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Biomedical subjects

Friederike S David

Publications and source records attributed to Friederike S David.

2 recordsLinked to original sources
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↗
PubMed2026

Associations between CRP-related DNA methylation, stress exposure, and depression severity in a longitudinal clinical cohort.

BACKGROUND: Environmental adversity is linked to major depressive disorder (MDD), potentially via sustained low-grade inflammation. However, serum markers such as C-reactive protein (CRP) are transient and sensitive to acute states. In contrast, epigenetic signatures of inflammation may provide a more stable trace of how stress becomes biologically embedded and contributes to depression risk over time. METHODS: In a subsample of the Marburg-Münster Affective Disorders Cohort Study (MACS; N = 579; 320 healthy controls, 259 with MDD), we examined whether early life adversity (ELA; CTQ) and recent life stress (RLS; LEQ) are associated with CRP-related DNA methylation (CRPm) at baseline. We further tested whether CRPm predicts depressive symptom severity (HAMD) at baseline and at two-year follow-up (n = 407). DNA was extracted from whole blood, and CRPm scores were computed using publicly available genome-wide summary statistics. RESULTS: CRPm explained 21.3% of the variance in serum high-sensitivity CRP (hsCRP). Higher CRPm was significantly associated with both ELA (b = 0.01, SE = 0.003, p = 0.017) and RLS (b = 0.01, SE = 0.004, p = 0.032), after adjusting for age and sex. CRPm also predicted depressive symptom severity at baseline (b = 0.68, SE = 0.27, p = 0.013) and at follow-up (b = 0.79, SE = 0.25, p = 0.002). These associations remained after controlling for white blood cell-type composition but were attenuated after adjusting for BMI and smoking. In contrast, hsCRP was not associated with adversity or depressive symptoms. CONCLUSION: Our study indicates that a methylation-based index of chronic inflammation is associated with stress exposure and depressive symptoms over time, in contrast to fluctuating serum hsCRP. The findings are more consistent with an indirect pathway in which environmental adversity is linked to inflammatory biology via stress-related health behaviors, rather than with a model of direct biological embedding.

Humans↗