Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia

Dandan Sun, Huiling Guo, Fay Y. Womer, Jingyu Yang, Jingwei Tang, Juan Liu, Yue Zhu, Jia Duan, Zhengwu Peng, Huaning Wang, Qingrong Tan, Qiwen Zhu, Yange Wei, Ke Xu, Yanbo Zhang, Yanqing Tang, Xizhe Zhang, Fuqiang Xu, Jie Wang, Fei Wang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Schizophrenia (SZ) is a neurodevelopmental disorder. There remain significant gaps in understanding the neural trajectory across development in SZ. A major research focus is to clarify the developmental functional changes of SZ and to identify the specific timing, the specific brain regions, and the underlying mechanisms of brain alterations during SZ development. Regional homogeneity (ReHo) characterizing brain function was collected and analyzed on humans with SZ (hSZ) and healthy controls (HC) cross-sectionally, and methylazoxymethanol acetate (MAM) rats, a neurodevelopmental model of SZ, and vehicle rats longitudinally from adolescence to adulthood. Metabolomic and proteomic profiling in adult MAM rats and vehicle rats was examined and bioanalyzed. Compared to HC or adult vehicle rats, similar ReHo alterations were observed in hSZ and adult MAM rats, characterized by increased frontal (medial prefrontal and orbitofrontal cortices) and decreased posterior (visual and associated cortices) ReHo. Longitudinal analysis of MAM rats showed aberrant ReHo patterns as decreased posterior ReHo in adolescence and increased frontal and decreased posterior ReHo in adulthood. Accordingly, it was suggested that the visual cortex was a critical locus and adolescence was a sensitive window in SZ development. In addition, metabolic and proteomic alterations in adult MAM rats suggested that central carbon metabolism disturbance and mitochondrial dysfunction were the potential mechanisms underlying the ReHo alterations. This study proposed frontal-posterior functional imbalance and aberrant function developmental patterns in SZ, suggesting that the adolescent visual cortex was a critical locus and a sensitive window in SZ development. These findings from linking data between hSZ and MAM rats may have a significant translational contribution to the development of effective therapies in SZ.

Original languageEnglish
Article number495
JournalTranslational psychiatry
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

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