Dysfunctional neuroplasticity contributes to the pathogenesis of Alzheimer's disease, schizophrenia and depression. However, the underlying molecular mechanisms are not fully understood. Previous studies report neuromodulatory properties of the serotonin-1A (5-HT1A) receptor, which is also altered in these disorders. This suggests 5-HT1A mediated neuroplasticity as potential pathogenic factor.

The aim of this study was to demonstrate 5-HT1A mediated neuroplasticity in vivo.

We used positron emission tomography to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance imaging in 35 healthy subjects (mean 26.6 ±6.8 years; 17 women). Voxel-wise regression analysis was performed with gray matter volume (GMV) as dependent and 5-HT1A BPND as independent variable. Additionally, regression analysis was calculated with whole brain GMV as dependent variable and 5-HT1A BPND of the dorsal raphe nucleus (DRN) as independent variable. Control variables were age, sex and total GMV, respectively.

5-HT1A receptor density predicted GMV of the hippocampus, medial temporal cortex, inferior temporal cortex, medial occipital cortex and the pericalcarine region in each hemisphere (p < 0.05 false discovery rate corrected, R2: 0.308–0.503). These associations were independent from local numbers of neurons. Furthermore, 5−HT1A receptor levels in the DRN predicted GMV of the anterior cingulate cortex (p = 0.001, R2=0.656, uncorrected).

These results demonstrate 5-HT1A receptor mediated morphogenetic mechanisms in healthy human subjects' brains, which occur not only locally but also at the macro-network level. Finally, morphogenetic signaling investigated with multimodal neuroimaging could contribute to better understanding and diagnostic identification of gray matter loss in neuropsychiatric disorders.