-Fr) and from family (PSS-Fa) were developed and validated. The PSS measures were internally consistent and appeared to measure valid constructs that were separate from each other and from network measures. PSS-Fr and PSS-Fa were both inversely related to symptoms of distress and psychopathology but the relationship was stronger for PSS-Fa. PSS-Fr was more closely related to social competence. PSS-Fa was unaffected by either positive or negative mood states (self-statements), but the reporting of PSS-Fr was lowered by negative mood states. High PSS-Fr subjects were significantly lower in trait anxiety and talked about themselves more to friends and sibs than low PSS-Fr subjects. Low PSS-Fa subjects showed marked verbal inhibition with sibs.
Parental death during childhood is widely viewed as an event so traumatic that it produces not only immediate grief and despondency but also a predisposition to react with depression when faced with loss or rejection in adult life. Empirical evidence relating to the relationship between parental death and depression is provided by more than 20 controlled studies conducted during the past 2 decades. A critical review of these studies is presented, and it is concluded that parental death during childhood has not been established as a factor of etiologic significance in adult depression or any subtype of adult depression studied to date. (29 ref)
Rat pups 2-14 days of age were exposed daily to handling (15 min of separation from mother and home cage), maternal separation (MS; 180 min of comparable separation), or were left entirely undisturbed (non-handled; NH). As adults, MS rats showed increased hypothalamic corticotropin-releasing factor (CRF) mRNA levels compared with NH rats, while CRF mRNA levels in H rats were significantly lower than either MS or NH animals. Hypothalamic CRF content under basal conditions followed exactly the same pattern. A 20-min period of restraint stress produced significant CRF depletion in all groups, although the percentage of depletion was significantly lower in H animals compared with either MS or NH animals. Restraint stress produced significantly higher increases in plasma corticosterone in MS and NH animals than in H animals. These data reflect the importance of early environmental factors in regulating the development of the hypothalamic CRF system and the responsiveness of the hypothalamic-pituitary-adrenal axis to stress.
There is increasing evidence for an important role of adverse early experience on the development of major psychiatric disorders in adulthood. Corticotropin-releasing factor (CRF), an endogenous neuropeptide, is the primary physiological regulator of the mammalian stress response. Grown nonhuman primates who were exposed as infants to adverse early rearing conditions were studied to determine if long-term alterations of CRF neuronal systems had occurred following the early stressor. In comparison to monkeys reared by mothers foraging under predictable conditions, infant monkeys raised by mothers foraging under unpredictable conditions exhibited persistently elevated cerebrospinal fluid (CSF) concentrations of CRF. Because hyperactivity of CRF-releasing neurons has been implicated in the pathophysiology of certain human affective and anxiety disorders, the present finding provides a potential neurobiological mechanism by which early-life stressors may contribute to adult psychopathology.
To determine whether there is a pattern of social characteristics that specifically predicts persistent major depression at 36 weeks follow-up.
Sixty-eight consecutive cases with a first-episode DSM-III-R diagnosis of major depression completed a life events and friendship difficulties interview at presentation and again at 36 weeks.
Four factors were associated with persistent psychiatric disorder in general: lack of a maternal confiding relationship with current partner, family dysfunction and poor friendships at presentation, and severely disappointing events between presentation and follow-up. There was no association between these adverse experiences. No combination of long-term or recent life events or difficulties was, however, specifically associated with persistent depression.
Nonsocial factors may need to be taken into account to specifically explain the phenotypic persistence of major depressive disorder in first-episode nonrecovered cases within a year of presentation. Psychosocial interventions with first-degree relatives and current close friendships should be considered as a part of the treatment strategy for first-episode major depression.
Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression.
The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent's behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis.
While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs.
Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.
Early research suggested that the loss of a parent during childhood can lead to depression and other psychopathology in children and adults. More recent research has differentiated between loss due to death and separation from parents and has questioned the link between early parental death and psychopathology. We examined the hypothesis that separation from parents has a more detrimental effect than the death of a parent on the mental health of adolescents in the community. Israeli adolescents (N = 844) with a mean age of 16.7 +/- 1.0 years (mean +/- SD) participated in this study. Seventy reported that a parent did not live at home during one of three 5-year periods until they reached the age of 15; 37 reported the death of a parent and 777 were from intact families. All participants completed the Brief Symptom Inventory (BSI), General Well Being Schedule (GWB), Parental Bonding Instrument (PBI), and Perceived Social Support Family/ Friends Scales (PSS-Fam and PSS-Fr). Adolescents who had experienced separation from parents had more psychiatric symptoms (BSI), expressed a lower sense of well-being (GWB), experienced less support from their family (PSS-Fam), and felt less cared for and more controlled by their parents (PBI) compared with those belonging to intact families. The death of a parent was not associated with significantly different scores on these variables. When we controlled for parental bonding (PBI) and perceived social support from family (PSS-Fam), the differences between the separation group and the intact family group were no longer significant. The psychological impact of separation from parents involves a greater risk for psychopathology than the death of a parent. The quality of the relationship with the parents moderates the negative impact of separation from them.
Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed.
This study examines the relationship between various possible precipitating events and the onset of unipolar depressive illness in 100 patients. The precipitating factors studied were: (1) deprivation prior to age 16 as a result of loss of parents by death, separation or divorce; (2) personal losses through death in the year before admission; (3) threatened personal losses; and (4) physical illness in the preceding six months. Patients whose depressive illness started before age 40 had a significantly higher incidence of real or threatened personal losses than did later-onset depressives (after 40). Twelve patients claimed a personal loss preceding the onset of depressive symptoms. Using 51 well relatives of the patients, matched for age and sex as controls, two claimed a similar type of personal loss. The difference between the two incidences, patient 12% and control of 3.9%, is not statistically significant.
Life events experienced in the six months before a suicide attempt were compared with events for two matched control groups. Suicide attempters reported four times as many events as were reported by subjects from the general population and 11/2 times as many as were reported by depressed patients prior to depressive onset. A substantial peaking of events occurred in the month before the attempt.
The excess over general population controls spanned most types of event. That over depressive onset was more selective, and it involved events with threatening implications, including undesirable events, those rated as stressful, and those outside the respondent's control. Unlike depression, suicide attempts were preceded equally by entrances and exits in the social field. Overall, the findings indicate a strong and immediate relationship between suicide attempts and life events.
• We examine the relationship between parental loss prior to age 17 years and adult psychopathology in 1018 pairs of female twins from a population-based registry. The relationship between loss and adult psychopathology varied as a function of the kind of loss (death vs separation), the parent involved, and the form of psychopathology. Increased risk for major depression and generalized anxiety disorder was associated with parental separation but not parental death and with separation from either mother or father. Panic disorder was associated with parental death and maternal, but not paternal, separation. Increased risk for phobia was associated with parental death and not parental separation. Risk for eating disorder was unrelated to the experience of parental loss. A model that includes parental loss as a form of "specified" family environment shows that, if it is truly an environmental risk factor for adult psychopatholgic conditions, it can account for between 1.5% and 5.1% of the total variance in liability to these disorders and is responsible for between 7.0% and 20.5% of the tendency for these disorders to aggregate in siblings.
This work was originally started because attention had been drawn to the high suicide rate in Hampstead. Geffen and Warren (1) originally reported this high rate. During the last ten years it has varied between 20 and 30 per 100,000 inhabitants (see Table I). It also compares with the suicide death rate of 10 per 100,000 for the whole community.
Advances in the human genetic map, and in genetic analysis of linkage and association in complex inheritance traits, have led to genetic progress in the major psychoses. For chromosome 6 in schizophrenia, and chromosomes 18 and 21 in manic-depressive illness, there are reports of linkage in several independent data sets. These are small effect genes, best detected with affected-relative-pair linkage methods. Association with candidate genes is an alternative strategy to uncovering susceptibility genes for these illnesses, but convincing associations remain to be demonstrated. New clinical and laboratory investigation methods are being developed. Testing every gene in the human genome for association with illness has recently been proposed (Risch and Merikangas 1996). This would require further progress in characterizing the genome and in automated large-scale genotyping. The best type of pedigree sampling for common disease studies, whether for linkage or association, is not yet established. An endophenotype hybrid strategy can combine genetic linkage, association, and pathophysiologic studies. As clinical molecular investigation methods advance, identification of disease susceptibility mutations and delineation of their pathophysiological roles may be expected.
A matched controlled study of 84 depressed women confirms the findings of Browm et al, that loss of mother before 11, three or more children at home under 14 years of age, lack of a confiding marital relationship and lack of employment may be vulnerability factors predisposing to depression in working-class women.
Synopsis
Occurrence of life events was recorded in 30 recovered depressed women undergoing clinical relapse in a controlled trial of maintenance treatment with amitriptyline and psychotherapy, and in 30 matched patients who did not relapse. Overall, patients who relapsed experienced significantly more life events in the three months before relapse, and especially in the month immediately preceding it. Undesirable events were particularly implicated. Event rates prior to relapse were closely comparable in treatment subgroups, giving no evidence that differential stress was required to produce relapse. The findings reinforce previous studies indicating an overall relationship between life events of certain types and depression, but do not suggest that the beneficial effects of maintenance treatment are specifically protective against life stress.
Recent losses occurring in the two years before onset of depression in women are distinguished from past losses occurring at any time before this. Of past losses only loss of mother before II is associated with greater risk of depression--both among women treated by psychiatrists and among women found to be suffering from depression in a random sample of 458 women living in London. Past loss of a father or sibling before 17 (or a mother between II and 17), or a child or husband, is not associated with a greater chance of developing depression. However, among patients all types of past loss by death are associated with psychotic-like depressive symptoms (and their severity) and other types of past loss with neurotic-type depressive symptoms (and their severity). It is argued that these associations probably reflect direct causal links, and a sociopsychological theory to explain them is discussed.
Life events experienced in the six months before a suicide attempt were compared with events for two matched control groups. Suicide attempters reported four times as many events as were reported by subjects from the general population and 11/2 times as many as were reported by depressed patients prior to depressive onset. A substantial peaking of events occurred in the month before the attempt. The excess over general population controls spanned most types of event. That over depressive onset was more selective, and it involved events with threatening implications, including undesirable events, those rated as stressful, and those outside the respondent's control. Unlike depression, suicide attempts were preceded equally by entrances and exits in the social field. Overall, the findings indicate a strong and immediate relationship between suicide attempts and life events.
The idea of a triggering effect in schizophrenia emphasises the role of life events as precipitating factors which act on an individual's specific predisposition towards the illness (Wing, 1978).
We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.
We studied the relationship between 2 types of psychosocial factors, life events and chronic stress, and the numerical order of the depressive episodes. The population studied consisted of 97 subjects suffering from major depressive disorder and 65 controls. Life events occurred with the first 2 depressive episodes with significantly higher frequency than with later episodes or with the control group. Patients in the third or later episode had no more life events than controls. No significant differences were apparent in the incidence of chronic stress in the different depressive episodes of the patient group or in the comparison of this group with controls. No second order interaction between life events and chronic stress was found.
Sixty middle-aged urban women with a major depressive episode (DSM-III) diagnosed in a community survey were compared with those 400 participants of the study who had no history of major depression. There were no significant differences between groups regarding most childhood demographic variables such as grade of urbanization, social class, school education, size of sibship and ordinal position. The subjects with major depression and especially those with melancholia had experienced parental loss before age 17 significantly more often than had the controls. This difference dealt only with parental divorce and other separations but not with parental death. There were no significant differences regarding parental death between melancholics, non-melancholic major depressives and controls.
In a comparison with 300 matched controls, significantly more of 300 patients with nonendogenous depression had experienced permanent separation (not due to death) from their mother before both 11 and 17 years of age and significantly more had experienced permanent separation from their father (not due to death) before both 11 and 17 years of age. The results suggest that early permanent separation from mother is a risk factor for nonendogenous depression but occurs in only about 6.7% of these patients before 11 years of age and in about 10% before 17 years of age and early permanent separation from father is also a risk factor for nonendogenous depression and occurs in about 9.3% of these patients before 11 years of age and in about 16.7% before 17 years of age.
The occurrence of life-change events (as defined by the social readjustment rating questionnaire) prior to disease onset was measured in a group of 74 patients suffering from primary depressive disorders. The resultant frequency distribution histogram was unimodal. Patients with a positive family history for depression did not differ significantly, in these measurements, from those with a negative family history nor did patients with "endogenous" depression differ significantly from those with "reactive" depression. We were, therefore, unable to distinguish two populations within the depressed group using this parameter. We conclude that the terms "endogenous" and "reactive" are misleading for the majority of patients with depressive illness.
The results of an investigation into parental bereavement during childhood in a series of 279 psychiatric patients from the Leeds area is presented. The series consists of 162 depressive patients (103 in-patients and 59 out-patients), 69 schizophrenic patients and 48 individuals suffering from anxiety state. Control data have been obtained from a group of 100 psychiatrically normal Leeds general hospital out-patients and from two sets of control material originally employed by Felix Brown (1961).
The findings are as follows:
1. In-patient, but not out-patient, depressives show an excess of maternal bereavement before the 15th birthday which is just significant at the p < 0.05 level.
2. Schizophrenics show no excess of childhood parental mortality.
3. Patients with anxiety state show no excess of childhood parental mortality.
4. There is no excess of paternal mortality for any diagnostic category.
5. None of the diagnostic categories shows any significant excess of parental bereavement occurring at a particular stage in childhood.
The significance of these findings is discussed.
The accidental event of childhood bereavement by death of a parent, and its possible importance in the later development of psychiatric illness, has been under study in recent years. It is a truism to state that, in the present organization of European society, such an event is a catastrophe, but whether bereavement is an event of aetiological importance in mental illness has not yet been decided.
Introductory View
Bereavement is only the most measurable of many possible traumata in childhood; it is fortunately not the commonest and its frequency is still diminishing.
Synopsis
In a matched controlled clinical study of 300 neurotic depressives collected over 6 years, 13% had experienced parental death before 17 years of age compared with 10·7% of the controls; this difference was not significant. There were no significant differences between the two groups when maternal or paternal death was examined separately either before 11 or 17 years of age. Thus the experience of parental death as a child is not in itself a risk factor for neurotic depression as seen in psychiatric patients.
In a matched controlled study of 71 depressed men, parental loss before 17 years, poor marriage, and unemployment were found to be vulnerability factors associated with depression in men.
I reviewed studies examining the hypothesis that life events that occur during childhood or early adolescence may predispose a person to a depression in adulthood. Of studies that compared the incidence of childhood bereavement or other childhood loss events among depressed patients and controls, the majority found an increased incidence among the depressives. Although discrepant negative findings exist, it seems that the childhood loss of a parent by death generally increases depressive risk by a factor of about 2 or 3. In addition, early loss events also seem to be related to the severity of subsequent depression and to attempted suicide. Despite this significant association between childhood loss events and depression, most depressives have not experienced an early loss event, and clearly other causal factors are operative as well.
The aim of this study is to determine in a Japanese sample whether or not the permanent loss of a parent by death or separation in childhood is aetiologically associated with unipolar major depressive disorder (according to RDC). We compared the incidence of parental loss before 17 years of age by death or separation between 122 depressed inpatients and 94 non- and never-depressed medical controls. Early maternal death was found to be significantly more common in the depressives than in the controls. Separation from either parent also showed a trend towards an increased incidence in the depressive group. No significant difference in the incidence of early paternal death was found.
To examine the relationship between stressful life events and major depressive disorder (MDD) in adolescents.
Adolescents (aged 12 to 18 years) with a current episode of MDD based on Research Diagnostic Criteria (n = 39) and normal controls free of any Axis I lifetime psychiatric disorder (n = 35) were assessed using the Life Events Record.
MDD and normal control adolescents had similar rates of total stressful life events in the year before being interviewed. Stressful life events were dichotomized into those that were most likely either independent of or dependent on the adolescent's influence/behavior. Depressed adolescents had significantly more dependent stressful life events during the previous year than did the normal controls. Further analyses showed that depressed adolescents with dependent stressful life events scored lower on symptom clusters and accordingly were less severely depressed than depressed adolescents without dependent life events.
The results of this study indicate that depressed adolescents have an increased risk for experiencing dependent life events. Furthermore, these data suggest that dependent life events in depressed adolescents are differentially associated with the type and severity of symptom presentation. The temporal occurrence, severity, and type of stressful life events as they relate to the onset, phenotypic expression, and maintenance of depression in adolescents need to be more fully understood.
Research on the relationship between stress and schizophrenia is fraught with conceptual and methodological problems. These problems include issues related to the nature and measurement of stress, the likelihood of reciprocal influences between stress and symptoms, and the adequate assessment of symptoms. Several recommendations are made regarding future research in this area. These include using multiple and broadly based measures of different types of stressors and symptoms, greater use of truly prospective research designs, and the evaluation of the effects of interventions specifically designed to reduce stress in patients who suffer from schizophrenia.
Empirical research concerning the relationship between life event stressors and schizophrenia is critically reviewed. In accordance with the view that patients suffering from schizophrenia are vulnerable to stress, there is evidence of a relationship between stressors and variation in severity of symptoms over time. There is less indication that schizophrenic patients have had higher levels of stressors than the general population or than patients suffering from other psychiatric disorders. These findings are consistent with vulnerability-stress models of the development of schizophrenia.
The aim of this study was to examine the influence of different types of disruptions in childhood parental care before the age of 15 years as risk factors for major depression in women aged 18 to 44 years. The types of disruptions studied were parental death, parental separation or divorce, other types of loss (i.e. adoption, foster-care, etc.), and prolonged separation from both parents. Potential confounding factors were also examined.
The data were obtained from a community probability sample. Caseness was determined by the use of the Diagnostic Interview Schedule (DIS) and both the current (one month) and lifetime prevalence periods were considered. Logistic regression was used to model the influence of each factor, singly and adjusted for the influence of other factors, on the risk for major depression.
It was found that in this population 17% had experienced some type of parental loss (parental death 4%, separations/divorce 10% and other types of loss 3%) and 11% had experienced prolonged separation from both parents. Parental loss was significantly associated with lifetime depression, but this effect was no longer significant when adjusted for other factors. However, prolonged separation from both parents was associated with an increased risk of current and lifetime depressive episodes of approximately three to fourfold, even when the risk was adjusted for other factors.
The results of this study suggest that prolonged separation from both parents has a stronger association with current or lifetime depression in women than do parental death, separation/divorce and other types of loss. Prolonged separation may be a marker for other risk factors and may not be a risk factor on its own.
1. Both major depression and dysthymia (chronic, low grade depression) were associated with increased reports of minor stressors (daily hassles), and feelings of loneliness, reduced uplifts, as well as the use of inappropriate coping strategies (i.e., emotion-focussed rather than problem-oriented coping). 2. Although major depressive and dysthymic patients shared several features with respect to symptomatology, dysthymics tended to report a greater number of hassles than major depressives. 3. Treatment with serotonin reuptake inhibitors over an 8-week period resulted in a marked alleviation of the depressive symptoms in both patient groups, although the clinical effectiveness of the drugs appeared somewhat later in dysthymics. 4. The attenuation of the depressive symptoms was accompanied by a modest, but significant diminution in reports of minor stressors, while the perception of uplifts remained unchanged. Moreover, recovery from depression was associated with changes in coping style, such that patients relied less on inappropriate emotion-focussed coping strategies.
This prospective study investigated whether major depressive disorder can cause negative life events. One hundred and thirteen normal college men have been followed biennially from age 26 until age 62. Fourteen major negative life events were assessed retrospectively by a self-report checklist. A blind rater read each man's complete records over the 35 years and used the same checklist prospectively. The negative life events were divided into dependent and independent groups according to whether the men's own behavior could have played a role in causing the events. In comparison with the normal control group, depressed individuals had a higher density of dependent negative life events after their first episode of depression. This difference did not exist for the occurrence of independent negative life events. Independent negative life events tended to be related to help seeking behaviors rather than to depression. This study confirmed our hypothesis that affective spectrum disorder can generate self-induced negative life events, which may contribute to the chronicity of the disorder.
In addition to a genetic contribution to the vulnerability for mood and anxiety disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), a preeminent role of early adverse life events in the pathogenesis of these disorders has been postulated. Corticotropin releasing factor (CRF), which has been conclusively documented to be the major regulator of the mammalian stress response, may be the seminal neurobiological substrate mediating the effects of early life stress on subsequent psychopathology. Central administration of CRF produces many of the physiological and behavioral effects of stress and of anxiety and depression. Clinical studies have provided evidence for increased activation of CRF neuronal systems in both MDD and PTSD. Similar hyperactivity of CRF neurons and sensitization of the pituitary-adrenal stress response has been observed in adult animals exposed to stress early in life. We propose that early adverse life events might render the human individual vulnerable to the effects of stress later in life, resulting in an increased risk for developing psychopathology via long-lived alterations in CRF-containing neural circuits. Based on these findings, new therapies including early intervention can now be developed to treat individuals exposed to severe stress early in life.
To examine the significance of acute life events and ongoing difficulties in adolescents with a recent major depressive disorder.
Adolescents (aged 13-18 years) with a recent episode of major depressive disorder based on DSM-III-R (n = 26) and normal controls free of any Axis I lifetime psychiatric disorder (n = 15) were assessed using the investigator-based Life Events and Difficulties Schedule (LEDS).
Traditionally defined severe events were more likely to occur in the year prior to onset among depressed adolescents (46%) than in a comparable period among normal controls (20%), but these differences did not reach statistical significance. Expanding the definition of severe events to include those events focused on others important to the adolescent resulted in a significantly higher percentage of depressed adolescents having one or more refined "severe" events in the year prior to onset (62%) compared with normal controls (27%) (p < or = .02). It is interesting that one half of the depressed adolescents had two or more refined severe events occur during the year prior to onset compared with none of the normal controls (p < or = .01). Further analyses showed that depressed adolescents were significantly more likely to have a major difficulty precede the onset of their depression (27%) compared with normal controls (0%) (p < or = .04).
The results suggest that depressed adolescents are exposed to high levels of stress prior to becoming depressed. Future investigations might benefit from using the LEDS with adolescents to assess acute and ongoing stressors.
The current focus on identifying genes which predispose to psychiatric illness sharpens the need to identify environmental factors which interact with genetic predisposition and thus contribute to the multifactorial causation of these disorders. One such factor may be early parental loss (EPL). The putative relationship between early environmental stressors such as parental loss and psychopathology in adult life has intrigued psychiatrists for most of this century. We report a case control study in which rates of EPL, due to parental death or permanent separation before the age of 17 years were evaluated in patients with major depression (MD), bipolar disorder (BPD) and schizophrenia (SCZ), compared to individually matched, healthy control subjects (MD-Control, 79 pairs; BPD-Control, 79 pairs; SCZ-Control, 76 pairs). Loss of parent during childhood significantly increased the likelihood of developing MD during adult life (OR=3.8, P=0.001). The effect of loss due to permanent separation (P=0.008) was more striking than loss due to death, as was loss before the age of 9 years (OR=11.0, P=0.003) compared to later childhood and adolescence. The overall rate of EPL was also increased in BPD (OR=2.6, P=0.048) but there were no significant findings in any of the subcategories of loss. A significantly increased rate of EPL was observed in schizophrenia patients (OR=3.8, P=0.01), particularly before the age of 9 years (OR=4.3, P=0.01). Comparison of psychosocial, medical and clinical characteristics of subjects with and without a history of EPL, within the larger patient groups from which the matched samples were drawn (MD, n=136; BPD, n=107; SCZ, n=160), yielded few significant findings. Among the controls (n=170), however, subjects who had experienced EPL, reported lower incomes, had been divorced more frequently, were more likely to be living alone, were more likely to smoke or have smoked cigarettes and reported more physical illness (P=0.03-0.001). Long term neurobiological consequences of early environmental stressors such as maternal deprivation have been extensively studied in many animal species. Recently, enduring changes in hypothalamic-pituitary-adrenal axis function, including corticotrophin releasing factor gene expression, have received particular attention. Analogous processes may be implicated in the effect of EPL on human vulnerability to psychopathology, via alterations in responsiveness to stress. Genetic predisposition may influence the degree of susceptibility of the individual to the effects of early environmental stress and may also determine the psychopathological entity to which the individual is rendered vulnerable as a consequence of the stress.
Data from a community-based longitudinal study were used to investigate whether childhood abuse and neglect increases risk for personality disorders (PDs) during early adulthood.
Psychosocial and psychiatric interviews were administered to a representative community sample of 639 youths and their mothers from 2 counties in the state of New York in 1975, 1983, 1985 to 1986, and 1991 to 1993. Evidence of childhood physical abuse, sexual abuse, and neglect was obtained from New York State records and from offspring self-reports in 1991 to 1993 when they were young adults. Offspring PDs were assessed in 1991 to 1993.
Persons with documented childhood abuse or neglect were more than 4 times as likely as those who were not abused or neglected to be diagnosed with PDs during early adulthood after age, parental education, and parental psychiatric disorders were controlled statistically. Childhood physical abuse, sexual abuse, and neglect were each associated with elevated PD symptom levels during early adulthood after other types of childhood maltreatment were controlled statistically. Of the 12 categories of DSM-IV PD symptoms, 10 were associated with childhood abuse or neglect. Different types of childhood maltreatment were associated with symptoms of specific PDs during early adulthood.
Persons in the community who have experienced childhood abuse or neglect are considerably more likely than those who were not abused or neglected to have PDs and elevated PD symptom levels during early adulthood. Childhood abuse and neglect may contribute to the onset of some PDs.
In spite of substantial advances in the treatment of major depression by pharmacotherapy and other means, a significant number of depressed patients require hospitalization. In the context of the Jerusalem Collaborative Depression Project, possible precipitants of psychiatric hospitalization were sought in a cohort of patients (n = 107) who were admitted to hospitals in the Jerusalem area during a 14-month period because of a depressive episode. The patients fulfilled DSM III-R criteria for major depression, single or recurrent; bipolar 1 disorder, depressed or mixed; bipolar 2, depressed. The cohort encompassed more than two thirds of potential subjects admitted during this period with the ICD-9 equivalents of the specified diagnoses (as reported to the Israel Ministry of Health National Psychiatric Case Register) and were similar to the entire potential population in terms of their diagnostic breakdown. The patients underwent extensive socio-demographic and clinical evaluation that included detailed documentation of treatment received prior to hospitalization. Notwithstanding the absence of a comparison group of depressed patients who were not hospitalized, a number of potential precipitants were identified. These included older age (55.2% > 60 years, 20.6% > 70 years), immigration to Israel during the preceding 5 years (34.7%), concomitant physical illness (60%) which was associated with moderate to severe disability in 41% and poor quality of antidepressant pharmacotherapy prior to hospitalisation (only 24.3% received an adequate trial of antidepressant medication). Further evaluation of these and other potential factors could facilitate targeting of patient groups at particular risk for hospitalization and reduce the need for it.
Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed.