Brain and cardiovascular responses to acute stress in remitted and recurrent late-life depression
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Genome-wide analysis identifies novel shared loci between depression and white matter microstructure
Depression, a complex and heritable psychiatric disorder, is associated with alterations in white matter microstructure, yet their shared genetic basis remains largely unclear. Utilizing the largest available genome-wide association study (GWAS) datasets for depression (N = 674,452) and white matter microstructure (N = 33,224), assessed through diffusion tensor imaging metrics such as fractional anisotropy (FA) and mean diffusivity (MD), we employed linkage disequilibrium score regression method to estimate global genetic correlations, local analysis of [co]variant association approach to pinpoint genomic regions with local genetic correlations, and conjunctional false discovery rate analysis to identify shared variants. Our findings revealed that depression showed significant local genetic correlations with FA in 37 genomic regions and with MD in 59 regions, while global genetic correlations were weak. Variant-level analysis identified 78 distinct loci jointly associated with depression (25 novel loci) and FA (35 novel loci), and 41 distinct loci associated with depression (17 novel loci) and MD (25 novel loci). Further analyses showed that these shared loci exhibited both concordant and discordant effect directions between depression and white matter traits, as well as distinct yet overlapping hemispheric patterns in their genetic architecture. Enrichment analysis of these shared loci implicated biological processes related to metabolism and regulation. This study provides evidence of a mixed-direction shared genetic architecture between depression and white matter microstructure. The identification of specific loci and pathways offers potential insights for developing targeted interventions to improve white matter integrity and alleviate depressive symptoms.
Depression symptom-specific genetic associations in clinically diagnosed and proxy case Alzheimer’s disease
Depression is a risk factor for the later development of Alzheimer’s disease (AD), but evidence for the genetic relationship is mixed. Assessing depression symptom-specific genetic associations may better clarify this relationship. To address this, we conducted genome-wide meta-analysis (a genome-wide association study, GWAS) of the nine depression symptom items, plus their sum score, on the Patient Health Questionnaire (PHQ-9) (GWAS-equivalent N: 224,535–308,421) using data from UK Biobank, the GLAD study and PROTECT, identifying 37 genomic risk loci. Using six AD GWASs with varying proportions of clinical and proxy (family history) case ascertainment, we identified 20 significant genetic correlations with depression/depression symptoms. However, only one of these was identified with a clinical AD GWAS. Local genetic correlations were detected in 14 regions. No statistical colocalization was identified in these regions. However, the region of the transmembrane protein 106B gene (TMEM106B) showed colocalization between multiple depression phenotypes and both clinical-only and clinical + proxy AD. Mendelian randomization and polygenic risk score analyses did not yield significant results after multiple testing correction in either direction. Our findings do not demonstrate a causal role of depression/depression symptoms on AD and suggest that previous evidence of genetic overlap between depression and AD may be driven by the inclusion of family history-based proxy cases/controls. However, colocalization at TMEM106B warrants further investigation.
Higher income is associated with greater life satisfaction, and more stress
Is there a cost to our well-being from increased affluence? Drawing upon responses from 2.05 million U.S. adults from the Gallup Daily Poll from 2008 to 2017 we find that with household income above ~$63,000 respondents are more likely to experience stress. This contrasts with the trend below this threshold, where at higher income the prevalence of stress decreases. Such a turning point for stress was also found for population sub-groups, divided by gender, race, and political affiliation. Further, we find that respondents who report prior-day stress have lower life satisfaction for all income and sub-group categories compared to the respondents who do not report prior-day stress. We find suggestive evidence that among the more satisfied, healthier, socially connected, and those not suffering basic needs deprivations, this turn-around in stress prevalence starts at lower values of income and stress. We hypothesize that stress at higher income values relates to lifestyle factors associated with affluence, rather than from known well-being deprivations related to good health and social conditions, which may arise even at lower income values if conventional needs are met.
Brain structural correlates of an impending initial major depressive episode
Neuroimaging research has yet to elucidate whether reported gray matter volume (GMV) alterations in major depressive disorder (MDD) exist already before the onset of the first episode. Recruitment of presently healthy individuals with a subsequent transition to MDD (converters) is extremely challenging but crucial to gain insights into neurobiological vulnerability. Hence, we compared converters to patients with MDD and sustained healthy controls (HC) to distinguish pre-existing neurobiological markers from those emerging later in the course of depression. Combining two clinical cohorts (n = 1709), voxel-based morphometry was utilized to analyze GMV of n = 45 converters, n = 748 patients with MDD, and n = 916 HC in a region-of-interest approach and exploratory whole-brain. By contrasting the subgroups and considering both remission state and reported recurrence at a 2-year clinical follow-up, we stepwise disentangled effects of (1) vulnerability, (2) the acute depressive state, and (3) an initial vs. a recurrent episode. Analyses revealed higher amygdala GMV in converters relative to HC (ptfce-FWE = 0.037, d = 0.447) and patients (ptfce-FWE = 0.005, d = 0.508), remaining significant when compared to remitted patients with imminent recurrence. Lower GMV in the dorsolateral prefrontal cortex (ptfce-FWE < 0.001, d = 0.188) and insula (ptfce-FWE = 0.010, d = 0.186) emerged in patients relative to HC but not to converters, driven by patients with acute MDD. By examining one of the largest available converter samples in psychiatric neuroimaging, this study allowed a first determination of neural markers for an impending initial depressive episode. Our findings suggest a temporary vulnerability, which in combination with other common risk factors might facilitate prediction and in turn improve prevention of depression.
Group arts interventions for depression and anxiety among older adults: a systematic review and meta-analysis
In this systematic review and meta-analysis, we assessed the efficacy of group arts interventions, where individuals engage together in a shared artistic experience (for example, dance or painting), for reducing depression and anxiety among older adults (> 55 yr without dementia). Fifty controlled studies were identified via electronic databases searched to February 2024 (randomised: 42, non-randomised: 8). Thirty-nine studies were included. Thirty-six studies investigated the impact of group arts interventions on depression (n = 3,360) and ten studies investigated anxiety (n = 949). Subgroup analyses assessed whether participant, contextual, intervention and study characteristics moderated the intervention–outcome relationship. Risk of bias was assessed with appropriate tools (RoB-2, ROBINS-1). Group arts interventions were associated with a moderate reduction in depression (Cohen’s d = 0.70, 95% confidence interval (CI) = 0.54–0.87, P < 0.001) and a moderate reduction in anxiety (d = 0.76, 95% CI = 0.37–1.52, P < 0.001), although there was publication bias in the depression studies. After a trim and fill adjustment, the effect for depression remained (d = 0.42; CI = 0.35–0.50; P < 0.001). Context moderated this effect: There was a greater reduction in depression when group arts interventions were delivered in care homes (d = 1.07, 95% CI = 0.72–1.42, P < 0.001) relative to the community (d = 0.51, 95% CI = 0.32–0.70, P < 0.001). Findings indicate that group arts are an effective intervention for addressing depression and anxiety among older adults.
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