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

作者：Hasan Alkomiet; Wobrock Thomas^*; Grefkes Christian; Labusga Marcin; Levold Katrin; Schneider Axmann Thomas; Falkai Peter; Mueller Hendrik; Klosterkoetter Joachim; Bechdolf Andreas

来源：Biological Psychiatry, 2012, 72(9): 744-751.

DOI：10.1016/j.biopsych.2012.03.005

• Cortical inhibition
• first-episode schizophrenia
• GABA
• prodrome
• schizophrenia
• transcranial magnetic stimulation

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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%26apos;s progression. Future longitudinal studies will be needed to clarify this inhibitory deficit and its relation to the transition to psychosis.

• 出版日期2012-11-1