Abnormal Brain Network Interaction Associated With Positive Symptoms in Drug-Naive Patients With First-Episode Schizophrenia

Liu Yuan; Xiaoqian Ma; David Li; Zongchang Li; Lijun Ouyang; Lejia Fan; Zihao Yang; Zhenmei Zhang; Chunwang Li; Ying He; Xiaogang Chen

doi:10.3389/fpsyt.2022.870709

Abnormal Brain Network Interaction Associated With Positive Symptoms in Drug-Naive Patients With First-Episode Schizophrenia

Front Psychiatry. 2022 May 17:13:870709. doi: 10.3389/fpsyt.2022.870709. eCollection 2022.

Authors

Liu Yuan^{1

2}, Xiaoqian Ma^{1

2}, David Li^{1

2}, Zongchang Li^{1

2}, Lijun Ouyang^{1

2}, Lejia Fan^{1

2}, Zihao Yang^{1

2}, Zhenmei Zhang^{1

2}, Chunwang Li³, Ying He^{1

2}, Xiaogang Chen^{1

2}

Affiliations

¹ Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
² Mental Health Institute of Central South University, China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China.
³ Department of Radiology, Hunan Children's Hospital, Changsha, China.

Abstract

Positive symptoms are marked features of schizophrenia, and emerging evidence has suggested that abnormalities of the brain network underlying these symptoms may play a crucial role in the pathophysiology of the disease. We constructed two brain functional networks based on the positive and negative correlations between positive symptom scores and brain connectivity in drug-naive patients with first-episode schizophrenia (FES, n = 45) by using a machine-learning approach (connectome-based predictive modeling, CPM). The accuracy of the model was r = 0.47 (p = 0.002). The positively and negatively associated network strengths were then compared among FES subjects, individuals at genetic high risk (GHR, n = 41) for schizophrenia, and healthy controls (HCs, n = 48). The results indicated that the positively associated network contained more cross-subnetwork connections (96.02% of 176 edges), with a focus on the default-mode network (DMN)-salience network (SN) and the DMN-frontoparietal task control (FPT) network. The negatively associated network had fewer cross-subnetwork connections (71.79% of 117 edges) and focused on the sensory/somatomotor hand (SMH)-Cingulo opercular task control (COTC) network, the DMN, and the visual network with significantly decreased connectivity in the COTC-SMH network in FES (FES < GHR, p = 0.01; FES < HC, p = 0.01). Additionally, the connectivity strengths of the right supplementary motor area (SMA) (p < 0.001) and the right precentral gyrus (p < 0.0001) were reduced in FES. To the best of our knowledge, this is the first study to generate two brain networks associated with positive symptoms by utilizing CPM in FES. Abnormal segregation, interactions of brain subnetworks, and impaired SMA might lead to salience attribution abnormalities and, thus, as a result, induce positive symptoms in schizophrenia.

Keywords: CPM; brain network; positive symptoms; schizophrenia; segregation.