Hidden scars in depression? Implicit and explicit self-associations following recurrent depressive episodes

To help explain the recurrent nature of major depressive disorder, we tested the hypothesis that depressive episodes and/or the duration of depressive symptoms may give rise to persistent dysfunctional implicit and/or more explicit self-associations, which in turn may place people at risk for the recurrence of symptoms. We therefore examined, in the context of the Netherlands Study of Depression and Anxiety, whether the strength of self-depressed associations at baseline was related to the number of past episodes (retrospective analysis; n = 666), and whether the duration of symptoms between baseline and follow-up predicted self-depressed associations at 2-year follow-up (prospective analysis; n = 726). The lifetime Composite International Diagnostic Interviews and Life Chart Interview were used to index the number of depressive episodes; the Implicit Association Test and its explicit equivalent were used to index self-associations. Consistent with the hypothesis that self-depressed associations strengthen following prolonged activation of negative self-associations during depressive episodes, individuals' implicit and explicit self-depressed associations correlated positively both with the number of prior depressive episodes at baseline and with the duration of depressive symptoms between baseline and 2-year follow-up. There was evidence that these relationships held, particularly in the prospective study, even when controlling for neuroticism and current depressive symptoms, whereas the retrospective relationship between number of episodes and implicit self-associations fell just short of significance

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain : partly masked by depressive and anxiety disorders

Peer reviewedPublisher PD

Implicit and Explicit Self-Esteem in Current, Remitted, Recovered, and Comorbid Depression and Anxiety Disorders: The NESDA Study

BACKGROUND: Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder (MDD) and anxiety disorders (AD). Further, it has been hypothesized that MDD and AD may result in a low ISE "scar" that may contribute to recurrence after remission. However, the available evidence provides no straightforward support for the relevance of low ISE in MDD/AD, and studies testing the relevance of discrepant SE even showed that especially high ISE combined with low ESE is predictive of the development of internalizing symptoms. However, these earlier findings have been limited by small sample sizes, poorly defined groups in terms of comorbidity and phase of the disorders, and by using inadequate indices of discrepant SE. Therefore, this study tested further the proposed role of ISE and discrepant SE in a large-scale study allowing for stricter differentiation between groups and phase of disorder. METHOD: In the context of the Netherlands Study of Depression and Anxiety (NESDA), we selected participants with current MDD (n = 60), AD (n = 111), and comorbid MDD/AD (n = 71), remitted MDD (n = 41), AD (n = 29), and comorbid MDD/AD (n = 14), recovered MDD (n = 136) and AD (n = 98), and never MDD or AD controls (n = 382). The Implicit Association Test was used to index ISE and the Rosenberg Self-Esteem Scale indexed ESE. RESULTS: Controls reported higher ESE than all other groups, and current comorbid MDD/AD had lower ESE than all other clinical groups. ISE was only lower than controls in current comorbid AD/MDD. Discrepant self-esteem (difference between ISE and ESE) was not associated with disorder status once controlling for ESE. LIMITATIONS: Cross-sectional design limits causal inferences. CONCLUSION: Findings suggest a prominent role for ESE in MDD and AD, while in comorbid MDD/AD negative self-evaluations are also present at the implicit level. There was no evidence to support the view that AD and MDD would result in a low ISE "scar"

Diet quality in persons with and without depressive and anxiety disorders

Objective: This study examines the association of depressive and anxiety disorders and their clinical characteristics (disorder type, severity, chronicity and clinical subtypes) with diet quality. Method: Data from 1634 adults (controls = 336, current disorder = 414, remitted = 886) were sourced from the 9-year follow-up of the Netherlands Study of Depression and Anxiety. Depressive and anxiety disorders were established with Composite International Diagnostic Interviews. Severity was measured with the Inventory of Depressive Symptomatology (IDS), Fear Questionnaire and the Beck Anxiety Inventory. Chronicity was measured with life-chart interviews expressed as percentage time with a disorder(s). Diet quality was evaluated using the Mediterranean Diet Score (MDS) and the Alternative Healthy Eating Index (AHEI). Results: Diet quality was significantly worse among subjects with a current disorder than among healthy controls. Subdividing subjects showed that those with concurrent depressive and anxiety disorders had the lowest diet quality score (MDS: β = −0.41 per SD, 95% Confidence interval (95%CI) = -0.60, −0.21; AHEI β = −0.22 per SD 95% CI = −0.42,-0.03). More chronic depression or anxiety disorders and increased severity in all participants showed a dose-response association with poorer diet quality. There was no distinct pattern between IDS items related to depression subtypes and diet quality. Conclusion: Diet quality is poorer in persons with depressive and anxiety disorders; in particular in those with comorbidity. The more severe and chronic the symptoms, the poorer the diet quality. Prospective studies are needed to confirm the direction of the relationship of depressive and anxiety disorders with diet quality and to examine whether improving diet quality could improve mental health

The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene

Background: The oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend these findings, we examined whether three literature-based OXTR SNPs (rs2254298, rs53576, rs2268498) interact with childhood maltreatment in the development of clinically diagnosed depression and anxiety disorders. Methods: We included 2567 individuals from the Netherlands Study of Depression and Anxiety. This sample consisted of 387 healthy controls, 428 people with a current or past depressive disorder, 243 people with a current or past anxiety disorder, and 1509 people with both lifetime depression and anxiety diagnoses. Childhood maltreatment was measured with both an interview and via self-report. Additional questionnaires measured depression and anxiety sensitivity. Results: Childhood maltreatment was strongly associated with both lifetime depression and anxiety diagnoses, as well as with depression and anxiety sensitivity. However, the OXTR SNPs did not moderate these associations nor had main effects on outcomes. Conclusions: The three OXTR gene SNPs did not interact with childhood maltreatment in predicting lifetime depression and anxiety diagnoses or sensitivity. This stresses the importance of replication studies with regard to OXTR gene variants in general populations as well as in clearly established clinical samples

Metabolomics Profile in Depression:A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity

Integrating proteomic, sociodemographic and clinical data to predict future depression diagnosis in subthreshold symptomatic individuals

Funder: Stanley Medical Research Institute (SMRI); doi: https://doi.org/10.13039/100007123Abstract: Individuals with subthreshold depression have an increased risk of developing major depressive disorder (MDD). The aim of this study was to develop a prediction model to predict the probability of MDD onset in subthreshold individuals, based on their proteomic, sociodemographic and clinical data. To this end, we analysed 198 features (146 peptides representing 77 serum proteins (measured using MRM-MS), 22 sociodemographic factors and 30 clinical features) in 86 first-episode MDD patients (training set patient group), 37 subthreshold individuals who developed MDD within two or four years (extrapolation test set patient group), and 86 subthreshold individuals who did not develop MDD within four years (shared reference group). To ensure the development of a robust and reproducible model, we applied feature extraction and model averaging across a set of 100 models obtained from repeated application of group LASSO regression with ten-fold cross-validation on the training set. This resulted in a 12-feature prediction model consisting of six serum proteins (AACT, APOE, APOH, FETUA, HBA and PHLD), three sociodemographic factors (body mass index, childhood trauma and education level) and three depressive symptoms (sadness, fatigue and leaden paralysis). Importantly, the model demonstrated a fair performance in predicting future MDD diagnosis of subthreshold individuals in the extrapolation test set (AUC = 0.75), which involved going beyond the scope of the model. These findings suggest that it may be possible to detect disease indications in subthreshold individuals up to four years prior to diagnosis, which has important clinical implications regarding the identification and treatment of high-risk individuals

Lipid Peroxidation and Depressed Mood in Community-Dwelling Older Men and Women

It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but\ud epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin\ud F2a (8-iso-PGF2a), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older\ud adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal\ud study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women\ud free of mobility disability. Urinary concentration of 8-iso-PGF2a was measured by radioimmunoassay methods and adjusted\ud for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/\ud or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men\ud presented higher urinary concentrations of 8-iso-PGF2a than non-depressed men even after adjustment for multiple\ud sociodemographic, lifestyle and health factors (p=0.03, Cohen’s d = 0.30). This association was not present in women\ud (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in\ud older men from a large sample of the general population. Further studies are needed to explore whether the modulation of\ud oxidative stress may break down the link between late-life depression and its deleterious health consequences