Genetic and symptomatic risks associated with longitudinal brain morphometry in bipolar disorder

Offspring of parents with bipolar disorder (BD offspring) with subthreshold symptoms are particularly vulnerable to future disease onset, yet most of them remain clinically unaffected until adulthood, implicating potential compensatory processes. This longitudinal study (average 6-year follow-up) determined the brain surface features related to combined BD genetic and symptomatic risks, and tested whether the identified features related to mood disorder onset at follow-up. We found at baseline young BD offspring with subthreshold symptoms ( N = 49, age 17.4 ± 5.9 years) showed higher cortical thickness in widespread regions than non-BD offspring with subthreshold symptoms ( N = 47, age 16.9 ± 4.1 years), while those regions showed reduced cortical thickness in patients with BD ( N = 51, age 17.7 ± 1.5 years) than healthy controls ( N = 72, age 16.6 ± 3.3 years). Among those regions, the frontotemporal cortex showed reduced baseline cortical thickness among individuals who developed mood disorders at follow-up, compared with those who remained undiagnosed. Our findings provide important evidence on the brain surface features related to BD risk and potential compensatory processes.