Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia.

Inhibition of the acoustic startle response by a smaller preliminary nonstartling stimulus is termed prepulse inhibition (PPI). Schizophrenia patients have impairments in PPI that may not fully normalize even when they are clinically stable on medication, particularly typical antipsychotics. There is evidence that more severe symptoms are associated with more severe PPI abnormalities, but the effect of antipsychotics on this relationship is not clear. Seventy-three male schizophrenia patients underwent acoustic startle and PPI testing. Symptom ratings were performed using the Brief Psychiatric Rating Scale (BPRS) and its subscales. Fifty-two subjects were treated with antipsychotic medication at time of testing; 21 were unmedicated. For all subjects, PPI was negatively correlated with the BPRS psychological discomfort subscale but not with BPRS total symptoms, BPRS positive symptoms or BPRS negative symptoms. For medicated subjects analyzed separately, there were no correlations with BPRS total scores or any subscales. For the unmedicated subjects analyzed separately, there were significant correlations of lower PPI with greater severity of BPRS total symptoms, positive symptoms and the psychological discomfort subscale. These data indicate that more severe symptoms are associated with lower PPI, but that medication status is an important factor in the relationship between symptom severity and sensorimotor gating.

The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers.

RATIONALE: N-methyl-D: -aspartate (NMDA) glutamate receptor antagonists have been reported to induce schizophrenia-like symptoms in humans, including memory impairments. Although the NMDA receptor has been shown to impair memory acquisition by disrupting long-term potentiation (LTP), limited research has been done on studying the effects of NMDA antagonists on the post-LTP cascade of events implicated in consolidation as measured by administering the drug after the initial learning experience. OBJECTIVE: The purpose of this experiment was to examine the effect of ketamine on mental status and to identify NMDA antagonist-induced memory deficits by comparing the recall performance of items presented both immediately before and during ketamine infusion. METHODS: Thirteen normal controls received a 60-min infusion of ketamine in a randomized double-blind, cross-over design. Mental status was evaluated with the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale. The first 12-item word list was presented immediately before infusion, and two lists were subsequently presented during the infusion. Verbal memory performance was assessed by measuring the delayed cued recall of each list 30 min after its presentation. RESULTS: At the beginning, subjects experienced perceptual and reality distortion symptoms, followed later by mild subjective effects. Ketamine significantly reduced the delayed recall of words presented immediately before, but not during, drug infusion. Ketamine-induced decrements in verbal recall correlated significantly with plasma ketamine levels. CONCLUSION: This study characterizes the behavioral effects associated with ketamine and suggests that ketamine decreases verbal memory performance by interfering with early consolidation processes.

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.

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.