Right-sided 5-HT4-RSMS was correlated with MRS glutamate ( R = 0.357, p = 0.048). Magnitudes of subfield volumetric reduction in FEP correlated most with 5-HT1A ( R = 0.64, p = 4.09E-03) and 5-HT4 ( R = 0.54, p = 0.02) densities as expected, and replicated using previously published data from two FEP studies. Gene expression indicated 5-HT1A and 5-HT4 to correlate with AMPA and NMDA expression, respectively. We found reduced hippocampal volumes in FEP, while CA4-dentate gyrus showed greatest reductions. Measures of individual hippocampal shape-receptor alignment were derived through normative modelling and correlations to receptor distributions, termed Receptor-Specific Morphometric Signatures (RSMS). We used gene expression data to correlate serotonin and glutamate receptor genes across the hippocampus. Automated methods delineated the hippocampus to map receptor density across subfields. We investigated hippocampal anomalies in first-episode psychosis (FEP) in relation to receptor distributions by leveraging 4 sources of data: (1) ultra high-field (7-Tesla) structural neuroimaging, and (2) proton magnetic resonance spectroscopy (1H-MRS) of glutamate from 27 healthy and 41 FEP subjects, (3) gene expression data from the Allen Human Brain Atlas and (4) atlases of the serotonin receptor system. Hippocampal atrophy is a well-established feature of schizophrenia, with select subfields hypothesized as particularly vulnerable due to variation in glutamate receptor densities. Disrupted serotonergic and glutamatergic signaling interact and contribute to the pathophysiology of schizophrenia, which is particularly relevant for the hippocampus where diverse expression of serotonin receptors is noted.
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