Abnormal Thalamocortical Circuit in Adolescents With Early-Onset Schizophrenia

Manqi Zhang; Lena Palaniyappan; Mengjie Deng; Wen Zhang; Yunzhi Pan; Zebin Fan; Wenjian Tan; Guowei Wu; Zhening Liu; Weidan Pu

doi:10.1016/j.jaac.2020.07.903

Abnormal Thalamocortical Circuit in Adolescents With Early-Onset Schizophrenia

J Am Acad Child Adolesc Psychiatry. 2021 Apr;60(4):479-489. doi: 10.1016/j.jaac.2020.07.903. Epub 2020 Aug 10.

Authors

Affiliations

¹ Central South University, Changsha, Hunan, China; the Medical Psychological Institute of Central South University, Changsha, Hunan, China; and the National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
² Robarts Research Institute, University of Western Ontario, London, Ontario, Canada, and the Lawson Health Research Institute, London, Ontario, Canada.
³ The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Central South University, Changsha, Hunan, China; the Medical Psychological Institute of Central South University, Changsha, Hunan, China; and the National Clinical Research Center for Mental Disorders, Changsha, Hunan, China; National University of Defense Technology, Changsha, Hunan, China. Electronic address: weidanpu@csu.edu.cn.

PMID: 32791099
DOI: 10.1016/j.jaac.2020.07.903

Abstract

Objective: Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), although it is unclear whether this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset.

Method: A total of 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were used in functional connectivity analysis.

Results: The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the salience network (SN). In addition, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity.

Conclusion: Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the age of onset, raising the possibility of aberrant but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychosis seen in EOS.

Keywords: early-onset schizophrenia; fMRI; functional connectivity; thalamocortical connectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Brain Mapping
Cerebellum
Cerebral Cortex / diagnostic imaging
Humans
Magnetic Resonance Imaging
Neural Pathways / diagnostic imaging
Psychotic Disorders*
Schizophrenia* / diagnostic imaging
Thalamus / diagnostic imaging