Dr. Kéri Replies

To the Editor: We thank Dr. Lang for her insightful comments. She raises the possibility that second-generation antipsychotics, such as clozapine and olanzapine, may normalize P50 suppression via a specific activating effect on the AKT/glycogen synthase kinase-3β messenger system. The main purpose of our study was to investigate the relationship between P50 suppression and AKT-phosphorylation in never-medicated patients with schizophrenia in order to exclude the potential confounding effect of medications. Our study was not designed to investigate the specific effect of different antipsychotics. The most convincing evidence for a differential effect of second- versus first-generation antipsychotics on P50 suppression and AKT-phosphorylation would come from randomized controlled trials. However, it must be mentioned that we previously observed decreased neuregulin 1-induced AKT-phosphorylation in patients with schizophrenia receiving second-generation antipsychotics (1), suggesting that these drugs do not completely normalize the AKT/glycogen synthase kinase-3β pathway. Further studies are warranted to clarify this issue with the parallel assessment of sensory endophenotypes and molecular mechanisms.