Imbalance of thalamocortical structural connectivity in adolescents with early-onset schizophrenia

Yonghui Xiang; Shuting Chen; Jinqiang Zhang; Guowei Wu; Xuan Ouyang; Zhening Liu; Chen Tan; Can Xu; Lange Zheng; Xinran Xu; Lena Palaniyappan; Weidan Pu

doi:10.1016/j.pnpbp.2025.111423

Imbalance of thalamocortical structural connectivity in adolescents with early-onset schizophrenia

Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jun 26:111423. doi: 10.1016/j.pnpbp.2025.111423. Online ahead of print.

Authors

Yonghui Xiang¹, Shuting Chen¹, Jinqiang Zhang², Guowei Wu³, Xuan Ouyang³, Zhening Liu³, Chen Tan¹, Can Xu¹, Lange Zheng¹, Xinran Xu¹, Lena Palaniyappan⁴, Weidan Pu⁵

Affiliations

¹ Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
² Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China. Electronic address: zhangjinqiang@csu.edu.cn.
³ Institute of Mental Health, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁴ Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
⁵ Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China. Electronic address: weidanpu@csu.edu.cn.

PMID: 40581176
DOI: 10.1016/j.pnpbp.2025.111423

Abstract

Background: Thalamocortical circuit imbalance, characterized by decreased prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity, has been well-documented in adult-onset schizophrenia. We have previously demonstrated functional imbalance of this circuit in adolescents with early-onset schizophrenia (EOS). We now investigate if this functional imbalance stems from the thalamocortical structural connectivity in EOS, to cement its relevance to the neurodevelopmental modeling of psychosis.

Methods: The study included 212 adolescents (145 EOS patients and 67 healthy controls). To further control the medication effect, the patients were divided into two subgroups (drug-naive vs drug-treated). Fourteen bilateral cortical regions of interest and bilateral thalamus were used as targets and seeds respectively for probabilistic tractography to quantify structural connectivity of the thalamocortical circuit.

Results: Compared to healthy controls, in EOS, structural connectivity of the thalamus with the dorsolateral prefrontal (dlPFC) and parietal cortices was decreased, while connectivity with the sensorimotor cortices was increased. We also observed an unexpected increase in connectivity of the medial prefrontal cortex (mPFC) with thalamus in EOS. The imbalance pattern was replicated in two subgroups regardless of medication status. Further correlation analysis showed that the thalamic hypoconnectivity with the dlPFC and the hyperconnectivity with the mPFC were both related with higher individual symptom burden in patients.

Conclusions: The functional thalamocortical circuit imbalance in adolescents with schizophrenia is underwritten by a similar imbalance in the structural connectivity. A specific thalamocortical structural hyperconnectivity involving the mPFC, previously unobserved in adult-onset cases, may contribute to the distinct clinical manifestations in EOS.

Keywords: DTI; Early-onset schizophrenia; Neurodevelopment; Structural connectivity; Thalamocortical circuit.