Altered volume of thalamic nuclei and genetic expression in first-episode psychotic patients, and their association with childhood adversity

Abstract

Childhood maltreatment is a significant risk factor for schizophrenia, and there are correlations between these adversities and thalamic gray matter density. The thalamus, a subcortical structure with various nuclei with specific connections, relays sensory information and participates in higher cognitive processes. Thalamic alterations are evident in psychotic disorders, and early-life adversities may affect its development, potentially contributing to psychosis. However, no evidence exists of volumetric alterations in thalamic nuclei in first-episode psychosis (FEP) patients related to early traumatic events. This study recruited 70 FEP patients and 68 age-matched healthy controls, who underwent 3 T structural MRI and clinical scales, including the Childhood Trauma Questionnaire (CTQ). The thalamus was analyzed for shape and segmented into nuclei to assess volume. Additionally, peripheral blood was analyzed for the expression of VCAN, CSGALNACT1, ST8SIA4, NRGN, SP4, and TOX genes, which are related to neuronal plasticity in the thalamus and psychosis. Results showed volumetric reductions in the whole thalamus and specific nuclei (lateral posterior, lateral geniculate, medial geniculate, ventrolateral, centromedian, anteroventral, mediodorsal, and pulvinar). The thalamus did not show shape alterations. A significant association was observed between physical neglect during childhood and the volume of the left thalamus and its anteroventral nucleus. Reduced expression of ST8SIA4 and SP4 genes was detected in FEP patients compared to healthy controls, with correlations between thalamic nuclei volumes and gene expression differing between groups. In conclusion, this study links thalamic nuclei volume with childhood adversities in FEP and highlights changes in ST8SIA4 and SP4 expression, correlating with thalamic nuclei volumes.

Keywords: Childhood adversity; First-episode psychosis; Gene expression; MRI; Thalamus.