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PubMed2026

Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.

Bipolar disorder's (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder-and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic-GABAergic gradient along the psychotic factor. BD's genetic architecture appears hierarchical-a general liability resolving into dimensions of course and comorbidity, beyond subtypes.

Journal Article↗

PubMed2025

Mediterranean and standard American diet consumption in psychosis and non-psychosis affective disorders groups: Symptoms and cognition.

UNLABELLED: Research supports an association between diet and health, and emerging evidence suggests that diet is associated with neuropsychiatric symptoms. However, no human study has examined an anti-inflammatory diet across rigorously defined psychiatric diagnoses and its associations with symptom severity and cognition. As inflammation is implicated in mental illness, we investigated adherence to the Mediterranean diet (MD), an anti-inflammatory diet, and the standard American diet (SAD), and examined cross-sectional relationships with psychiatric symptoms and cognition. METHOD: Participants included 54 individuals with psychotic disorders, 30 with non-psychosis affective disorders and 40 healthy controls. Participants underwent diagnostic interviews, PANSS symptom ratings, and MATRICS cognitive assessments. The self-report GBAQ was used to assess adherence to the MD versus SAD. RESULTS: The psychosis group was significantly more likely to consume the SAD than healthy controls (p = 0.007), with MD adherence predicting better working memory (r = 0.461, p < 0.001). In the non-psychosis affective disorders group, MD adherence predicted slower processing speed (r = -0.376, p = 0.049). In the non-psychosis affective disorders group, MD predicted reduced PANSS General Psychopathology scale (r = -0.449, p = 0.013), as well as the Activation (r = -0.362, p = 0.049), and Dysphoric Mood factors (r = -0.403, p = 0.027). DISCUSSION: This first-of-its kind study identified poor dietary choices in persons with psychosis, showing significantly lower symptoms and better cognition in association with the MD in transdiagnostic analyses. It supports the study of dietary interventions for prevention and treatment of psychiatric conditions.

Humans↗