Novel implication of the prolactin (PRL) gene in the comorbidity of type 2 diabetes and depression

OBJECTIVE: The prolactin (PRL) system plays important behavioral, social, and metabolic roles, such as mediating social bonding and insulin secretion. Inherited dysfunction of the PRL pathway-related genes is associated with psychopathology and insulin resistance. We have previously suggested that the PRL system might be implicated in the comorbidity of psychiatric (depression) and type 2 diabetes (T2D) owing to the pleiotropy of PRL pathway-related genes. To our knowledge, no PRL variants have so far been reported in patients with either major depressive disorder (MDD) and/or T2D. PATIENTS AND METHODS: In this study, we analyzed 6 variants within the PRL gene and tested them for the presence of parametric linkage and/or linkage disequilibrium (LD, i.e., linkage and association) with familial MDD, T2D, and their comorbidity. RESULTS: We found, for the first time, that the PRL gene and its novel risk variants are linked to and in LD (i.e., linkage and association) with familial MDD, T2D, and MDD-T2D comorbidity. CONCLUSIONS: PRL might play a key role in mental-metabolic comorbidity and can be considered a novel gene in MDD and T2D.