WHITE MATTER ABNORMALITIES AND COGNITIVE IMPAIRMENT IN BIPOLAR I DISORDER: A MULTI-STATE INVESTIGATION

Abstract Background Bipolar I disorder (BD-I) presents a formidable challenge to modern psychiatry, characterized by recurrent manic episodes and depressive states, often accompanied by cognitive dysfunction. Despite its clinical significance, the mechanistic underpinnings of cognitive impairment in BD-I remain obscure. Structural brain changes have been implicated as potential contributors to this cognitive burden. Aims & Objectives In this study, we examined the relationship between cognitive impairment and white matter abnormalities in distinct states of BD-I, shedding light on the neurobiological basis of cognitive deficits in this population. Method Our investigation involved 119 participants aged 18 to 45, comprising 66 healthy controls (HC) and 53 BD-I patients: 28 remission (r- BD), 10 manic (m-BD), and 15 depressive (d-BD). Comprehensive assessments were conducted, encompassing clinical evaluations, cognitive testing utilizing the MATRICS Consensus Cognitive Battery (MCCB), and diffusion tensor imaging (DTI). Subsequently, we performed intergroup comparisons, statistical analyses, and correlation studies to unravel the complex relationships within this paradigm. Results Our findings revealed compared to HC, r-BD individuals exhibited significant disparities in attention, processing speed, working memory, and executive function. Similarly, m-BD patients displayed cognitive deficits in processing speed, visuospatial memory, and executive function, and d-BD individuals in emotional intelligence. Notably, our DTI analyses demonstrated a shared neuropathological feature across all BD-I states, revealing a common decrease in fractional anisotropy (FA) within the corpus callosum trunk (CCT). Moreover, our analyses identified distinct correlations between cognitive performance and the FA values of the CCT in specific BD-I states. In r-BD, the CCT FA values correlated with various cognitive functions, such as Trail Making Test A (r=-0.586, p=0.001), Symbol Coding (r=0.434, p=0.021) and Maze Test (r=0.426, p=0.024). In d-BD, the CCT FA values were negatively associated with Mayer-Salovey-Caruso Emotional Intelligence Test (r=-0.672, p=0.006). In contrast, no such correlations were observed in m-BD. When all BD-I patients were considered together, emotional intelligence was inversely correlated with CCT FA values (r=-0.396, p=0.00). Discussion & Conclusion In conclusion, this study highlights the nuanced nature of cognitive impairment in BD-I across different states, with the most severe deficits observed during remission. Notably, white matter abnormalities within the corpus callosum trunk appear to be a consistent feature of BD-I, possibly contributing to the cognitive challenges faced by these individuals. Our findings offer valuable insights into the neural substrates of cognitive dysfunction in BD-I, with potential implications for targeted interventions to ameliorate cognitive deficits in this population. References JENSEN, J. H., KNORR, U., VINBERG, M., KESSING, L. V. &MISKOWIAK, K. W. 2016. Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder: Associations with functional abilities. J Affect Disord, 205, 378-386. POLETTI, S., BOLLETTINI, I., MAZZA, E., LOCATELLI, C., RADAELLI, D., VAI, B., MERALDI, E., COLOMBO, C. &BENEDETTI, F. 2015. Cognitive performances associate with measures of white matter integrity in bipolar disorder. J Affect Disord, 174, 342-52.TONDO, L., VÁ ZQUEZ, G. H. &BALDESSARINI, R. J. 2017. Depression and Mania in Bipolar Disorder. Current neuropharmacology, 15, 353-358.