Neurocognitive Vulnerability in First- Degree Relatives of Bipolar Patients: A Familial Risk Indicator?

Objective: To examine if first-degree relatives (FDRS) of individuals diagnosed with Bipolar I Affective Disorder (BPAD) exhibit cognitive deficits and to assess whether such deficits may indicate a hereditary vulnerability to the disorder.Methods: This cross-sectional comparative study was conducted at Index Medical College, Hospital & Research Centre, Indore, comprising 90 participants divided equally into three groups: 30 patients diagnosed with Bipolar I Disorder (BPAD), 30 first-degree relatives (FDRs) of these patients, and 30 healthy control subjects.The groups were matched for age, gender, and educational background.All participants underwent comprehensive neuropsychological evaluations using standardised instruments, including the Wisconsin Card Sorting Test (WCST), PGI Memory Scale, Trail Making Test (TMT), Stroop Colour and Word Test (Golden Version), and Letter Cancellation Test (LCT).Psychiatric conditions were systematically excluded in FDRs and control subjects through structured clinical interviews and administration of the General Health Questionnaire (GHQ-12).Quantitative scores from cognitive tests were statistically analysed using One-way ANOVA was used for normally distributed variables, and the Kruskal-Wallis H test for non-parametric comparisons among the three groups.for normally distributed data and Mann-Whitney U tests for non-parametric data, with significance set at p < 0.05.Results: First-degree relatives (FDRs) of bipolar patients exhibited statistically significant cognitive deficits compared to the healthy control group.Specifically, the FDRs demonstrated pronounced impairments in executive functions, including categorisation and conceptual-level responses on the Wisconsin Card Sorting Test (WCST; p < 0.001), which highlights challenges in cognitive flexibility and strategic planning.Additionally, they exhibited significant deficits in attentional processing speed on the Trail Making Test (TMT; p < 0.01) and memory functions, as measured by the PGI Memory Scale (p < 0.01). Conclusions:The cognitive deficits identified in asymptomatic first-degree relatives of patients with bipolar disorder potentially reflect an underlying familial or genetic vulnerability to the disorder.These findings emphasise the value of routine neuropsychological assessments among family members, enabling the identification of at-risk individuals and guiding the implementation of early preventative and intervention strategies for bipolar disorder.