FUnctional relevance of white matter abnormalities in bipolar DisOrder development

• Applicant: Professorin Dr. Michèle Wessa
• Subject Area: Personality Psychology, Clinical and Medical Psychology, Methodology ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Human Cognitive and Systems Neuroscience
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259172556

Bipolar disorder (BD) is a highly heritable mental disorder that ranks amongst the ten most significant reasons of disability worldwide and that causes immense burden on patients, family members and national health systems. The high heritability of BD suggests a major contribution of neurobiological mechanisms to the development of the disorder and their identification would improve possibilities of earlier and more accurate diagnosis as well as the development of effective preventions and interventions to alleviate the course of the disease. However, our understanding of the neurobiological mechanisms underlying BD development, are still incomplete. From two decades of research a neurobiological consensus model of BD has emerged, assuming abnormalities in the structure and function of an emotional processing and control network, including as key structures the ventral prefrontal cortex and the amygdala. It has been proposed that these abnormalities origin from disturbances in early white matter development, e.g., reduced myelination of axons and reduced prefrontal pruning, providing a basis for the development of manic or depressive episodes in the light of, e.g., stressful life events, triggering unstable biological processes. Indeed, abnormalities in white matter integrity in fronto-limbic and inter-hemispheric fiber tracts have been observed in BD patients and also in healthy individuals at higher risk to develop BD, suggesting that white matter abnormalities indeed play a role in the development of the disorder and represent a vulnerability marker of BD. However, one major shortcoming of current research is the missing link between findings of reduced white matter integrity in BD patients and functionally relevant outcomes, such as neuropsychological functioning that predicts, for example, favorable employment outcomes and recovery rates. Another shortcoming is the lack of histological understanding of the DTI results, which precludes us from understanding the molecular mechanisms of white matter alterations in BD. To overcome these limitations the present project will carefully characterize first-episode and chronic patients with bipolar-I disorder as well as healthy individuals at risk to develop BD with respect to white matter macro- and microstructure by means of advanced diffusion tensor imaging methods and with respect to neuropsychological functioning as well as emotional dysregulation as two hallmark features of BD. The overarching goals of the present study are (1) to relate neurobiological and neuropsychological measures and thereby to determine the relevance of white matter alterations for disturbed cognitive functioning and emotional dysregulation in BD; (2) to elucidate on mechanisms underlying white matter abnormalities in BD patients; (3) to delineate the role of white matter abnormalities and neuropsychological impairments in the development of BD and in the course of the disease.

• DFG Programme: Research Grants
• International Connection: France
• Participating Person: Dr. Josselin Houenou