Deficient inhibitory cortical networks in antipsychotic-naive subjects at risk of developing first-episode psychosis and first-episode schizophrenia patients: A cross-sectional study

摘要

Background: Impaired cortical inhibition is a well-established finding in schizophrenia patients and has been linked to dysfunctional gamma-aminobutyric acid (GABA)ergic transmission. However, there have been no previous studies investigating cortical excitability with particular regard to intracortical inhibitory networks in antipsychotic-naive subjects at risk of developing first-episode psychosis. Methods: A total of 18 subjects at risk, 18 first-episode schizophrenia patients, and 18 healthy control subjects were included in this study. Transcranial magnetic stimulation over the left primary motor cortex was used to determine short-latency intracortical inhibition, intracortical facilitation, and the contralateral silent period (CSP). Short-latency intracortical inhibition can be considered as a parameter of GABA type A (GABA A)-mediated inhibition and it has been proposed that CSP can test GABA type B (GABA B)-mediated inhibitory intracortical networks. Results: Subjects at risk and first-episode patients showed a reduced short-latency intracortical inhibition compared with healthy control subjects, suggesting reduced GABA A-mediated inhibition. First-episode patients had a prolonged CSP duration compared with the other two groups, implying a GABA B imbalance only in patients with full-blown psychosis. Analyses did not reveal group differences for intracortical facilitation. Conclusions: These results indicate specific alterations in inhibitory cortical networks in subjects at risk and in first-episode patients. It appears that there is already a cortical inhibitory deficit in at-risk individuals. These results suggest a possible GABA A dysfunction early in the disease course, whereas alterations in GABA B functionality seem to occur later in the disease's progression. Future longitudinal studies will be needed to clarify this inhibitory deficit and its relation to the transition to psychosis.