FUNDO – Functional relevance of white matter abnormalities in bipolar disorder development

Bipolar disorders are characterized by high heritability. In most cases, this poses an immense burden not only on patients, yet also on relatives and the society. The substantial heritability of this mental disorder suggests a central role of neurobiological mechanisms in its aetiology. Identifying these mechanisms would facilitate earlier and improved diagnostics and foster the development of prevention. Yet, current knowledge on the neurobiological foundation of bipolar disorder is still insufficient. Two decades of research consolidated a consensual model, which postulates abnormal structural and functional changes in a neural network which is significantly involved in emotional processing and control. The ventral prefrontal cortex and the amygdala are central clusters of this network. It is assumed that these abnormal changes are caused by an impaired development of white matter (e.g. due to reduced myelinization of axons). This in turn forms the basis of manic or depressive episodes based on unstable biological processes. Indeed, there are studies reporting abnormal microstructural changes of white matter in patients with bipolar disorders, mainly in fronto-limbic and inter-hemispheric connections. Similar changes can be observed in healthy individuals with elevated (genetic) risks for bipolar disorders. Hence, it can be hypothesized that this poses a vulnerability marker for bipolar disorders. The missing link between this neurobiological finding in patients with bipolar disorders and functionally relevant indices like e.g. cognitive dysfunctions, which predict rates of employment and of clinical improvement, poses a substantial research gap. A second gap in current research is the insufficient understanding of histological and molecular processes underlying the observed white matter alterations. In order to close these gaps, the present project examines bipolar patients after their first bipolar episode and after a chronic course of the disease, as well as healthy individuals with and without elevated risks for bipolar disorders regarding microstructural alterations in white matter and respective associations with cognitive functions and emotional dysregulation. In order to precisely characterize abnormal white matter alterations and their underlying biological mechanisms, new acquisition and analysis methods of diffusion imaging with different magnetic field strengths (3 tesla, 7 tesla) are employed.

Duration of study:
January 2016 – January 2019

Deutsche Forschungsgemeinschaft

Prof. Dr. Michèle Wessa (principal investigator),
Dr. Eva Elisa Schneider

In cooperation with: Josselin Houenou, Institut national de la santé et de la recherche médicale, Saclay, Frankreich