ABSTRACT
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.
Subject(s)
Affect/drug effects , Antimetabolites/pharmacology , Antipsychotic Agents/therapeutic use , Cognition Disorders/diagnosis , Cycloserine/pharmacology , Schizophrenia/drug therapy , Antimetabolites/administration & dosage , Antipsychotic Agents/blood , Cycloserine/administration & dosage , Diagnostic and Statistical Manual of Mental Disorders , Double-Blind Method , Drug Administration Schedule , Glycine/metabolism , Humans , Male , Middle Aged , Neuropsychological Tests , Receptors, N-Methyl-D-Aspartate/drug effects , Schizophrenia/diagnosis , Severity of Illness IndexABSTRACT
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.