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 to ol for investigating sensorimotor gating in both animals and humans. Eviden ce of impaired PPI in patients with schizophrenia suggests that PPI perform ance might serve as a promising model to investigate the neurobiological me chanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Rec ent clinical studies suggest that neuroleptic medication is capable of impr oving deficient PPI performance in schizophrenia patients as well. Objectiv es: The present paper reviews the published data on PPI performance in schi zophrenia patients, focussing on medication effects. Using a modified meta- analytic approach, the consistency of PPI deficits in schizophrenia patient s across studies is explored. In particular, methodological issues of defin ing PPI deficits and assessing PPI improvements are considered. Method: Lit erature search produced 12 original studies that investigated PPI performan ce in schizophrenia patients using comparable experimental conditions. Perc entage change scores were calculated to compare the actual amount of PPI ob served in schizophrenia patients and healthy controls across studies. Resul ts: Results revealed that the amount of PPI in medicated schizophrenia pati ents was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lea d intervals. Moreover, medicated patients showed around 20% less PPI than h ealthy controls. Whether these group differences were statistically signifi cant depended on the composition of the control group that showed large var iability across studies. Conclusions: To delineate the effects of neurolept ic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical researc h should take advantage of longitudinal designs to disentangle state-depend ent medication effects from more stable, trait-linked factors that contribu te to PPI deficits in schizophrenia.