Bipolar disorder has been hypothesized to, at least partially, be a neuroprogressive illness, characterized by worsening clinical features and potential brain changes over time. This neuroprogression hypothesis suggests that repeated mood episodes lead to cumulative structural and functional brain alterations, potentially exacerbating the course of the disorder. We have addressed this hypothesis through the extensive longitudinal St. Göran study, encompassing individuals with bipolar disorder and healthy controls. Study participants have been followed for up to 14 years, providing a long-term perspective on the neurobiological underpinnings of bipolar disorder.

This presentation will detail findings from repeated magnetic resonance imaging brain scans, biomarker investigations of cerebrospinal fluid, and assessments of cognitive performance. In the brain imaging studies, we find faster ventricular enlargement in bipolar disorder compared with controls, which provide partial support for neuroprogression. However, contrary to what might be expected under a neuroprogressive framework, we did not find accelerated cortical thinning in bipolar disorder, except in relation to manic episodes. Nor do we find accelerated worsening of cognitive performance in bipolar disorder compared with controls. Further, we do not detect signs of an Alzheimer-like neurodegeneration among individuals with bipolar disorder, although certain biomarkers associate with cognitive function. Taken together, our findings challenge some aspects of the neuroprogression theory.

The presentation will discuss these findings, exploring their implications for our understanding of the bipolar disorder pathophysiology and its impact on the brain and cognition over time. We will also consider the limitations of our data and propose directions for future investigations to further elucidate the pathophysiology bipolar disorder.