Psychosis Incident Cohort Outcome Study (PICOS). A multisite study of clinical, social and biological characteristics, patterns of care and predictors of outcome in first-episode psychosis. Background, methodology and overview of the patient sample.

AIMS: This paper aims at providing an overview of the background, design and initial findings of Psychosis Incident Cohort Outcome Study (PICOS). METHODS: PICOS is a large multi-site population-based study on first-episode psychosis (FEP) patients attending public mental health services in the Veneto region (Italy) over a 3-year period. PICOS has a naturalistic longitudinal design and it includes three different modules addressing, respectively, clinical and social variables, genetics and brain imaging. Its primary aims are to characterize FEP patients in terms of clinical, psychological and social presentation, and to investigate the relative weight of clinical, environmental and biological factors (i.e. genetics and brain structure/functioning) in predicting the outcome of FEP. RESULTS: An in-depth description of the research methodology is given first. Details on recruitment phase and baseline and follow-up evaluations are then provided. Initial findings relating to patients' baseline assessments are also presented. Future planned analyses are outlined. CONCLUSIONS: Both strengths and limitations of PICOS are discussed in the light of issues not addressed in the current literature on FEP. This study aims at making a substantial contribution to research on FEP patients. It is hoped that the research strategies adopted in PICOS will enhance the convergence of methodologies in ongoing and future studies on FEP.

The influence of gender on clinical and social characteristics of patients at psychosis onset: A report from the Psychosis Incident Cohort Outcome Study (PICOS).

BACKGROUND. This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females(by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis. METHOD. A large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework ­ a multi-site research project examining incident cases of psychosis in Italy's Veneto region. RESULTS. Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal care givers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.CONCLUSIONS. These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care.

The differential effect of illicit drug use on cognitive function in first-episode psychosis and healthy controls.

OBJECTIVE: Illicit drug use can result in impairment in cognitive function in healthy individuals. Individuals with a psychotic disorder also show a deficit in cognitive function. Drug use may simply contribute to the characteristic cognitive deficit found in psychosis or alternatively result in a 'double deficit'. This study aims to investigate the association between drug use and cognitive function at the first-episode of psychosis and in community-matched controls. METHOD: One hundred and seventy-seven patients at the first episode of psychosis completed a battery of neuropsychological tests. Those that had used drugs in the previous year (n = 80) were compared with those who had not used drugs in the previous year (n = 97). A subsample of the first-episode psychosis patients were compared with community-matched controls (n = 110) according to drug-use status. RESULTS: Patients with a first episode of psychosis who had used drugs performed equally to those who had not used drugs on neuropsychological tests. In contrast, healthy controls who had used drugs in the previous year performed worse on tests of executive function and working memory compared with those controls that had not used drugs. CONCLUSION: There are differential associations of illicit drug misuse with cognitive function for first-episode psychosis patients and healthy controls.

Illicit substance use and its correlates in first episode psychosis.

OBJECTIVE: To determine if substance use (particularly cannabis) is more frequent among first episode psychosis patients and associated with a more problematic clinical presentation. METHOD: All first episode psychosis (FEP) patients presenting to secondary services were recruited from London and Nottingham, over 2 years, in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study broad framework. Clinical and sociodemographic variables were assessed using a set of standardized instruments. A schedule was created to retrospectively collate substance use data from patients, relatives and clinicians. RESULTS: Five hundred and eleven FEP were identified. They used three to five times more substances than general population. Substance use was associated with poorer social adjustment and a more acute mode of onset. Cannabis use did not affect social adjustment, but was associated with a more acute mode of onset. CONCLUSION: Cannabis has a different impact on FEP than other substances. Large epidemiological studies are needed to disentangle cannabis effect.

Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis.

Impairments of cortical cholinergic inputs from the nucleus basalis magnocellularis fundamentally alter information processing and attentional function, thereby advancing the severity of psychopathology in major neuropsychiatric disorders. It was previously shown in adult rats that bilateral 192 IgG saporin-induced selective immunolesioning of the cholinergic neurons in the nucleus basalis produces pronounced and long-lasting deficits in sensorimotor gating measured by prepulse inhibition of the startle reflex. This behavioral paradigm is considered a valid model of sensorimotor gating deficits in the psychotic spectrum and efforts to analyze the significance of the cholinergic basal forebrain in this context are of great interest. In the present study the predictive value of the selective cholinergic immunolesioning model was tested by examining the ability of the cholinesterase inhibitor rivastigmine to restore prepulse inhibition in immunolesioned rats. We report here a pronounced restoring effect of acute (0.75 or 1.5 mg/kg s.c.) as well as repeated (0.75 mg/kg s.c. b.i.d., for 10 days) treatment with rivastigmine in this model of disrupted prepulse inhibition. Intra-nucleus basalis magnocellularis infusions of 192 IgG saporin resulted in extensive loss of basal-cortical cholinergic neurons as shown by the marked decrease in basal telencephalic choline acetyltransferase immunopositive neurons and cortical choline acetyltransferase activity. In this condition, rivastigmine was found to significantly increase cortical acetylcholine extracellular levels in lesioned animals measured by in vivo microdialysis. Taken together, our results strengthen the proposal that the nucleus basalis represents a critical station of the startle gating circuitry. In addition, our findings strongly indicate that even after dramatic decrease of cholinergic neurons, inhibition of acetylcholinesterase restores the cholinergic synaptic function to a point approaching normalization of experimentally induced psychopathology.

Combined alpha 2-adrenergic/D2 dopamine receptor blockade fails to reproduce the ability of clozapine to reverse phencyclidine-induced deficits in prepulse inhibition of startle.

RATIONALE: The combination of idazoxan, a specific alpha(2)-adrenoceptor antagonist with raclopride, a selective D(2)/D(3) receptor antagonist, has been recently proposed to produce an "atypical" antipsychotic profile comparable to that of clozapine, based on an animal study which analysed dopamine efflux in the medial prefrontal cortex and the preclinical test of conditioned avoidance response (CAR) for evaluation of antipsychotic potential. Accordingly, the combination of a "typical" antipsychotic with idazoxan has been proposed as an augmentation strategy in treatment-resistant schizophrenia, although its therapeutic potential remains difficult to predict. OBJECTIVES: Given the momentum stimulated by these reports, the present study investigated whether the combination of idazoxan with raclopride is indeed sufficient to mimic the ability of clozapine to reverse prepulse inhibition (PPI) deficits in rats, a behavioral paradigm that models PPI deficits observed in the schizophrenia spectrum, and currently the only test which reliably appears to distinguish between "typical" antipsychotics and compounds with "atypical" antipsychotic potential. METHODS: The effects of the combination idazoxan/raclopride were examined in two PPI paradigms: 1) phencyclidine (PCP)-induced disruption of PPI, which has been shown to be preferentially reversed by "atypical" antipsychotics; 2) apomorphine-induced disruption of PPI which can be reversed by either "typical" high-potency D(2) dopamine antagonists or "atypical" antipsychotics. RESULTS: In contrast to clozapine, combining idazoxan with raclopride failed to reverse PCP-induced deficits in PPI. In addition, there was no evidence of an enhancing effect of idazoxan on the blockade of apomorphine-induced disruption of PPI by raclopride. CONCLUSION: The present results challenge the hypothesis that simple alpha(2)/D(2) blockade is sufficient to produce clozapine-like "atypical" antipsychotic activities, and support the consensus that the PPI paradigm represents the most sophisticated behavioral preclinical test for detecting selective "atypical" profile of antipsychotics.