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Adjusted mean inflammatory levels across medication groups and sex based on analyses of covariance (ANCOVA) adjusted for age, education, smoking status, alcohol intake, body mass index (BMI), physical activity, cardiovascular disease, diabetes, number of other chronic diseases, statins and anti-inflammatory medication; to normalize distributions C-reactive protein (CRP), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) were ln-transformed, for interpretation purposes presented means were back transformed. Abbreviations: IDS, inventory of depressive symptoms score; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; TeCA, tetracyclic antidepressant. 1Current depressive disorder and IDS 25 without medication use (=reference); only significant differences from reference are shown: *P<0.10; **P<0.05.
Source publication
Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but the exact nature of this association is still unknown and may be restricted to specific subgroups. This study examines the association between depressive disorders, depression characteristics and antidepressant medication with inflammation in a large co...
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Purpose:
In this prospective study, we examined whether early reduction in depressive symptoms predicts later remission to duloxetine in the treatment of depression, as monitored using the Montgomery-Asberg Depression Rating Scale (MADRS).
Patients and methods:
Among the 106 patients who were enrolled in this study, 67 were included in the stati...
Citations
... In studies, major depressive disorder has been associated with elevated levels of proinflammatory cytokines. [16] It is well known that high CRP levels are a predictor of CVD and that people with depression are more likely to develop it than those without depression. The association between depression and elevated CRP levels may also contribute to the association between depression and a higher risk of CVD and mortality. ...
A BSTRACT
Background
Depression has been shown to be correlated with cardiovascular (CV) morbidity and mortality. Inflammation and autonomic nervous system (ANS) dysfunction are possible causes. Numerous clinical studies have found an association between inflammatory pathways and the ANS. The aim of this study was to investigate the relationship between different heart rate variability (HRV) parameters and C-reactive protein (CRP) levels in depressed patients without concomitant diseases.
Materials and Methods
Sixty-five depressed patients who were not taking medication participated in this cross-sectional study. The Tenth Revision of the International Classification of Diseases and Related Health Problems (ICD-10) categorization of mental and behavioral disorders served as the basis for the diagnosis of depression. HRV processing and analysis were performed using ADInstrument’s Pro LabChart (PowerLab 8Pro) data analysis software. HRV was recorded for 5 min in an upright sitting position using a lead II electrocardiogram (ECG) (short-term HRV). CRP levels were measured using an ELISA (enzyme-linked immunosorbent assay) test.
Results
None of the measures of HRV showed a significant relationship with pulse rate, systolic blood pressure, diastolic blood pressure, or body mass index (BMI). Weight and BMI were strongly positively related ( r = 0.420, P = 0.003) to pRR50 (percentage of successive RR intervals differing by more than 50 ms). Very low frequency (VLF), low frequency (LF), and the LF/HF (high frequency) ratio were all strongly positively correlated with CRP ( r = 0.595, P = 0.001), whereas HF was also significantly negatively correlated ( r = 0.383, P = 0.007). CRP had a significant negative correlation with the logarithm (ln) HF and a significant positive correlation with lnVLF, lnLF, and lnLF/HF.
Conclusion
Measurement of resting HRV and CRP may be helpful in detecting CV disease in depressed patients. Low HRV and elevated serum CRP should prompt physicians to begin treatment for risk CV as soon as possible.
... The length of the antidepressant effects is being investigated in follow-up research. SAINT's effectiveness in other conditions, such as obsessive-compulsive disorder, addiction, and autism spectrum disorders, will be investigated by the researchers [38] . ...
... These seemingly contradictory findings might be attributed to brain, gene expression, and behavioral characteristics, coping styles, life experiences, cultural expectations, and inherent biological differences throughout one's lifespan [1,9,11,32]. Another possible explanation is that male individuals may present significantly higher levels of immune-inflammatory markers (e.g., CD3, CD4, and CD8) [45], while female individuals may demonstrate relatively greater risk for inflammation-related depression [46]. Future longitudinal studies examining sex differences in unipolar and bipolar depression, immune-inflammatory markers and lipoprotein profiles, and anhedonia are needed to validate these findings. ...
Background
Anhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging evidence suggests that sex differences in immune-inflammatory markers and lipoprotein profiles are associated with anhedonia.
Methods
The demographic and clinical data, immune-inflammatory markers (CD3, CD4, and CD8), and lipoprotein profiles [TC, TG, LDL-C, HDL-C, lipoprotein(a) Lp (a)] of 227 patients with unipolar and bipolar depression were collected. The Hamilton Depression Rating Scale (HAMD) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess depression and anhedonia symptoms. Data were analyzed using ANOVA, logistic regression, and receiver operating characteristic curves.
Results
Male patients in the anhedonia group had higher levels of CD3, CD4, and CD8, and lower levels of Lp (a) than the non-anhedonia group, while no significant difference was identified in female patients with and without anhedonia. Logistic regression analysis showed that CD3, CD4, CD8, and Lp (a) levels were associated with anhedonia in male patients. Furthermore, the combination of CD3, CD4, CD8, and Lp (a) had the strongest predictive value for distinguishing anhedonia in male patients than individual parameters.
Conclusions
We identified sex-specific associations between immune-inflammatory markers, lipoprotein profiles, and anhedonia in patients with unipolar and bipolar depression. The combination of CD3, CD4, CD8, and Lp (a) might be a possible biomarker for identifying anhedonia in male patients with unipolar and bipolar depression.
... Lowgrade, increased CRP levels may indicate depression, After controlling for socio-demographic, lifestyle, and disease covariates, studies found no association between depression and elevated serum CRP, and two studies found a negative association. However, other studies reported no significant differences between controls and patients with BD [23,28]. ...
Background
Differentiating unipolar depression from bipolar depression is clinically important. The identification of biomarkers that characterize the pathophysiology of each disorder may provide biological targets for treatment. The objective of the study was to demonstrate a relationship between CRP level and the severity of depressive symptoms and see if C-reactive protein (CRP) levels can be used as a biomarker to distinguish between unipolar and bipolar depression. A convenience sample of 90 individuals was consecutively recruited from the psychiatry outpatient clinic at Beni-Suef University Hospital, Egypt. They were divided into three equal groups: patients with major depressive disorder (MDD) (group 1), bipolar depression (group 2), and a healthy volunteer group (group 3). Patient groups were assessed using semi-structured interviews, and CRP levels were measured.
Results
Patients with bipolar depression and MDD showed a significantly higher score on the Beck Depression Inventory scale than the control group (32.97 ± 2.4 vs. 31.93 ± 2.3 vs. 8.00 ± 2.3 in all groups respectively) ( P -value < 0.001). Patients with bipolar depression and MDD showed a significantly higher serum CRP level than the control group (134.96 ± 16.45 vs. 133.86 ± 17.59 vs.56.04 ± 26.71 vs. in all groups respectively) ( P -value < 0.001). In all studied groups, elevated plasma CRP levels have a significant linear correlation with the severity of depression as measured by the Beck Depression Inventory (BDI) ( r = 0.887, P -value < 0.001).
Conclusions
Serum CRP levels are significantly higher in MDD and BD patients when compared to controls. Individuals with higher CRP levels had more severe depression, and this finding was significantly higher in women than in men.
... Within the innate immune system, several proinflammatory cytokines were studied. In general, depressed women showed higher interleukin (IL)-6 serum levels than depressed men ( Birur et al., 2017 ;Pallavi et al., 2015 ), but other findings demonstrate higher blood IL-6 levels in depressed males versus females, relative to respective controls ( Vogelzangs et al., 2012 ). Serum levels of other proinflammatory cytokines, such as IL-1 β and tumor necrosis factor alpha (TNF-α), positively correlated with depression severity and suicidal thoughts in depressed females, but not males, in relation to respective controls ( Birur et al., 2017 ). ...
... Among MDD patients, higher CRP serum levels associated with greater depressive symptoms and suicidality in women, but not in men ( Köhler-Forsberg et al., 2017 ). On the contrary, other findings showed associations between higher CRP levels and MDD diagnosis in men, but not in women, in relation to their respective controls ( Ramsey et al., 2016 ;Vogelzangs et al., 2012 ), and a similar association was found in a cohort of obese participants evaluated for depressive symptoms ( Vetter et al., 2013 ). ...
Major depressive disorder (MDD) presents different clinical features in women and men, with women being more affected and responding differently to antidepressant treatment. Specific molecular mechanisms underlying these differences are not well studied and this narrative review aims at providing an overview of the neurobiological features underlying sex-differences in biological systems involved in MDD pathophysiology and response to antidepressant treatment, focusing on human studies. The majority of the reviewed studies were performed through candidate gene approaches, focusing on biological systems involved in MDD pathophysiology, including the stress response, inflammatory and immune, monoaminergic, neurotrophic, gamma-aminobutyric acid and glutamatergic, and oxytocin systems. The influence of the endocrine system and sex-specific hormone effects are also discussed. Genome, epigenome and transcriptome-wide approaches are less frequently performed and most of these studies do not focus on sex-specific alterations, revealing a paucity of omics studies directed to unravel sex-based differences in MDD. Few studies about sex-related differences in antidepressant treatment response have been conducted, mostly involving the inflammatory system, with less evidence on the monoaminergic system and sparse evidence in omics approaches. Our review covers the importance of accounting for sex-differences in research, optimizing patient stratification for a more precise diagnostic and individualized treatment for women and men.
... Some somatic symptoms can be normalized via a successful AD treatment, which supports the idea that impaired neurotransmission may impact metabolic/redox mechanisms in depression. Concomitantly, dysfunctional arousal states can be linked to inadequate lifestyle and dietary habits, which damage the metabolism, nutritional conditions and antioxidant responses of depressed patients [12]. Recent evidence of changed brain-periphery cross-talks in depression is provided by the significant variations in hematological parameters, such as platelet counts, leukocyte (LK) formulas or their ratios, in MDD [13,14]. ...
This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.
... There is growing evidence that neuroinflammation is a potentially important contributor to the pathophysiology of depression [7]. Patients with chronic inflammation often have depressive symptoms [8], and high levels of inflammatory markers, such as interleukin-6 (IL- 6), have been found in MDD patients [9,10]. Microglia are the innate immune cells that settle in the brain and are critical to the development and progression of neuroinflammation [11], they are activated in response to tissue repairment and host defense against infectious stimuli [12]. ...
Background
Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200–CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown.
Methods
The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging.
Results
We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS.
Conclusions
Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.
... Our findings are also consistent with a large study in PWoH which found that men but not women with depression had elevated IL-6 (Vogelzangs et al., 2012). These results add to the evidence linking inflammation to depression in both PWH and PWoH. ...
Background:
Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex.
Methods:
Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities.
Results:
Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C-C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = -3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected.
Interpretation:
We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.
... 24 Conversely, others reported elevation in inflammatory markers posttreatment with both tricyclic antidepressants (TCAs) and serotonin noradrenaline reuptake inhibitors (SNRIs). 25,26 The diverse effects of antidepressants on levels of inflammatory makers may be due to differences in mechanisms of action: there is evidence that noradrenaline has pro-inflammatory effects on innate immune cells and thus potentiates cytokine production. 27 Atypical antipsychotics (AAPs) are recommended as augmentation treatments for MDD when patients do not respond to firstline SSRIs or SNRIs. ...
Objective
There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).
Methods
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.
Results
Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Conclusion
Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
... Females have consistently been found to have higher rates of MD starting at the onset of puberty (Slavich and Sacher, 2019;Hyde et al., 2008), with one potential reason for this difference being that females tend to have a greater pro-inflammatory response to immunological challenge. However, a greater inflammatory response has not been uniformly associated with greater depressive symptoms across males and females with some hypothesizing that sex-hormones play a contributing role (Epskamp et al., 2016;Moieni et al., 2015;Vogelzangs et al., 2012;Slavich and Sacher, 2019;Bekhbat and Neigh, 2018). Sex-hormones can bind to immune cells and lead to complex proand ant-inflammatory effects (Slavich and Sacher, 2019). ...
Background:
Efforts to improve treatment for adults with major depression (MD) and childhood maltreatment (CM) have identified inflammation as a potential target to improve health. Network models have emerged as a new way to understand the relationship between depressive symptoms and inflammation. However, none have accounted for the role of childhood maltreatment in the link between depressive symptoms and inflammation, or sex differences commonly found in these constructs.
Methods:
Data from two waves of the Midlife Development in the United States study were used in this study (N = 1917). The Center for Epidemiological Studies Depression (CES-D) scale and Childhood Trauma Questionnaire, and six inflammation markers served as nodes in an undirected psychometric network analysis. Edges between nodes were calculated using partial Spearman's correlation. Separate networks were modeled for males and females.
Results:
The total network revealed several associations between nodes of CM, MD, and inflammation, with emotional abuse having a strong association with somatic complaints. Network comparison testing revealed male-female network invariance, with several edge differences between male and female networks. Males and females showed differences in associations across inflammatory markers and depressive symptom clusters, particularly among somatic complaints and interpersonal difficulties.
Conclusions:
Specific associations between dimensions of inflammation, CM, and MD may represent important targets for treatment. Network models disaggregated by sex showed that males and females may have fundamentally different associations between these constructs, suggesting that future studies should consider sex-specific interventions.
