Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia.

RATIONALE: The acoustic startle response is inhibited when the startling stimulus is preceded by a weaker non-startling acoustic stimulus. This phenomenon, termed prepulse inhibition of acoustic startle (PPI), is impaired in schizophrenics compared to normal controls. To date, there is conflicting evidence regarding whether PPI impairments improve with antipsychotic treatment. OBJECTIVES: To examine the effect of medication status on PPI in schizophrenic subjects. METHODS: First, we performed acoustic startle testing on 16 schizophrenic subjects when they were acutely decompensated off medication and later after they were stabilized on antipsychotic treatment. Second, in a between-group design, we tested 21 schizophrenic subjects off medication, 16 subjects on atypical neuroleptics, and 27 subjects on typical neuroleptics. RESULTS: In both the test-retest study and the between-group study, ANOVAs revealed no significant changes in startle to pulse alone stimuli, habituation of startle to pulse alone stimuli, PPI, latency to response onset, or latency to response peak between the treatment conditions. CONCLUSIONS: Our results do not support the hypothesis that impaired sensorimotor gating in schizophrenia improves with antipsychotic treatment. Rather, impaired gating persists despite symptomatic improvement on medication.

Effects of D-cycloserine on negative symptoms in schizophrenia.

INTRODUCTION: The negative and cognitive symptoms of schizophrenia are poorly responsive to neuroleptic treatment. Glutamatergic dysfunction may mediate some of these symptoms. Low dose D-cycloserine (DCS) is a partial agonist at the glycine site of the NMDA-associated receptor complex, noncompetitively enhancing NMDA neurotransmission. Prior studies suggest a beneficial effect of DCS on negative symptoms and cognition. This treatment trial was initiated to confirm and extend these findings. METHODS: Twenty-two male schizophrenic subjects displaying prominent negative symptoms who were stabilized on typical neuroleptics completed the study. A randomized double-blind parallel group design was used to compare the effects of 50 mg p.o. QD of DCS to placebo over 4 weeks. The two subject groups did not differ significantly in age, age of onset of illness or time on current neuroleptic treatment. Symptoms were rated by means of the SANS, BPRS and Abrams and Taylor rating scale. Cognition was assessed with the Sternberg Memory Test and the Continuous Performance Test. RESULTS: Both medication groups improved over the 4 weeks of treatment. However, there were no significant differences between the DCS and placebo group on any symptom rating. DCS effects on cognition did not differ from placebo. DISCUSSION: This study did not detect improvement in negative symptoms or cognitive performance with DCS treatment that has been found in some prior studies. This negative finding may be attributed to small sample size, relatively short duration of treatment and the overall modest effect of DCS. Future studies of DCS should be adequately powered to detect a small to medium effect size and should provide for a longer treatment phase than was used in this study in order to avoid a type II error.

Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol.

Studies of the acoustic startle response and of its inhibition by the presentation of a non-startling preliminary stimulus (prepulse inhibition, PPI) have revealed deficits in PPI in schizophrenic subjects compared to healthy controls. Animal studies indicate that atypical antipsychotics improve PPI deficits induced by NMDA antagonists more consistently than typical antipsychotics. The effect of medication status on PPI in schizophrenia is unresolved in the literature. In the current study the effects on PPI of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol were compared to the unmedicated state in subjects with schizophrenia. In a between-group design, 11 schizophrenic subjects on olanzapine, 16 subjects on haloperidol, and 14 subjects who were on no medication received acoustic startle testing with PPI determination. ANOVAs revealed no significant differences in startle to pulse alone stimuli, habituation of startle, or PPI between the olanzapine, haloperidol and unmedicated groups. These 41 subjects with schizophrenia were compared to a group of 21 historical healthy controls and found to have reduced PPI. These data do not indicate a preferential effect of olanzapine compared to haloperidol on sensorimotor gating in schizophrenia. The results are consistent with the hypothesis that PPI impairments are relatively stable across treatment conditions.

Menstrual cycle phase effects on prepulse inhibition of acoustic startle.

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating.