• Guanqun Yao, Jingjing Pan, Ting Zou, Jing Li, Juan Li, Xiao He, Fuquan Zhang, and Yong Xu.
• Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, 030001, China.
• Bmc Med. 2024 Oct 23; 22 (1): 491491.

BackgroundFirst-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural-functional (SC-FC) coupling and transcriptional expression in FES.MethodsThis study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers.ResultsFES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case-control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes.ConclusionsThese findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia.© 2024. The Author(s).

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