Neural Activity Alterations and Their Association With Neurotransmitter and Genetic Profiles in Schizophrenia: Evidence From Clinical Patients and Unaffected Relatives.

Shu Xiao, Pan Chen, Ting Su, Yanbin Jia, Li Huang, Shilin Sun, Ying Wang, Chao Chen, Zixuan Guo, Xinyue Tang, Guanmao Chen, Ruoyi Chen, Jiaying Gong, Zibin Yang

Journal: CNS neuroscience & therapeutics 2025;31(2):e70218

PMID: 39924342

Free Full Text on PubMed Central View on PubMed

Abstract

BACKGROUND

The pattern of abnormal resting-state brain function has been documented in schizophrenia (SCZ). However, as of yet, it remains unclear whether this pattern is of genetic predisposition or related to the illness itself.

METHODS

A systematical meta-analysis was performed to identify resting-state functional differences in probands and their high-risk first-degree relatives of schizophrenia (FDRs-SCZ) using Seed-based d Mapping software. Subsequently, spatial associations between postmortem gene expression and neurotransmitters distribution data and neural activity alterations were conducted to uncover neural mechanisms underlaying FDRs-SCZ and SCZ from a multidimensional perspective.

RESULTS

A total of 13 studies comprising 503 FDRs-SCZ and 605 healthy controls (HCs) and 129 studies comprising 6506 patients with SCZ and 6982 HCs were included. Compared to HCs, FDRs-SCZ displayed increased spontaneous functional activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC); patients with SCZ showed decreased spontaneous functional activity in the bilateral ACC/mPFC, bilateral postcentral gyrus, and right middle temporal gyrus as well as increased spontaneous functional activity in the bilateral striatum. The altered functional activity in FDRs-SCZ and SCZ shared similar spatial associations with genes enriched in potassium ion transmembrane transport, channel activity, and complex. The FDRs-SCZ and SCZ-related brain functional patterns were additionally associated with dopaminergic, serotonergic, and cholinergic neurotransmitter distribution.

CONCLUSIONS

SCZ-related resting-state functional, neuroimaging transcriptomes, and neurotransmitters abnormalities may exist in high-risk unaffected FDRs-SCZ, rather than just in overt SCZ. The study extended the evidence that altered brain function, along with their spatial correlations to genetics and neurotransmitter systems, may associate with genetic vulnerability for SCZ.

Address: Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China.; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.; Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.; Department of Radiology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.; Department of Radiology, Six Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.; Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou, China.

DOI: 10.1111/cns.70218

Link outs

Free resources

Full Text Sources:

https://pmc.ncbi.nlm.nih.gov/articles/pmid/3992434...

Medical:

https://medlineplus.gov/schizophrenia.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Schizophrenia, Neurotransmitter Agents, Brain, Family, Male, Female