The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues

Rationale: Prepulse inhibition (PPI) of the startle reflex is a powerful tool for investigating sensorimotor gating in both animals and humans. Evidence of impaired PPI in patients with schizophrenia suggests that PPI performance might serve as a promising model to investigate the neurobiological mechanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Recent clinical studies suggest that neuroleptic medication is capable of improving deficient PPI performance in schizophrenia patients as well. Objectives: The present paper reviews the published data on PPI performance in schizophrenia patients, focussing on medication effects. Using a modified meta-analytic approach, the consistency of PPI deficits in schizophrenia patients across studies is explored. In particular, methodological issues of defining PPI deficits and assessing PPI improvements are considered. Method: Literature search produced 12 original studies that investigated PPI performance in schizophrenia patients using comparable experimental conditions. Percentage change scores were calculated to compare the actual amount of PPI observed in schizophrenia patients and healthy controls across studies. Results: Results revealed that the amount of PPI in medicated schizophrenia patients was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lead intervals. Moreover, medicated patients showed around 20% less PPI than healthy controls. Whether these group differences were statistically significant depended on the composition of the control group that showed large variability across studies. Conclusions: To delineate the effects of neuroleptic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical research should take advantage of longitudinal designs to disentangle state-dependent medication effects from more stable, trait-linked factors that contribute to PPI deficits in schizophrenia.