White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study

Abstract Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis, and its early identification is key to early intervention. Previous studies have suggested that disturbances in the frontal–striatal–thalamic (FST) circuit may play a role in the neuropathology of APSS. Howeve...

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Main Authors: Zhenzhu Chen, Qijing Bo, Lei Zhao, Yushen Ding, Yimeng Wang, Qitong Jiang, Feng Li, Yuan Zhou, Chuanyue Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Schizophrenia
Online Access:https://doi.org/10.1038/s41537-025-00635-9
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author Zhenzhu Chen
Qijing Bo
Lei Zhao
Yushen Ding
Yimeng Wang
Qitong Jiang
Feng Li
Yuan Zhou
Chuanyue Wang
author_facet Zhenzhu Chen
Qijing Bo
Lei Zhao
Yushen Ding
Yimeng Wang
Qitong Jiang
Feng Li
Yuan Zhou
Chuanyue Wang
author_sort Zhenzhu Chen
collection DOAJ
description Abstract Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis, and its early identification is key to early intervention. Previous studies have suggested that disturbances in the frontal–striatal–thalamic (FST) circuit may play a role in the neuropathology of APSS. However, the evidence regarding white matter structure remains fragmented. This study aimed to systematically investigate white matter (WM) alterations within the FST circuits in individuals with APSS. Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FMRIB Software Library software. The Brainnetome Atlas was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the FST circuit. The connection probability (CP) and diffusion index values were compared between the APSS and HC groups using the two-sample t test. Compared to HCs, individuals with APSS exhibited significantly lower CP values in right orbital gyrus_area 13- right nucleus accumbens (OrG_A13-NAC) fiber tract; higher mean diffusivity values in the left OrG_A13-NAC and left ventral caudate–left caudal temporal thalamus (vCa-cTtha) fiber tracts; higher radial diffusivity values in the right OrG_A13-NAC fiber tract; and higher axial diffusivity values in multiple frontal lobe ROI–striatum ROI and striatum ROI–thalamus ROI fiber tracts. Overall, individuals with APSS demonstrated white matter microstructural abnormalities, especially in the OrG_A13-NAC fiber tracts. These alterations may contribute to our understanding on the neuropathology of APSS.
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spelling doaj-art-8f0a4215b6cf46fcaff786d7aa96bc432025-08-20T02:10:32ZengNature PortfolioSchizophrenia2754-69932025-06-011111810.1038/s41537-025-00635-9White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography studyZhenzhu Chen0Qijing Bo1Lei Zhao2Yushen Ding3Yimeng Wang4Qitong Jiang5Feng Li6Yuan Zhou7Chuanyue Wang8The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical UniversityAbstract Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis, and its early identification is key to early intervention. Previous studies have suggested that disturbances in the frontal–striatal–thalamic (FST) circuit may play a role in the neuropathology of APSS. However, the evidence regarding white matter structure remains fragmented. This study aimed to systematically investigate white matter (WM) alterations within the FST circuits in individuals with APSS. Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FMRIB Software Library software. The Brainnetome Atlas was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the FST circuit. The connection probability (CP) and diffusion index values were compared between the APSS and HC groups using the two-sample t test. Compared to HCs, individuals with APSS exhibited significantly lower CP values in right orbital gyrus_area 13- right nucleus accumbens (OrG_A13-NAC) fiber tract; higher mean diffusivity values in the left OrG_A13-NAC and left ventral caudate–left caudal temporal thalamus (vCa-cTtha) fiber tracts; higher radial diffusivity values in the right OrG_A13-NAC fiber tract; and higher axial diffusivity values in multiple frontal lobe ROI–striatum ROI and striatum ROI–thalamus ROI fiber tracts. Overall, individuals with APSS demonstrated white matter microstructural abnormalities, especially in the OrG_A13-NAC fiber tracts. These alterations may contribute to our understanding on the neuropathology of APSS.https://doi.org/10.1038/s41537-025-00635-9
spellingShingle Zhenzhu Chen
Qijing Bo
Lei Zhao
Yushen Ding
Yimeng Wang
Qitong Jiang
Feng Li
Yuan Zhou
Chuanyue Wang
White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
Schizophrenia
title White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
title_full White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
title_fullStr White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
title_full_unstemmed White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
title_short White matter abnormalities of the frontal–striatal–thalamic circuit in individuals with attenuated positive symptom syndromes: a probabilistic tractography study
title_sort white matter abnormalities of the frontal striatal thalamic circuit in individuals with attenuated positive symptom syndromes a probabilistic tractography study
url https://doi.org/10.1038/s41537-025-00635-9
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