Sex differences in functional connectivity in first-episode and chronic schizophrenia patients

Objective: There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia. Method: Forty patients with chronic schizophrenia (20 women and 20 men) and 24 patients with first-episode schizophrenia (12 women and 12 men) and their respective matched comparison groups completed a conventional auditory odd-ball task. Phase synchronous gamma (40 Hz) activity was extracted from EEG recording during the task and time-locked to the oddball (target) stimuli. Results: Chronic schizophrenia subjects showed a reduction in global functional connectivity (lower gamma phase synchrony) relative to their matched healthy subjects. Unexpectedly, this reduction was most apparent in female patients. By contrast, while first-episode patients showed a general reduction in the speed of frontal connectivity, the speed of global connectivity was relatively faster in female patients. Conclusions: This is the first study to investigate sex differences in schizophrenia that used the functional connectivity measure of gamma phase synchrony. The results suggest that in female patients with schizophrenia, additional breakdowns in brain network connectivity may develop with illness chronicity.