Alteration in resting state brain connectivity in subjects with high genetic risk of psychosis

Abstract

Objective: Resting state functional connectivity is a relatively novel functional magnetic resonance imaging (fMRI) approach that analyzes the temporal correlation of blood oxygen leveldependent signal fluctuations in different brain areas that is not attributable to specific inputs and outputs. It represents neuronal activity that is intrinsically generated by the brain. Several fMRI studies of schizophrenia have revealed the default mode network abnormalities during resting state. Midline default network areas have been implicated in self-referential and social cognitions. Cognitive and behavioral deficits in patients with schizophrenia and subjects with high genetic risk of psychosis might be related to dysfunctions of these networks. However, no study to date has investigated resting state default mode network in subjects with high genetic risk of psychosis. The aim of the current study was to examine whether functional connectivity in default mode network was altered in subject with high genetic risk during resting state. It was hypothesized that the subjects with high genetic risk would show abnormal spatial and/or temporal patterns in default mode network. Method: Sixteen subjects with high genetic risk of psychosis who had never had a psychotic disorder but who had at least two relatives with schizophrenia and 16 age-, and sex-matched healthy controls were included in this study. All subjects were scanned for 4.68 minutes (120 volumes) using fMRI during resting state. A posterior cingulate cortex seed region connectivity analysis was used to identify the default mode network and this resting state default mode functional connectivity was compared for both groups. Correlations between temporal connectivity with the posterior cingulate cortex seed region in each regions of interest and clinical measures were also assessed. Results: Both groups showed similar default mode network in regions previous associated with this network. The areas within the default mode network included the posterior cingulate cortex, medial prefrontal cortex, inferior parietal cortex, and lateral temporal region. However, this network in subjects with high genetic risk was much more loosely connected, showing reduced correlation between the posterior cingulate cortex and the prefrontal cortex compared with healthy controls. In addition, the connectivity between the posterior cingulate cortex seed region and the prefrontal cortices in high genetic risk group correlated with total and general scores of Positive and Negative Syndrome Scale. Conclusions: The results of the current study demonstrated significant abnormalities in the default mode network in subjects with high genetic risk. Alterations in the connectivity within the default mode network in the prefrontal cortex might be associated with disturbance of self-perception and social functions. Neurodevelopmental and anatomical alterations of cortical midline structures might also underlie altered intrinsic default network in subjects with high genetic risk. Further research to clarify the functional connectivity change after longitudinal follow-up should increase our understanding of the pathophysiology of psychosis.