is consistent with the common presence of psychotic symptoms in patients with melancholic depression(46). Furthermore, previous findings from NESDA cohort showed that patients categorized as severe typical were more likely to be smoker(15;16;18); smoking is highly comorbid with psychiatric disorders, especially with schizophrenia, although the underlying biology is not well understood(47). For the atypical subtype, converging epidemiological evidence suggests a correlation with obesity and immuno-metabolic alterations(11;18;19). In the current study, atypical was associated with GPRS for BMI and triglycerides, particularly when based on SNPs strongly associated with traits at stringent significance threshold, suggesting the presence of loci of moderate effect. This is consistent with our previous findings showing the strong association between the FTO rs9939609-A variant and atypical MDD(20). When tested, the FTO-atypical association was also independent from BMI; similarly, in the current study the association of the best performing GPRS (Pt<0.0001) for BMI and triglycerides with atypical was reduced in effect size after controlling for BMI, but was still evident. Nevertheless, we decided not to adjust these analyses for BMI: our results of a shared genetic basis sustain indeed the hypothesis that atypical depression and BMI-related metabolic dysregulations may represent epiphenomenon stemming from the same pathophysiological mechanism, and adjusting
