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Understanding and improving the outcomes of psychosis remains a major challenge for clinical research. Obstetric complications (OCs) as a risk factor for schizophrenia (SZ) have been investigated as a potential predictor of outcomes in relation to illness severity and poorer treatment outcome, but there are less reports on first episode psychosis (FEP) patients. We test whether OCs, collected in a cohort of FEP patients, can predict illness course and psychopathology severity after 2 years from the onset. Moreover, we explore whether the SZ-polygenic risk score (PRS) would predict the illness course and whether the interaction between OCS and PRS shows a significant effect. A cohort of 264 FEP patients were assessed with standardized instruments. OCs were recorded using the Lewis–Murray scale in interviews with the patients’ mothers: 30% of them reported at least one OC. Patients with at least one OC were more likely to have a non-remitting course of illness compared to those without OCs (35.3% vs. 16.3%, p = 0.014). No association between SZ-PRS and course of illness nor evidence for a gene–environment interaction was found. In our sample, poor short-term outcomes were associated with OCs, while SZ-PRS was not a prognostic indicator of poor outcomes.

Aim Current diagnostic systems, DSM-5 and ICD-10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non-affective psychosis from a dimensional approach. Methods Participants with a first episode psychosis (FEP) were recruited from a cluster-randomized controlled trial (GET-UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. A two-step cluster analysis was performed. Results Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four-cluster solution: delusional-persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative-disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non-affective dimensions. Among non-affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms. Conclusions Symptom dimensions may represent a useful tool for dissecting the indistinct and non-specific psychopathology of FEP in order to better target specific interventions.

To describe pathways to care, duration of untreated psychosis (DUP), and types of interventions provided to first-episode psychosis (FEP) patients by routine Italian mental health services over 5 years since the first service contact. Naturalistic study conducted in Veneto, within the context of the Psychosis Incident Cohort Outcome Study (PICOS). A comprehensive set of measures was used, including schedules designed to collect information on referrals to psychiatric services and on psychological and pharmacological treatments at 1, 2, and 5 years since first service contact. Overall, 397 patients were assessed. Most engaged with services with the help of family members (47.4%) and through emergency routes (60.3%). Those referred by clinicians were more likely to access care in a non-emergency way. Mean DUP was 5.62 months (SD 11.8) and longer DUP was associated with poorer functioning at 2 and 5 years. Interventions provided over 5 years were mainly constituted by antipsychotic medications (95.4% at 1 year; 85.8% at 2 years; 80.6% at 5 years), whereas a lower percentage (69.1% at 1 year; 61.5% at 2 years; 44.9% at 5 years) also received some forms of psychological interventions, mainly consisting of unspecific support sessions. Other structured interventions, such as CBT or family interventions, were seldom provided at each time-point. Mental health services in Veneto seem effective in engaging FEP patients within a short time since illness onset. However, type of care provided does not meet quality standards recommended by treatment guidelines, especially regarding psychological interventions.

Gender is associated with several features of psychotic disorders, including age of illness onset, symptomatology, a higher prevalence of history of childhood sexual abuse (CSA) and needs for care. Childhood sexual abuse is associated with adverse mental health consequences but as there is a gender difference in stress reactivity, there may be a differential impact of CSA on psychopathology, age of psychosis onset and needs for care in First Episode Psychosis (FEP) patients. We hypothesized that a history of abuse would be associated with lowering of age of onset, increased symptomatology and more unmet needs in women but not men. A total of 444 FEP patients have been recruited within the context of the GET UP trial. Symptomatology has been assessed using the PANSS scale, needs for care with the CAN scale and childhood abuse with the CECA-Q scale. Childhood sexual abuse was more frequent among female patients [22.6% in women vs 11.6% in men (OR = 0.45, p 0.01)], whereas there was no gender difference in the prevalence of childhood physical abuse (29.0% in women vs 31.7% in men). Childhood abuse was associated with higher levels of negative symptoms in both men and women, with a reduced age of onset in women only and little increase in needs for care in both men and women. Our results seem to suggest that childhood sexual abuse in female FEP patients may be linked to a more severe form of psychosis whose presentation is characterized by earlier age of onset and higher levels of negative symptoms and we can also speculate that gender-specific protective factors in women, but not in men, may be outweighed by the consequences of childhood abuse.

COMT Val(158)Met moderates the effect of stress on psychotic symptoms. Exposure to stress is also associated with mesolimbic dopamine release in individuals experiencing low maternal care. We therefore test the hypothesis that recent stressful life events are associated with more severe positive symptoms (associated with mesolimbic dopamine release) in first-episode psychosis (FEP) patients who experienced low maternal care during childhood. We hypothesized that COMT Val(158)Met moderates this association. A total of 149 FEP patients recruited within the Psychosis Incident Cohort Outcome Study (PICOS) participated in the present study. Maternal care was assessed by the Parental Bonding Instrument (PBI), stressful life events were collected by the List of Events Scale and positive symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). We found that low maternal care and recent stressful life events were associated with higher level of positive symptoms at the onset (analysis of variance [ANOVA], p = 0.012), and that patients who were also homozygotes for the COMT Val(158) allele had the highest level of positive symptoms (ANOVA, p = 0.024). Low maternal care and severe stressful life events may contribute to a symptomatology characterized by more severe positive symptoms at the onset, possibly due to an increased mesolimbic dopamine release. Homozygosity for the COMT Val(158) allele seems to confer a biological predisposition to the stress-related hyperactivity of the mesolimbic dopaminergic system. The data imply that the mesolimbic dopaminergic system is involved in the mediation/modulation of the effect of stressful events on the vulnerability for psychosis.

Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention: (1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services.

Currently, most of the classification studies of psychosis focused on chronic patients and employed single machine learning approaches. To overcome these limitations, we here compare, to our best knowledge for the first time, different classification methods of first-episode psychosis (FEP) using multi-modal imaging data exploited on several cortical and subcortical structures and white matter fiber bundles. 23 FEP patients and 23 age-, gender-, and race-matched healthy participants were included in the study. An innovative multivariate approach based on multiple kernel learning (MKL) methods was implemented on structural MRI and diffusion tensor imaging. MKL provides the best classification performances in comparison with the more widely used support vector machine, enabling the definition of a reliable automatic decisional system based on the integration of multi-modal imaging information. Our results show a discrimination accuracy greater than 90 % between healthy subjects and patients with FEP. Regions with an accuracy greater than 70 % on different imaging sources and measures were middle and superior frontal gyrus, parahippocampal gyrus, uncinate fascicles, and cingulum. This study shows that multivariate machine learning approaches integrating multi-modal and multisource imaging data can classify FEP patients with high accuracy. Interestingly, specific grey matter structures and white matter bundles reach high classification reliability when using different imaging modalities and indices, potentially outlining a prefronto-limbic network impaired in FEP with particular regard to the right hemisphere.

Hemodynamic changes in the brain have been reported in major psychosis in respect to healthy controls, and could unveil the basis of structural brain modifications happening in patients. The study of first episode psychosis is of particular interest because the confounding role of chronicity and medication can be excluded. The aim of this work is to automatically discriminate first episode psychosis patients and normal controls on the basis of brain perfusion employing a support vector machine (SVM) classifier. 35 normal controls and 35 first episode psychosis underwent dynamic susceptibility contrast magnetic resonance imaging, and cerebral blood flow and volume, along with mean transit time were obtained. We investigated their behavior in the whole brain and in selected regions of interest, in particular the left and right frontal, parietal, temporal and occipital lobes, insula, caudate and cerebellum. The distribution of values of perfusion indexes were used as features in a support vector machine classifier. Mean values of blood flow and volume were slightly lower in patients, and the difference reached statistical significance in the right caudate, left and right frontal lobes, and in left cerebellum. Linear SVM reached an accuracy of 83% in the classification of patients and normal controls, with the highest accuracy associated with the right frontal lobe and left parietal lobe. In conclusion, we found evidence that brain perfusion could be used as a potential marker to classify patients with psychosis, who show reduced blood flow and volume in respect to normal controls.

Outcome measurement, to be valid, reliable, and useful to both program planning and evaluation of interventions, should be based on the principle of multiaxiality (i.e., considering the perspectives of all those involved in the care process, including clinicians, patients, caregivers, users' representatives, third-party payers) and of multidimensionality (i.e., considering an intervention's effect on various dimensions of patients' life, including clinical outcomes such as psychopathology, disability, and needs for care and self-perceived outcomes such as quality of life and service satisfaction). Unfortunately, in Italy, this methodology has not been applied on a large scale. However, some Italian centers with a long-lasting tradition in the area of psychiatric epidemiology have provided evidence that outcome assessment in routine practice is not only sustainable but also advantageous in the medium- and long-term. This article summarizes the results obtained in some of these studies, including three longitudinal studies on the outcome of community psychiatric care promoted by the research group of South Verona, such as the South Verona Outcome Project, the Psychosis Incident Cohort Outcome Study, and the Genetics Endophenotypes and Treatment: Understanding early Psychosis -bullet; Psychosis: early Intervention and Assessment of Needs and Outcome trial.Implementation of routine outcome assessment can lead-and to a certain extent has already led-to a cultural change among Italian mental health service staff members, to facilitate a) the establishment of a revision-of-practice process, b) greater acceptance of the importance of evidence, and a predisposition to put it into practice.

This study aimed to describe patterns of experienced and anticipated discrimination in a sample of persons experiencing a first episode of psychosis and to explore associations with clinical and psychosocial variables.This cross-sectional survey was conducted within the context of the Psychosis Incident Cohort Outcome Study, a multisite naturalistic study examining first-episode patients treated in public psychiatric services in the Veneto Region of Italy. The Discrimination and Stigma Scale was used to assess experienced and anticipated discrimination.Ninety-seven patients were interviewed. Experiences of discrimination were common in relationships with family members (43%), making friends (32%), relationships with neighbors (25%), keeping a job (25%), finding a job (24%), and intimate relationships (23%). In regard to anticipated discrimination, 37% had stopped seeking a close relationship and 34% had stopped looking for work, 58% felt the need to conceal their diagnosis, and 37% reported that other people avoided them. In regression analysis, a higher number of functioning needs together with higher anticipated discrimination were associated with a higher level of experienced discrimination. A higher level of experienced discrimination and greater illness awareness were associated with more anticipated discrimination.First-episode patients reported experiencing discrimination in several key life areas. Anticipated discrimination further limited their access to life opportunities. Patients' awareness of the negative consequences of symptoms and disabilities led them to more easily perceive discrimination.

SummaryAims — To investigate in persons with mental disorders 1) the patterns of clinical course and their frequencies, 2) the impact of clinical course on two social dimensions of outcome, such as disability and quality of life. Methods — Study conducted with a longitudinal design in the “real world” of community mental health services. Clinical course was retrospectively assessed by using an instrument developed by our group, taking into account previous literature in this area; disability and quality of life were measured, respectively, with the WHO—Disability Assessment Schedule and the Lancashire Quality of Life Profile. Results — In patients with non affective psychosis, continuous and episodic course showed the same tendency to occur, whereas in subjects with affective disorders (either psychotic or neurotic) episodic course was more frequent. Continuous course was associated with higher levels of disability and lower quality of life in psychotic patients, while a poorer quality of life in some areas was associated with episodic course in patients with non psychotic disorders. Conclusions — The impact of clinical course on social disability and quality of life is different depending upon the specific diagnostic category. This suggests that specific and individualised interventions should be provided in order to prevent the negative impact of clinical course on life conditions of persons with mental disorders.Declaration of Interestthe study has been supported by a Grant from MURST 60% to Prof. Mirella Ruggeri and Fondi 1% per la Ricerca Sanitaria Finalizzata 2001 Ministry of Health, to Professor M. Tansella.

Background Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in ‘real-world’ services. Methods/Design The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers’ patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrolment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms’ severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in ‘real-world’ clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction. Trial registration ClinicalTrials.gov Identifier NCT01436331