Relationship between cortical thickness and serotonin 1A receptor binding in bipolar disorder

Deficits in cortical thickness have been a replicated finding in BD. Greater brain serotonin 1 A receptor (5HT1AR) binding has also been reported in BD, consistent with a disruption in serotonin signaling. Serotonin can cause a trophic effect on the cerebral cortex. 31 depressed participants with BD and 49 healthy volunteers (HVs) were included. PET imaging with [¹¹C]WAY100635 was obtained with a metabolite-corrected arterial input function. Radiotracer binding potential (BP_F) values were quantified within cortical regions. T1-weighted MRI scans were processed through Freesurfer 7.1.1, and cortical thickness values were quantified within a right caudal middle frontal region that had previously been shown to have deficits in BD. The previous results were replicated here, with lower cortical thickness in BD relative to HV's in the region. Cortical thickness in that region was inversely associated with BP_F of [¹¹C]WAY100635 in BD (F = 4.77; df = 1, 28; p = 0.037), but no association was found in HVs (F = 0.62; df = 1, 46; p = 0.44). Whole brain exploratory analyses were performed to examine vertex-wise associations between BP_F values and cortical thickness. Within BD participants, BP_F of [¹¹C]WAY100635 was inversely associated with right superior parietal cortical thickness, and positively associated in the right posterior cingulate cortex and the left entorhinal cortex. Mean cortical thickness values in the significant clusters did not differ between BD and HV groups. Within HVs, no clusters were associated between cortical thickness and BP_F of [¹¹C]WAY100635. These data are consistent with a model wherein disruptions in serotonin signaling lead to a loss of trophic effect on cortical tissue in BD. Associations between 5HT1AR binding and cortical thickness in BD are not limited to areas of cortical thickness deficits.