Deficient Inhibitory Cortical Networks in Antipsychotic-Naive Subjects at Risk of Developing First-Episode Psychosis and First-Episode Schizophrenia Patients: A Cross-Sectional Study

Abstract

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. 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. 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. 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.