Abnormal functional lateralization and cooperation in bipolar disorder are associated with neurotransmitter and...

Hemispheric lateralization and cooperation are essential for efficient brain function, and aberrations in both have been found in psychiatric disorders such as schizophrenia. This study investigated alterations in hemispheric lateralization and cooperation among patients with bipolar disorder (BD) and associations with neurotransmitter and cell-type density distributions to identify potential molecular and cellular pathomechanisms.

Sixty-seven BD patients and 127 healthy controls (HCs) were examined by resting-state functional MRI (rs-fMRI). Whole-brain maps of the autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) were constructed to reveal BD-specific changes in brain functional lateralization and interhemispheric cooperation, respectively. Spatial associations of regional AI and CFH abnormalities with neurotransmitter and cell-type density distributions were examined by correlation analyses.

Bipolar disorder patients exhibited higher AI values in left superior parietal gyrus, cerebellar right Crus I, and cerebellar right Crus II, and these regional abnormalities were associated with the relative densities (proportions) of oligodendrocyte precursor cells and microglia. Patients also exhibited lower CFH values in right inferior parietal gyrus, bilateral middle occipital gyrus, left postcentral gyrus, and bilateral cerebellar crus II, and these regional abnormalities were associated with the densities of serotonin 1A and dopamine D2 receptors, oligodendrocyte precursor cells, astrocytes, and neurons.

These findings indicate that abnormal functional lateralization and cooperation in BD with potential molecular and cellular basis.