Transl Psychiatry. 2025 Oct 31;15(1):445. doi: 10.1038/s41398-025-03659-y.
ABSTRACT
The mechanisms underlying the association between major depressive disorders (MDD) and obesity are still only partially understood. We aimed to explore these mechanisms using two approaches: 1) studying the parent-offspring transmission patterns of MDD and its subtypes and of the adiposity markers BMI and waist circumference, and 2) assessing the associations of parental polygenic risk scores (PRS) for MDD and BMI with MDD and adiposity markers in parents and offspring. Data on parents (N = 467) and their 18 to 35-year-old offspring (N = 592; mean age: 26.5 (s.d. 4.4) years) were derived from a community study conducted in an urban area. Psychiatric DSM-IV disorders including MDD and its atypical and melancholic subtypes were assessed using semi-structured diagnostic interviews. Phenotypic analyses provided evidence for a strong parent-child transmission of BMI (β = 0.33 kg/m2, 95% Confidence Intervals (CI): 0.24;0.42) and waist circumference (β = 0.28 cm, 0.19;0.38), but not for MDD or its subtypes or a cross-transmission of MDD and adiposity markers. Parental PRS for MDD were not only associated with MDD and its subtypes in parents, but also with BMI and waist circumference levels in parents (β = 0.49 kg/m2, 0.11;0.86; β = 2.00 cm, 1.05;3.00, respectively) and offspring (β = 0.54 kg/m2, 0.16;0.91; β = 1.27 cm, 1.17;2.37, respectively), whereas parental PRS for BMI were only associated with adiposity marker levels in parents and offspring. In conclusion, our findings relying on PRS suggest that the associations between atypical MDD and elevated adiposity marker levels may at least be partially attributable to common genetic liability. In contrast, the absence of parent-child transmission of MDD or its subtypes as well as the cross-transmission of MDD and adiposity markers according to our phenotypic analyses could be attributable to the young age of our offspring cohort.
PMID:41173844 | DOI:10.1038/s41398-025-03659-y
