Longitudinal changes in neurocognitive functioning over two years in young people at increased genetic risk of bipolar disorder.

Background: Deficits in neurocognitive abilities are present in individuals with bipolar disorder (BD) and their unaffected first-degree relatives. However, limited research has examined changes in neurocognitive deficits over time in young people at increased genetic risk of BD.

Method: Neurocognition was evaluated at baseline in 180 young unaffected individuals (aged 12-30 years) at high familial risk of BD (HR), 70 patients with BD, and 130 controls. After two-year follow-up, neurocognition was reassessed in 132 HR participants and 102 controls.

Results: At baseline, the HR and BD groups demonstrated deficits in response inhibition and attention relative to controls. Over the follow-up period, baseline impairments in the Affective Go/No-Go task in the HR group remained persistent except for errors of omission towards positive valence stimuli, where impairment found at baseline improved over time, relative to controls (P = 0.001). During response inhibition to negative stimuli, HR participants who developed BD showed an impairment at baseline but improved over time, relative to those HR subjects who remained well and controls (P = 0.025); this effect was more pronounced in those who converted to threshold BD.

Limitations: While our study is well powered for whole group comparisons, the HR sub-group analyses were under-powered.

Conclusion: Neurocognitive baseline impairments in HR individuals remained largely persistent over time, with one response inhibition condition showing some improvement over time in those who developed BD. Our findings highlight the importance of stratifying HR cohorts and suggest impaired response inhibition may represent a quantitative endophenotype that differentiates those who transition to BD.