Prolonged cortical silent period among drug-naive subjects at ultra-high risk of psychosis.

BACKGROUND Deficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission have been associated with pathophysiological mechanisms underlying schizophrenia. However, little is known about whether these deficits occur before or after the onset of psychosis. METHOD We recruited 16 drug-naive subjects at ultra-high risk of psychosis (UHR), 17 schizophrenia patients and 28 healthy controls. Cortical inhibition was determined using transcranial magnetic stimulation (TMS) over the left primary motor cortex. TMS markers such as short-interval cortical inhibition (SICI), cortical silent period (CSP) and intracortical facilitation (ICF) were obtained from each subject. While SICI can reflect GABA type A (GABAA) mediated inhibition, CSP is thought to indicate GABA type B (GABAB) mediated inhibitory circuits. RESULTS As compared with healthy controls, UHR subjects showed a prolonged CSP with no change in SICI, whereas schizophrenia patients demonstrated both a prolonged CSP and a reduced SICI. No group differences were found for ICF. CSP in schizophrenia patients also had a positive correlation with positive symptom score of the positive and negative symptom scale (PANSS). CONCLUSIONS Cortical inhibitory deficits among UHR subjects were relatively limited compared to those among schizophrenia patients. Alterations might occur in some subgroup of GABA-mediated neurotransmitter systems before the onset of psychosis, while alterations in both GABAA and GABAB networks might contribute to full-blown psychosis.