The relationship between acoustic startle response measures and cognitive functions in Japanese patients with schizophrenia.

Recently, schizophrenia endophenotypes have been actively investigated to better understand the pathophysiology of schizophrenia. Past studies have shown that cognitive functions, including working memory and executive function, correlate with acoustic startle responses, such as prepulse inhibition (PPI), in patients with schizophrenia. The aim of this study was to investigate the relationship between cognitive functions and acoustic startle response in Japanese patients with schizophrenia. In 100 patients with schizophrenia, we evaluated cognitive function, using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J), and acoustic startle responses, including acoustic startle reflex, habituation, and PPI (three different intensities: 82, 86, and 90 dB SPL, equivalent to signal-to-noise ratios of +12, +16, and +20 dB, respectively). Using multiple regression analysis, we examined the relationship between acoustic startle responses and BACS-J primary measures or composite score. Level of attention was associated with magnitude of habituation in schizophrenia (P = 0.0009, ß = -0.357). None of the other domains of cognitive function were significantly associated with any measure of acoustic startle response. This included attention regarding ASR (P = 0.513), PPI (P = 0.521-0.842), verbal memory (P = 0.423-0.981), working memory (P = 0.312-0.966), motor speed (P = 0.323-0.955), verbal fluency (P = 0.125-0.920), executive function (P = 0.118-0.470), and the BACS-J composite score (P = 0.230-0.912). In this first investigation of the relationship between cognitive functions and acoustic startle responses in Japanese patients with schizophrenia, attentional deficits correlated highly with the level of habituation. However, a replication study using other population samples is required to further investigate this relationship.

Effect of aripiprazole, risperidone, and olanzapine on the acoustic startle response in Japanese chronic schizophrenia.

BACKGROUND: Studies have also shown that differences in the kind of the antipsychotics influenced disruption of the sensorimotor gating system, including prepulse inhibition (PPI), acoustic startle reflex (ASR), and habituation (HAB). We investigated the influence on startle response in chronic schizophrenia in 20 patients with schizophrenia taking risperidone, 21 patients with schizophrenia taking olanzapine, and 20 patients with schizophrenia taking aripiprazole. METHOD: The patients who participated in this study were on maintenance therapy with only one antipsychotic drug for 4 months. We performed the test for the association between all PPI measures (ASR, HAB, and PPI at prepulse sound pressure intensities of 82, 86, and 90 dB) and each the risperidene, olanzapine, and aripiprazole groups, with analysis of covariance (ANCOVA; using age, duration of illness, and daily dose of the antipsychotic as covariates). Also, when significant difference was detected in ANCOVA, the differences of PPI measures between every pairs of two drug groups were tested as a post hoc analysis with the use of t test and Bonferroni's correction of multiple tests. RESULT: We found that PPI90 showed significant differences with ANCOVA among patients with schizophrenia taking each of the antipsychotics. When we performed a post hoc analysis for PPI90, the value was higher in the aripiprazole group than in the olanzapine group and higher in the risperidone group than in the olanzapine group. CONCLUSION: Aripiprazole and risperidone may improve PPI90. ASR, HAB, PPI82, and PPI86 were no different among the Japanese schizophrenic patient groups with different antipsychotics.

Prepulse inhibition of the startle response with chronic schizophrenia: a replication study.

Prepulse inhibition (PPI) deficit, the acoustic startle reflex (ASR) and habituation (HAB) impairment are considered to be endophenotypes for schizophrenia. The recent two studies have reported that a PPI deficit was detected in Japanese schizophrenic patients. We replicated that study using larger samples (115 schizophrenic patients and 111 normal controls) than the original study and a method same as original study. A startle response monitoring system was used to deliver acoustic startle stimuli, and to record and score the electromyographic activity of the orbicularis oculi muscle. We evaluated the startle measures of mean magnitude of ASR, HAB, and PPI at prepulse sound pressure intensities of 82dB (PPI82), 86dB (PPI86), and 90dB (PPI90). ASR was significantly different between schizophrenic patients and controls. HAB and all PPI session data from schizophrenic patients were significantly lower than in controls. In addition, we detected significant differences for ASR, HAB and each PPI (82, 86 and 90dB) between schizophrenic patients and controls with the use of multiple regression analysis. The gender and smoking state were not correlated with ASR, HAB or any PPI in multiple regression analysis. In conclusion, we were able to replicate the finding of HAB impairment and PPI deficit in chronic Japanese schizophrenic patients.