Enhanced Global-Brain Functional Connectivity in the Left Superior Frontal Gyrus as a Possible Endophenotype for Schizophrenia.

Yudan Ding,Jingping Zhao,Feng Liu,Wenbin Guo,Zhikun Zhang,Qinji Su,Xiaoxiao Shan,Pan Pan,Yangpan Ou,Jindong Chen

doi:10.3389/fnins.2019.00145

Abstract

The notion of dysconnectivity in schizophrenia has been put forward for many years and results in substantial attempts to explore altered functional connectivity (FC) within different networks with inconsistent results. Clinical, demographical, and methodological heterogeneity may contribute to the inconsistency. Forty-four patients with first-episode, drug-naive schizophrenia, 42 unaffected siblings of schizophrenia patients and 44 healthy controls took part in this study. Global-brain FC (GFC) was employed to analyze the imaging data. Compared with healthy controls, patients with schizophrenia and unaffected siblings shared enhanced GFC in the left superior frontal gyrus (SFG). In addition, patients had increased GFC mainly in the thalamo-cortical network, including the bilateral thalamus, bilateral posterior cingulate cortex (PCC)/precuneus, left superior medial prefrontal cortex (MPFC), right angular gyrus, and right SFG/middle frontal gyrus and decreased GFC in the left ITG/cerebellum Crus I. No other altered GFC values were observed in the siblings group relative to the control group. Further ROC analysis showed that increased GFC in the left SFG could separate the patients or the siblings from the controls with acceptable sensitivities. Our findings suggest that increased GFC in the left SFG may serve as a potential endophenotype for schizophrenia.

Highlights

Characterized by disturbances of perception (Yoon et al, 2008), cognition (Barch and Csernansky, 2007), emotion (Holt et al, 2011), and thought (Corlett et al, 2007), schizophrenia is a devastating and complex mental disorder, affecting adults as well as adolescence with highly heterogeneous and multifaceted clinical syndromes instead of a single disease entity (Yu et al, 2017)
We aimed to explore global-brain functional connectivity (FC) (GFC) differences by comparing a group of first-episode, drug-naive patients with schizophrenia and unaffected siblings with healthy controls employing the voxel-wise model-free Global-brain FC (GFC) method, which had been described in details in our previous study (Cui et al, 2018)
The diagnosis of schizophrenia was made by two research psychiatrists (W.G. and Z.Z.) according to the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSMIV) criteria, patient edition, whereas non-patient version was used for unaffected siblings and healthy controls to rule out any psychiatric conditions

Summary

Introduction

Characterized by disturbances of perception (Yoon et al, 2008), cognition (Barch and Csernansky, 2007), emotion (Holt et al, 2011), and thought (Corlett et al, 2007), schizophrenia is a devastating and complex mental disorder, affecting adults as well as adolescence with highly heterogeneous and multifaceted clinical syndromes instead of a single disease entity (Yu et al, 2017). Unaffected siblings of patients with schizophrenia, a subgroup of high risk subjects with approximately 50% of genetic burden (Pergola et al, 2017), have about a 10-fold increased risk to develop schizophrenia than general population (Chang et al, 2002). Similar brain abnormalities shared by patients with schizophrenia and unaffected siblings can be regarded as potential endophenotypes for schizophrenia. Endophenotypes are some heritable and characteristic changes certainly present in patients but are possible to appear in unaffected relatives. They segregate with the disease within families and can be biochemical, neuroanatomical, cognitive, endocrine, or neurophysiological parameters (Gottesman and Gould, 2003; Bertolino and Blasi, 2009)

Objectives

Methods

Results

Conclusion