Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?

Background: Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM-first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC).

Methods: Cross-sectional study design using convenient sampling was employed. We recruited FEM ( = 25), HR ( = 25), and age-matched HC ( = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory.

Results: The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test-controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test-complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001).

Conclusions: Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.