Brain gyrification in bipolar disorder: a systematic review of neuroimaging studies

Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Genetic variations have been involved in the risk of this disorder, including those mediating brain function and neurodevelopment. Early neurodevelopment and neuroprogression processes could be reflected in brain gyrification patterns and help optimize the prediction and diagnosis of such disorders that is often delayed. Previous neuroimaging studies using this measure in patients with bipolar disorder revealed controversial results. This systematic review aimed to summarize available neuroimaging investigations on gyrification in BD compared to healthy controls (HC) and/or other psychiatric groups. Fourteen studies including 733 patients with BD, 585 patients with schizophrenia (SCZ), 90 with schizoaffective disorder (SZA), and 1380 healthy subjects were identified. Overall, a heterogeneous pattern of gyrification emerged between patients with BD and HC. Interestingly, increased gyrification or no differences were also observed in patients with BD compared to those with the schizophrenia-spectrum disorders. Furthermore, relatives of patients with BD showed lower or no differences in gyrification compared to healthy subjects without a family history of affective illness. Differences in the design and in methodological approaches could have contributed to the heterogeneity of the findings. The current review supports an altered brain gyrification pattern that underlies the pathophysiology of BD spanning large anatomical and functional neural networks, associated with altered cognitive functioning, difficulties in processing and affective regulation, and clinical symptoms. Longitudinal studies are needed to test different bipolar phenotypes and pharmacological effects on gyrification.