Psychotherapy for adolescents and young adults at high risk for psychosis: a systematic review.

AIM: Unlike medication treatment, which may confer an unfavourable risk-benefit ratio, psychosocial intervention has been an emerging target of recent randomized controlled trials (RCTs) assessing its efficacy in delaying or preventing the onset of psychosis in individuals identified at 'clinical high risk'. Literature comparing qualitative differences in these psychotherapeutic interventions is scarce. The aim of the current study was to conduct a PRISMA systematic review evaluating the efficacy of psychotherapeutic interventions in reducing the rates of conversion to psychosis in clinical high-risk individuals. METHODS: RCTs were identified in PubMed, Medline and PsycINFO databases up to 30 November 2013. Six studies (comprising 800 participants) met review inclusion criteria. Three investigators performed data extraction independently by using a pre-structured selection form, and conducted risk of bias assessment employing the Cochrane approach. RESULTS: All six studies employed cognitive behaviour therapy as a core element. Three trials achieved a significant effect. The two trials that employed cognitive behaviour therapy enhanced for the specialized needs of clinical high-risk patients maintained significant effects at post-treatment follow up. CONCLUSION: Evidence from recent trials suggest that cognitive behaviour therapy may be beneficial in delaying or preventing onset of psychosis in clinical high-risk individuals, although effect sizes to date appear small. Further research is needed in larger samples to establish whether cognitive behaviour therapy is efficacious, and if additional intervention components can enhance established psychotherapies.

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.

Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys.

RATIONALE: Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating, which occurs across species and is deficient in severe neuropsychiatric disorders such as schizophrenia. In monkeys, as in rodents, phencyclidine (PCP) induces schizophrenia-like deficits in PPI. In rodents, in general, typical antipsychotics (e.g. haloperidol) reverse PPI deficits induced by dopamine (DA) agonists (e.g. apomorphine), but not those induced by N-methyl- d-aspartate (NMDA) receptor antagonists [e.g. phencyclidine (PCP)], whereas atypical antipsychotics (e.g. clozapine) reverse PPI deficits induced by DA agonists and NMDA antagonists. However, some discrepancies exist with some compounds and strains of rodents. OBJECTIVES: This study investigated whether a typical (haloperidol, 0.035 mg/kg) and an atypical (clozapine, 2.5 mg/kg) antipsychotic could be distinguished in their ability to reverse PCP-induced deficits in PPI in eight monkeys ( Cebus apella). METHODS: First, haloperidol dose was determined by its ability to attenuate apomorphine-induced deficits in PPI. Then, haloperidol and clozapine were tested in eight monkeys with PCP-induced deficits of PPI. Experimental parameters were similar to standard human PPI procedures, with 115 dB white noise startle pulses, either alone or preceded by 120 ms with a prepulse 16 dB above the 70 dB background noise. RESULTS: Clozapine reversed PCP-induced PPI deficits. In contrast, haloperidol did not significantly attenuate PCP-induced PPI deficits even at doses that significantly attenuated apomorphine effects. CONCLUSIONS: In this primate model, clozapine was distinguishable from haloperidol by its ability to attenuate PCP-induced deficits in PPI. The results provide further evidence that PPI in nonhuman primates may provide an important animal model for the development of novel anti-schizophrenia medications.