Reduced prefrontal functional connectivity in the default mode network is related to greater psychopathology in subjects with high genetic loading for schizophrenia

Objective: Neuroimaging studies in subjects at genetic high risk (GHR) of schizophrenia can provide clues to the causes for the development of schizophrenia. Little is known about genetic influence on functional connectivity status, although studies on schizophrenia have reported an abnormal default mode network (DMN). We sought to identify putative genetic vulnerability markers by examining whether aberrant DMN connectivity was present in GHR subjects with high genetic loading. Method: Sixteen GHR subjects who had at least two relatives with schizophrenia and 16 age- and sex-matched controls were included and scanned using resting-state functional magnetic resonance imaging. A posterior cingulate cortex (PCC) seed region connectivity analysis was used to identify the DMN. Correlations between severity of psychopathology, level of genetic loading and DMN connectivity were calculated. Results: The DMN network in GHR subjects showed reduced functional connectivity in the prefrontal areas, PCC, and precuneus. In addition, this reduced connectivity in the prefrontal cortices correlated with total and general scores on the Positive and Negative Syndrome Scale. GHR subjects having two first-degree relatives with schizophrenia showed a trend toward greater reduction in DMN connectivity in the precuneus and anterior cingulate cortex. Conclusion: This study suggests significant abnormalities in the DMN of subjects at GHR of schizophrenia. Alterations of DMN connectivity in the prefrontal cortex may reflect psychopathologies such as an inability to allocate resources properly between internal thoughts and external stimuli. Dysfunction of the anterior cingulate cortex and precuneus might be related to genetic risk for schizophrenia.