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Updated: May 5, 2026

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Decreased resting-state interhemispheric functional connectivity in unaffected siblings of schizophrenia patients
Wenbin Guo1, Jiajing Jiang1, Changqing Xiao1
1Mental Health Center, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
Background:
Neuroimaging studies in unaffected siblings of schizophrenia patients can provide clues to the pathophysiology for the development of schizophrenia. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in siblings, although the dysconnectivity hypothesis is prevailing in schizophrenia for years. In the present study, we used a newly validated voxel-mirrored homotopic connectivity (VMHC) method to identify whether aberrant interhemispheric FC was present in unaffected siblings at increased risk of developing schizophrenia at rest.
Methods:
Forty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). Automated VMHC was used to analyze the data.
Results:
The sibling group had lower VMHC than the control group in the angular gyrus (AG) and the lingual gyrus/cerebellum lobule VI. No region exhibited higher VMHC in the sibling group than in the control group. There was no significant sex difference of the VMHC values between male siblings and female siblings or between male controls and female controls, although evidence has been accumulated that size and shape of the corpus callosum, and functional homotopy differ between men and women.
Conclusions:
Our results first suggest that interhemispheric resting-state FC of VMHC is disrupted in unaffected siblings of schizophrenia patients, and add a new clue of abnormal interhemispheric resting-state FC to the pathophysiology for the development of schizophrenia.
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