High-resolution longitudinal changes in the cortical morphology of youth with family history of bipolar disorder

Background Individuals with a family history of bipolar disorder are at increased risk of developing affective psychopathology. Longitudinal imaging studies in young people with familial risk have been limited, and cortical developmental trajectories in the progression towards illness remain obscure. Aims To establish high-resolution longitudinal differences in cortical structure that are associated with risk of bipolar disorder. Method Using structural magnetic resonance imaging data from 217 unrelated ‘Bipolar Kids and Sibs study’ participants (baseline n = 217, follow-up n = 152), we examined changes over a 2-year period in cortical area, thickness and volume, measured at each vertex across the cortical surface. Groups comprised 105 ‘high-risk’ participants with a first-degree relative with bipolar disorder (female n = 64; age in years: M (mean) = 20.9, s.d. = 5.5) and 112 controls with no familial psychiatric history (females n = 60; age in years: M = 22.4, s.d. = 3.7). Results Accelerated thickness and volume reductions over time were observed in ‘high-risk’ individuals across multiple cortical regions, relative to controls, including right lateral orbitofrontal thickness ( β = 0.033, P < 0.001) and inferior frontal volume ( β = 0.021, P < 0.001). These differences were observed after controlling for age, sex, ancestry, current medication status, lifetime psychiatric diagnoses and measures of gross brain morphology. Conclusions Longitudinal group differences suggest the presence of thicker cortex in familial ‘high-risk’ individuals at earlier developmental stages, followed by accelerated thinning towards the typical age of bipolar disorder onset. Future examination of genetic and environmental components of familial risk and the mechanistic nature (pathological or protective) of cortical-trajectory differences over time may facilitate the identification of prodromal biomarkers and opportunities for early clinical intervention.