Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.Design 12 month randomised, double blind, placebo controlled trial.Setting Early psychosis outpatient clinics in Hong Kong.Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ 2 =3.20, df=1; P=0.07).Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.Trial registration Clinical trials NCT00334035. INTRODUCTIONPrevention of relapse is an important target in the treatment of schizophrenia and related psychotic conditions.1 In first episode psychosis, more than 80% of patients treated achieve a full response in psychotic symptoms, 2 yet as many as 80% have a relapse within five years.3 Relapse compromises the outcome of psychotic disorders and is associated with substantial risks and costs. 4 With each relapse, the response of symptoms to treatment seems to take approximately 50% longer and is increasingly difficult to reestablish.5 Prevention of relapse is particularly important in the early course of illness, when symptoms and disabilities may be less entrenched. Strategies to improve adherence and minimise early relapses are major focuses in treatment programmes and clinical research.1 For chronic psychotic illness, maintenance antipsychotic drug treatment is efficacious for preventing relapse. The rate of relapse after discontinuation of drug treatment in chronic schizophrenia is approximately 53% compared with 16% for patients maintained on antipsychotic drugs.6 Atypical antipsychotic drugs may have some benefits compared with typical antipsychotics in preventing relapse in chronic illness.7 8 The biological mechanism underlying relaps...

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We propose three novel directions for further psychosis endophenotype research: (1) in addition to such content-independent computational processes, which operate in a similar way regardless of the stimuli, it is important to consider the potential roles of "content-dependent endophenotypes", which operate on different stimuli in consistently different manners. Advances in cognitive studies suggest there may be evolutionarily important aspects of cognition which are content-dependent. We propose that both content-independent and content-dependent processes should be addressed in psychosis research. (2) In line with the emphasis on content, close attention should be paid to the study of "psychopathological endophenotypes" in addition to cognitive endophenotypes. (3) "Neurocomputational endophenotypes" may be defined by parsing cognitive processes into "subsystems" with specific computational processing algorithms and considering key computational parameters suggested from these models. These potential "neurocomputational endophenotypes" (such as neuronal noise, synaptic learning algorithms) are potentially intermediate variables located between the levels of cognition and neurobiology.

Introduction: Neurological soft signs (NSS) are suggested as a candidate endophenotype for schizophrenia. This article aims to review relevant literature and discuss the role of NSS in understanding schizophrenia. Methods: This is an update on a review article published in 2003. Articles from 2003 onwards were specifically reviewed and discussed with relevance to the role of NSS as endophenotype for schizophrenia. Results: Consistent data suggest an excess of NSS in schizophrenic patients. NSS appear to be related to schizophrenic symptoms, in particular negative symptoms and disorganisation. Information on NSS and demographic correlates is scarce, and the confounding effects between age, education and intelligence on NSS constitute an important gap in current knowledge. Longitudinal data suggest NSS as both a trait and state variable in the course of disease. NSS are not specific with regard to diagnosis, although there are claims that individual sub-components may be more specific. The weight of evidence raises question on the specificity of NSS for schizophrenia. Conclusions: The usefulness and feasibility of NSS as a specific endophenotype target for schizophrenia is unclear. However, NSS remain an important feature and symptom correlate of schizophrenia. Future research should focus on delineating the effects of NSS from those of confounding demographic variables, and the stability of NSS over the course of illness to elucidate its role in schizophrenia. Key words: Diagnostic specificity, Neurological examination abnormalities, Psychotic symptoms, Review, Trait