Family-based case-control study of homotopic connectivity in first-episode, drug-naive schizophrenia at rest

Wenbin Guo,Lehua Li,Zhikun Zhang,Jingping Zhao,Jindong Chen,Renrong Wu,Feng Liu

doi:10.1038/srep43312

Abstract

Family-based case-control design is rarely used but powerful to reduce the confounding effects of environmental factors on schizophrenia. Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 family-based controls (FBC), and 40 healthy controls (HC) underwent resting-state functional MRI. Voxel-mirrored homotopic connectivity (VMHC), receiver operating characteristic curve (ROC), and support vector machine (SVM) were used to process the data. Compared with the FBC, the patients showed lower VMHC in the precuneus, fusiform gyrus/cerebellum lobule VI, and lingual gyrus/cerebellum lobule VI. The patients exhibited lower VMHC in the precuneus relative to the HC. ROC analysis exhibited that the VMHC values in these brain regions might not be ideal biomarkers to distinguish the patients from the FBC/HC. However, SVM analysis indicated that a combination of VMHC values in the precuneus and lingual gyrus/cerebellum lobule VI might be used as a potential biomarker to distinguish the patients from the FBC with a sensitivity of 96.43%, a specificity of 89.29%, and an accuracy of 92.86%. Results suggested that patients with schizophrenia have decreased homotopic connectivity in the motor and low level sensory processing regions. Neuroimaging studies can adopt family-based case-control design as a viable option to reduce the confounding effects of environmental factors on schizophrenia.

Highlights

Most of the above-mentioned studies used a traditional case-control design
Using a family-based case-control design, the present study reveals decreased homotopic connectivity in the motor and low level sensory processing regions of first-episode, drug-naive patients with schizophrenia
No correlations can be observed between decreased VMHC and clinical symptoms (PANSS scores)

Summary

Introduction

Most of the above-mentioned studies used a traditional case-control design. Few studies employed a family-based case-control design, which is a powerful tool to limit the confounding effects of environmental risk factors on gene-related diseases, such as schizophrenia. We applied a family-based case-control design to examine functional homotopy abnormalities in first-episode, drug-naive patients with schizophrenia. A positive correlation was observed between the abnormal VMHC values across all three deficit clusters in the patients and the FBC (r = 0.394, p = 0.038, Fig. 2).

Results

Conclusion