Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses

Background: Bipolar disorder (BD) is often misdiagnosed or tardily detected, leading to inadequate treatment and devastating consequences. The identification of objective biomarkers, such as functional and structural brain abnormalities of BD might improve diagnosis and help elucidate its pathophysiology.

Methods: To identify neurobiological markers of BD, two meta-analyses, one of functional neuroimaging studies related to emotional processing and a second of structural whole-brain neuroimaging studies in BD were conducted in the present study. Conducting a literature search on studies published up to September 2009 we identified 28 studies that were eligible for the meta-analyses: 13 functional magnetic resonance imaging studies, related to emotional processing and 15 structural imaging studies using whole-brain voxel-based morphometry. Only studies comparing patients with bipolar disorder to healthy controls were considered. Data were extracted or converted to a single anatomical reference (Talairach space). The activation likelihood estimation technique was used to assess the voxel-wise correspondence of results between studies.

Results: In patients with BD, decreased activation and diminution of gray matter were identified in a cortical-cognitive brain network that has been associated with the regulation of emotions. By contrast, patients with BD exhibited increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses. The present study provides evidence for functional and anatomical alterations in BD in brain networks associated with the experience and regulation of emotions.

Conclusions: These alterations support previously proposed neurobiological models of BD and might represent valid neurobiological markers of the disorder. The specificity of these results to unipolar depression remains to be explored.