We read with great interest the recent article by Shin et al. (1). The authors leveraged the substantial Australian Genetics of Depression Study (AGDS) cohort to provide compelling evidence for the clinical and biological validity of the atypical depression subtype. Their integrative analysis of clinical features, polygenic scores (PGSs) for mental, metabolic, and circadian traits, and self-reported treatment outcomes is a significant contribution to the field. The particularly robust finding of an association between a genetic predisposition for eveningness (lower-chronotype PGS) and atypical depression, which persisted after adjustment for body mass index (BMI), is noteworthy and points to a potentially core, BMI-independent pathway.
Radically different