In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder

Serotonin 1A (5-HT1A) receptors mediate serotonin trophic role in brain neurogenesis. Gray matter volume (GMV) loss and 5-HT1A receptor binding alterations have been identified in major depressive disorder (MDD). Here we investigated the relationship between 5-HT1A receptor binding and GMV in 40 healthy controls (HCs) and, for the first time, 47 antidepressant-free MDD patients using Voxel-Based Morphometry and [C-11]WAY100635 Positron Emission Tomography. Values of GMV and 5-HT1A binding (expressed as BPF, one of the types of binding potentials that refer to displaceable or specific binding that can be quantified in vivo with PET) were obtained in 13 regions of interest, including raphe, and at the voxel level. We used regression analysis within each group to predict GMV from BPF, while covarying for age, sex, total gray matter volume and medication status. In the HCs group, we found overall a positive correlation between terminal field 5-HT1A receptor binding and GMV, which reached statistical significance in regions such as hippocampus, insula, orbital prefrontal cortex, and parietal lobe. We observed a trend towards inverse correlation between raphe 5-HT1A autoreceptor binding and anterior cingulate GMV in both groups, and a statistically significant positive correlation between raphe 5-HT1A binding and temporal GMV in MDD. Analysis of covariance at the voxel-level revealed a trend towards interaction between diagnosis and raphe 5-HT1A binding in predicting GMV in cerebellum and supramarginal gyrus (higher correlation in HCs compared with MDD). Our results replicated previous findings in the normative brain, but did not extend them to the brain in MDD, and indicated a trend towards dissociation between MDD and HCs in the relationship of raphe 5-HT1A binding with postsynaptic GMV. These results suggest that 5-HT1A receptors contribute to altered neuroplasticity in MDD, possibly via effects predating depression onset.