A study explored whether familial risk for bipolar disorder and childhood-onset conditions like ADHD and anxiety contribute to distinct genetic profiles for mood disorder risk. The research followed 1065 participants, including 660 offspring of parents with bipolar disorder, using polygenic scores (PGS) to estimate genetic liability for conditions such as depression, bipolar disorder, ADHD, anxiety, neuroticism, and addiction. Mixed-effects and Cox regression models analyzed relationships between genetic profiles, childhood psychopathology, and mood disorder onset.

Results showed that in offspring of unaffected parents, higher PGS for ADHD and neuroticism were linked to ADHD and anxiety, respectively. Comorbid ADHD and anxiety increased PGS for neuroticism, ADHD, and bipolar disorder in the absence of familial risk. In offspring without familial risk, PGS for anxiety, depression, and neuroticism predicted mood disorder onset when ADHD and anxiety were present. PGS for addiction was also associated with mood disorder onset in those without familial risk. In offspring with familial risk, PGS for addiction predicted mood disorder onset only with comorbid ADHD and anxiety. These findings suggest a unique genetic basis for childhood-onset comorbidities in offspring with familial risk for bipolar disorder, contributing to mood disorder risk.

Reference: Freeman K, Zwicker A, Fullerton J, et al. Genetic contribution to developmental psychopathology in offspring with familial risk for bipolar disorder. Eur Neuropsychopharmacol. 2023;75(Suppl 1):S122. doi: 10.1016/j.euroneuro.2023.08.223.