Cognitive phenotypes associated with familial risk for bipolar disorder in youth: A latent profile analysis and links to behavioral approach and inhibition systems.

BACKGROUND: People with a familial history for bipolar I disorder are at substantially elevated risk for developing the disorder, but the mechanisms underlying this risk remain unclear. We examined whether familial risk is associated with distinct neurocognitive phenotypes and whether these phenotypes are related to behavioral approach (BAS) and inhibition (BIS). METHODS: Participants were 180 youth with and without familial risk for bipolar I disorder. Latent profile analysis identified neurocognitive phenotypes based on scores from Cambridge Neuropsychological Test Automated Battery tasks. Multinomial logistic regression examined associations between familial risk and cognitive phenotype membership. Linear regression tested associations among phenotypes and BIS/BAS scores. Mediation analysis assessed whether cognitive phenotypes mediated associations between familial risk and motivational ratings. RESULTS: Four cognitive profiles were identified: Resilient, Slowed Reaction Time, Lower Working Memory, and Global Lower Performance. In adjusted pairwise comparisons, individuals in the Resilient compared with the Global Lower Performance profile were significantly less likely to have familial risk for bipolar disorder (OR = 0.2, p = 0.02). Other profiles were also less likely to have familial risk for bipolar disorder, but the association was not significant (p = 0.08). Familial risk was associated with lower BAS Drive overall; however, its indirect effect through the Global Lower Performance profile was positive and approached significance, suggesting a potential suppression pattern. CONCLUSION: Familial risk for bipolar I disorder may be associated with a cognitive phenotype characterized by global neurocognitive underperformance. Findings suggest that familial risk may influence motivational processes through multiple liability pathways.