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Thalamic Subregion Alterations and Short-Chain Fatty Acids in Schizophrenia and Ultra-High-Risk Individuals: A
Huiqing Peng1,2, Xiaogang Chen1,2, Ying He1,2
1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan, China.
Background:
Thalamic abnormalities have been implicated in schizophrenia, but their early role remains unclear. This study investigated structural and functional alterations of thalamic subregions in drug-naïve first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, and explored their associations with serum short-chain fatty acids (SCFAs).
Methods:
This cross-sectional study included 102 FES patients, 72 UHR individuals, and 69 healthy controls (HCs). Structural magnetic resonance imaging (MRI) data were available for all participants, and functional MRI and SCFA measurements were conducted in subgroups (functional MRI (fMRI): 76 FES, 63 UHR, 61 HC; SCFA: 59 FES, 51 UHR, 40 HC).
Results:
Thalamic volume was smaller in FES compared to HCs, with atrophy present specifically at the psychotic stage, particularly affecting the right thalamus and nuclei including the mediodorsal medial magnocellular (MDm), ventromedial (VM), and ventral posterolateral (VPL). Functional connectivity (FC) disruptions were observed in the left sensory thalamus with cortico-striatal-thalamic circuits and in the right occipital thalamus with fronto-temporal regions. Thalamic volumetric deficits correlated with negative and disorganized symptoms in both clinical groups. Serum SCFAs showed several significant associations: in the UHR group, FC between the right occipital thalamus and the left medial frontal cortex was negatively associated with acetic acid and total SCFA levels; in FES patients, centromedian nucleus volume was positively correlated with acetic acid; and in HCs, butyric acid was inversely correlated with the volume of the mediodorsal (MD) lateral nucleus.
Conclusions:
These findings highlight early thalamic subregional alterations in psychosis risk and co-occurring changes in gut-derived metabolites. Whether and how these changes are related remains a question for future research.
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