Study suggests genetic link between obesity, major depression
Phenotypic associations between atypical depression symptoms and obesity-related traits may be due to shared pathophysiologic mechanisms in major depressive disorder.
“In the past decade, evidence has emerged suggesting that the link between depression and immunometabolic dysregulations is stronger, or specific, for [major depressive disorder (MDD)] with atypical features, such as increased appetite and/or weight and hypersomnia,” Yuri Milaneschi, PhD, of Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, and colleagues wrote. “Other clinical characteristics linked to atypical depression are preponderance of female sex, earlier age at onset and higher severity.”
To determine genetic associations between major depression and atypical features of obesity-related immunometaoblic dysregulations, researchers analyzed data from case-control, cohort and population-based studies for 26,628 participants with established psychiatric diagnoses and genome-wide genotype data. BMI data were available for 15,237 participants.
Overall, 11,837 participants had MDD. Of these, 5,347 (45.2%) had decreased appetite and/or weight and 1,871 (15.8%) had increased appetite and/or weight.
Common genetic variants explained approximately 10% of heritability in appetite and/or weight subgroups.
There was a strong positive genetic correlation between increased appetite and/or weight and BMI and an inverse correlation between decreased appetite and/or weight and BMI.
Participants with decreased appetite and/or weight had a higher polygenic risk for increased BMI (OR = 1.18; 95% CI, 1.12-1.25), C-reactive protein levels (OR = 1.08; 95% CI, 1.02-1.13) and leptin levels (OR = 1.09; 95% CI, 1.06-1.12).
There are some limitations to the study findings, according to Roseann E. Peterson, PhD, of Virginia Commonwealth University, Richmond. These include group assignment based on a single MDD episode and inclusion of only European cohorts.
“Despite these limitations, leveraging molecular genetic techniques and taking advantage of large-scale consortia data has permitted Milaneschi et al to advance our understanding of the MDD-BMI association,” she wrote in an accompanying editorial. “Crucially, their results highlight the value of clinical phenotyping and the importance of collecting symptom-level data to tackle clinical and etiological heterogeneity in complex psychiatric illnesses. Because of advances in quantitative genetic methodology, the utility of genetic data now goes beyond gene mapping efforts.” – by Amanda Oldt
Disclosures: Milaneschi and Peterson report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.