TY - JOUR
T1 - Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia
AU - Sun, Dandan
AU - Guo, Huiling
AU - Womer, Fay Y.
AU - Yang, Jingyu
AU - Tang, Jingwei
AU - Liu, Juan
AU - Zhu, Yue
AU - Duan, Jia
AU - Peng, Zhengwu
AU - Wang, Huaning
AU - Tan, Qingrong
AU - Zhu, Qiwen
AU - Wei, Yange
AU - Xu, Ke
AU - Zhang, Yanbo
AU - Tang, Yanqing
AU - Zhang, Xizhe
AU - Xu, Fuqiang
AU - Wang, Jie
AU - Wang, Fei
N1 - Funding Information:
The authors thank all the participants for their cooperation and are grateful for the support of Shenyang Mental Health Centre, Department of Psychiatry, First Affiliated Hospital of China Medical University, Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, and Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences. The authors gratefully acknowledge the support of Professor Schwarz with the GSK ‘rat97’ rat brain MRI + atlas template set used for this research. This work was funded by the National Science Fund for Distinguished Young Scholars (81725005 to FW), the National Natural Science Foundation Regional Innovation and Development Joint Fund (U20A6005 to FW), the Liaoning Education Foundation (Pandeng Scholar, FW), the China Postdoctoral Science Foundation (2018M640265 to DS), the National Natural Science Foundation of China (81630032 to QT), and the Youth Innovation Promotion Academy of Sciences (Y6Y0021004 to JW).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115763695&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01617-y
DO - 10.1038/s41398-021-01617-y
M3 - Article
C2 - 34580274
AN - SCOPUS:85115763695
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 495
ER -