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

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

The day-to-day bidirectional longitudinal association between objective and self-reported sleep and affect:An ambulatory assessment study

Background: Ambulatory assessments offer opportunities to evaluate daily dynamics of sleep and momentary affect using mobile technologies. This study examines day-to-day bidirectional associations between sleep and affect using mobile monitoring, and evaluates whether these associations differ between people without and with current or remitted depression/anxiety. Methods: Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176) or no (n = 90) CIDI depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective sleep duration (SD) and efficiency were obtained from actigraphy data. Self-reported SD, sleep quality (SQ), positive affect (PA) and negative affect (NA) were assessed by electronic diaries through EMA. Results: A bidirectional longitudinal association was found between self-reported SQ and affect, while no association was found for self-reported SD and objective SD and efficiency. Better SQ predicted affect the same day (higher PA: b = 0.035, p < 0.001; lower NA: b = -0.022, p < 0.001), while lower NA on the preceding day predicted better SQ (b = -0.102, p = 0.001). The presence of current depression/anxiety disorders moderated the association between better SQ and subsequent lower NA; it was stronger for patients compared to controls (p = 0.003). Limitations: Observational study design can only point to areas of interest for interventions. Conclusions: This 2-week ambulatory monitoring study shows that, especially among depression/anxiety patients, better self-reported SQ predicts higher PA and lower NA the same day, while lower NA predicts better self-reported SQ. The value of mobile technologies to monitor and potentially intervene in patients to improve their affect should be explored

Metabolomics signatures of depression:the role of symptom profiles

Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an "atypical/energy-related" symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An 'AES profile' score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10 -12), isoleucine (β = 0.13, p = 1.45*10 -10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10 -9) and saturated fatty acid levels (β = 0.09, p = 3.68*10 -10), and lower high-density lipoproteins cholesterol (β = -0.07, p = 1.14*10 -4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature-commonly linked to cardiometabolic disorders-associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression's detrimental impact on health. </p

Childhood trauma and dysregulation of multiple biological stress systems in adulthood:Results from the Netherlands Study of Depression and Anxiety (NESDA)

Background: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between CT and separate and cumulative activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), remains inconclusive. Methods: In the Netherlands Study of Depression and Anxiety (NESDA, n = 2778), we determined whether self-reported CT (as assessed by the Childhood Trauma Interview) was associated with separate and cumulative markers of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), the immune-inflammatory system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period) in adulthood. Results: Almost all individuals with CT (n = 1330) had either current or remitted depressive and/or anxiety disorder (88.6%). Total-sample analyses showed little evidence for CT being significantly associated with the separate or cumulative stress systems’ activity in adulthood. These findings were true for individuals with and without depressive and/or anxiety disorders. To maximize contrast, individuals with severe CT were compared to healthy controls without CT. This yielded slight, but significantly higher levels of cortisol awakening response (AUCg, β =.088, p =.007; AUCi, β =.084, p =.010), cumulative HPA-axis markers (β =.115, p =.001), C-reactive protein (β =.055, p =.032), interleukin-6 (β =.053, p =.038), cumulative inflammation (β =.060, p =.020), and cumulative markers across all systems (β =.125, p =.0003) for those with severe CT, partially explained by higher rates of smoking, body mass index, and chronic diseases. Conclusion: While our findings do not provide conclusive evidence on CT directly dysregulating stress systems, individuals with severe CT showed slight indications of dysregulations, partially explained by an unhealthy lifestyle and poorer health

Comparing Cognitive and Somatic Symptoms of Depression in Myocardial Infarction Patients and Depressed Patients in Primary and Mental Health Care

Depression in myocardial infarction patients is often a first episode with a late age of onset. Two studies that compared depressed myocardial infarction patients to psychiatric patients found similar levels of somatic symptoms, and one study reported lower levels of cognitive/affective symptoms in myocardial infarction patients. We hypothesized that myocardial infarction patients with first depression onset at a late age would experience fewer cognitive/affective symptoms than depressed patients without cardiovascular disease. Combined data from two large multicenter depression studies resulted in a sample of 734 depressed individuals (194 myocardial infarction, 214 primary care, and 326 mental health care patients). A structured clinical interview provided information about depression diagnosis. Summed cognitive/affective and somatic symptom levels were compared between groups using analysis of covariance, with and without adjusting for the effects of recurrence and age of onset. Depressed myocardial infarction and primary care patients reported significantly lower cognitive/affective symptom levels than mental health care patients (F (2,682) = 6.043, p = 0.003). Additional analyses showed that the difference between myocardial infarction and mental health care patients disappeared after adjusting for age of onset but not recurrence of depression. These group differences were also supported by data-driven latent class analyses. There were no significant group differences in somatic symptom levels. Depression after myocardial infarction appears to have a different phenomenology than depression observed in mental health care. Future studies should investigate the etiological factors predictive of symptom dimensions in myocardial infarction and late-onset depression patients

Metabolomic profiles discriminating anxiety from depression

Objective: Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations. Methods: Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites. Results: As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration. Conclusion: While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders