Dataset Information

A validation of the diathesis-stress model for depression in Generation Scotland.

ABSTRACT: Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4919 individuals. We identified nominally significant positive GxE effects in the full cohort (R²?=?0.08%, p?=?0.049) and in women (R²?=?0.19%, p?=?0.017), but not in men (R²?=?0.15%, p?=?0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R²?=?0.15%, p?=?0.038; R²?=?0.16%, p?=?0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p?=?2.86?×?10^-4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (??=?0.082, p?=?0.016) but had a protective effect in women (??=?-0.061, p?=?0.037). This difference was nominally significant (p?=?0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.

SUBMITTER: Arnau-Soler A

PROVIDER: S-EPMC6338746 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A validation of the diathesis-stress model for depression in Generation Scotland.

Arnau-Soler Aleix A Adams Mark J MJ Clarke Toni-Kim TK MacIntyre Donald J DJ Milburn Keith K Navrady Lauren L Hayward Caroline C McIntosh Andrew A Thomson Pippa A PA

Translational psychiatry 20190118 1

Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to ...[more]

PMID: 30659167

Similar Datasets

Project description:Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD. Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure -Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively. Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype. Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Project description:The human brain's resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person's rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and then were assessed with standardized protocols of the Human Connectome Project. Data-driven clustering identified five groups of patients with distinct patterns of rsFC regardless of diagnosis. These groups were distinguished by rsFC networks that regulate specific biopsychosocial aspects of psychosis: sensory hypersensitivity, negative emotional balance, impaired attentional control, avolition, and social mistrust. The rsFc group differences were validated by independent measures of white matter microstructure, personality, and clinical features not used to identify the subjects. We confirmed that each connectivity group was organized by differential collaborative interactions among six prefrontal and eight other automatically-coactivated networks. The temperament and character traits of the members of these groups strongly accounted for the differences in rsFC between groups, indicating that configurations of rsFC are internal representations of personality organization. These representations involve weakly self-regulated emotional drives of fear, irrational desire, and mistrust, which predispose to psychopathology. However, stable outpatients with different diagnoses (bipolar or schizophrenic psychoses) were highly similar in rsFC and personality. This supports a diathesis-stress model in which different complex adaptive systems regulate predisposition (which is similar in stable outpatients despite diagnosis) and stress-induced clinical dysfunction (which differs by diagnosis).

Dataset Information

A validation of the diathesis-stress model for depression in Generation Scotland.

Publications

A validation of the diathesis-stress model for depression in Generation Scotland.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets