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

Attentional bias for negative, positive, and threat words in current and remitted depression

Background The aim of this study was to improve our understanding of the underlying mechanisms in the maintenance of depression. We examined attentional bias (AB) for negative and positive adjectives and general threat words in strictly-defined clinical groups of participants with pure Major Depressive Disorder (MDD) without a history of anxiety disorders (AD), mixed MDD and AD, and remitted participants. Method We investigated both stimulus specificity and time course of AB in these groups, adopting a cross-sectional design. Data were drawn from the large scale Netherlands Study of Depression and Anxiety (NESDA), from which we selected all participants with pure current MDD without a history of AD (n = 29), all participants with current MDD and co-morbid AD(s) (n = 86), all remitted MDD participants (n = 294), and a comparison group without (a history of) MDD or ADs (n = 474). AB was measured with an Exogenous Cueing Task covering short and long presentation times (500 and 1250 ms) and 4 stimulus types (negative, positive, threat, neutral). Results Both traditional and trial level (dynamic) AB scores failed to show an AB for negative adjectives in participants with MDD or mixed MDD/AD. Specifically for long duration trials (1250 ms), remitted participants showed a larger AB traditional score (albeit the actual score still being negative) than the comparison group. The mixed MDD/AD group showed a higher trial-level AB score away from positive adjectives (1250 ms) than the comparisons. In addition, the mixed MDD/AD group showed higher and more variable trial-level AB scores away from short and towards longer presented general threat words together with a non-significant tendency to show less negative traditional AB scores for threat trials (500 ms) than the comparison group. Conclusions All in all, the findings do not corroborate the view that an AB towards negative or away from positive adjectives is critically involved in currently depressed individuals. Yet, the relatively high (less negative) AB score for negative adjectives in remitted individuals points to the possibility that an AB for negative information may be involved as a risk factor in the recurrence of MDD

Alcohol use disorders and the course of depressive and anxiety disorders

BACKGROUND: Inconsistent findings have been reported on the role of comorbid alcohol use disorders as risk factors for a persistent course of depressive and anxiety disorders. AIMS: To determine whether the course of depressive and/or anxiety disorders is conditional on the type (abuse or dependence) or severity of comorbid alcohol use disorders. METHOD: In a large sample of participants with current depression and/or anxiety (n = 1369) we examined whether the presence and severity of DSM-IV alcohol abuse or alcohol dependence predicted the 2-year course of depressive and/or anxiety disorders. RESULTS: The persistence of depressive and/or anxiety disorders at the 2-year follow-up was significantly higher in those with remitted or current alcohol dependence (persistence 62% and 67% respectively), but not in those with remitted or current alcohol abuse (persistence 51% and 46% respectively), compared with no lifetime alcohol use disorder (persistence 53%). Severe (meeting six or seven diagnostic criteria) but not moderate (meeting three to five criteria) current dependence was a significant predictor as 95% of those in the former group still had a depressive and/or anxiety disorder at follow-up. This association remained significant after adjustment for severity of depression and anxiety, psychosocial factors and treatment factors. CONCLUSIONS: Alcohol dependence, especially severe current dependence, is a risk factor for an unfavourable course of depressive and/or anxiety disorders, whereas alcohol abuse is not

Longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders

Objective To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Methods Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders. Multiple physical symptoms were measured at baseline (T1) and two-year follow-up (T2) by the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale. Recurrence of depressive and anxiety disorders was assessed at two-year (T2) and four-year (T4) follow-up with the Composite International Diagnostic Interview. Logistic Generalized Estimating Equations were used to examine associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Depressive (IDS-SR) and anxiety symptoms (BAI), and other relevant covariates were taken into account. Results Multiple physical symptoms were significantly associated with recurrence of depression (OR = 1.04, 95%CI = 1.00–1.08), anxiety (OR = 1.07, 95%CI = 1.03–1.12), and depressive or anxiety disorders (OR = 1.06, 95%CI = 1.02–1.10), on average over time. Odds ratios did not change substantially when the IDS-SR mood-cognition and BAI subjective scale were included as covariates. Conclusion The presence of multiple physical symptoms was positively related to recurrence of depressive and anxiety disorders, independent of depressive and anxiety symptoms. Knowledge of risk factors for recurrence of depressive and anxiety disorders, such as the presence of multiple physical symptoms, could provide possibilities for better targeting interventions to prevent recurrence

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