Prevalence of Clinically Significant Neurocognitive Deficits in Unaffected First-degree Relatives of Bipolar Disorder Patients: A Cross-sectional Study using an Indian Standardized Battery

Abstract Background: Bipolar affective disorder (BPAD) is associated with enduring neurocognitive impairments, which may precede illness onset and represent potential endophenotypes. Studying unaffected first-degree relatives (FDRs) of BPAD patients can provide insights into heritable cognitive vulnerabilities. Aim: To estimate the prevalence of clinically significant neurocognitive impairments in unaffected FDRs of BPAD patients using a culturally validated Indian neuropsychological battery. Materials and Methods: This cross-sectional study included 60 unaffected FDRs of BPAD patients and 60 age-, gender-, and education-matched healthy controls. Cognitive domains assessed included verbal memory, processing speed, sustained attention, and executive function using subtests from the NIMHANS Neuropsychological Battery. Impairment was defined as performance ≥1.5 standard deviations below the control mean or ≥90 th percentile for time-based tasks. Results: FDRs exhibited significantly higher rates of impairment across all domains: delayed recall (42.1% vs. 5.0%, P < 0.001), processing speed (63.2% vs. 16.7%, P < 0.001), sustained attention – time (50.9% vs. 3.3%, P < 0.001), and executive function (17.5% vs. 1.7%, P = 0.002). Verbal memory and vigilance error rates were also elevated among FDRs. These deficits meet criteria for potential cognitive endophenotypes. Conclusion: Unaffected FDRs of BPAD patients show a high prevalence of clinically significant cognitive deficits, particularly in processing speed, sustained attention, and delayed memory. These findings support the role of cognitive impairments as heritable markers of vulnerability and underscore the need for early identification and preventive strategies in at-risk individuals.