Incidental findings on brain MRI in patients with first-episode and chronic psychosis.

Brain incidental findings (IFs) are unexpected brain abnormalities detected by a structural magnetic resonance (MRI) examination. We conducted a study to assess whether brain IFs are associated with first-episode psychosis (FEP) and chronic psychosis (affective vs. non-affective) compared to healthy controls (HC). Chi-squared analyses were run to compare the frequency of several IFs across groups. Logistic regression analyses were run to explore the association between group and IFs, accounting for sex, age, MRI field strength. We observed a higher frequency of most IFs in both FEP and chronic psychosis groups compared to HC, however most of the chi-squared tests did not reach significance. Patients with FEP and chronic psychosis were 3-4 times more likely to show deep white matter hyperintensities (WMH) than HC. Patients with FEP and affective chronic psychosis were 3-4 times more likely to show ventricular asymmetries than HC. All chronic patients were more likely to show periventricular WMH, liquoral spaces enlargements and ventricular system enlargements respectively. Our results suggest that deep WMH and ventricular asymmetries are associated with both the early and the chronic stages of psychosis, thus representing potential vulnerability factors already present before the onset of the symptoms, possibly due to neurodevelopmental insults.

Early intervention service for first episode psychosis in Modena, Northern Italy: The first hundred cases.

AIM: To report on the development of an early intervention service in Modena, Italy, with information relevant to the first 4 years of implementation. METHODS: The 2-year service was offered to people aged 18-35 with psychotic manifestations, within 2 years from psychosis onset/or naïve to antipsychotics, by teams placed within community mental health Centres, according to a "specialist within generalist" model. Treatment included pharmacological consultation, psychoeducation and social inclusion programs. Health of the Nation Outcome Scale was administered at baseline and every 6 months. RESULTS: One hundred cases accepted the treatment from 1 March 2013 to 31 December 2016. Of these, 71% were male with a median age of 23. Ninety percent were diagnosed with non-affective psychosis, yielding an estimated treated incidence of 19.1/105 . General practitioners (GPs)represented the most frequent referrers to the program (38%), followed by referrals from acute general and psychiatric hospital units (22%) and self-referrals (14%). Meaningful clinical improvement was observed, 6 months after enrolment. CONCLUSIONS: An early intervention service for psychosis was successfully implemented within existing community outpatient services. GPs represented the main referrals, providing some validation of the "specialist within generalist" model of care. A promising clinical improvement and trend of reduction in duration of untreated psychosis was found, supporting the variety of early detection efforts in the community. The high median age and lack of information about pathways to care underline possible barriers to access for younger patients. These findings will inform refinement of treatments and service models for the Region.

Prosody abilities in a large sample of affective and non-affective first episode psychosis patients.

OBJECTIVE: Prosody comprehension deficits have been reported in major psychoses. It is still not clear whether these deficits occur at early psychosis stages. The aims of our study were to investigate a) linguistic and emotional prosody comprehension abilities in First Episode Psychosis (FEP) patients compared to healthy controls (HC); b) performance differences between non-affective (FEP-NA) and affective (FEP-A) patients, and c) association between symptoms severity and prosodic features. METHODS: A total of 208 FEP (156 FEP-NA and 52 FEP-A) patients and 77 HC were enrolled and assessed with the Italian version of the "Protocole Montréal d'Evaluation de la Communication" to evaluate linguistic and emotional prosody comprehension. Clinical variables were assessed with a comprehensive set of standardized measures. RESULTS: FEP patients displayed significant linguistic and emotional prosody deficits compared to HC, with FEP-NA showing greater impairment than FEP-A. Also, significant correlations between symptom severity and prosodic features in FEP patients were found. CONCLUSIONS: Our results suggest that prosodic impairments occur at the onset of psychosis being more prominent in FEP-NA and in those with severe psychopathology. These findings further support the hypothesis that aprosodia is a core feature of psychosis.

Hippocampal Subfield Volumes in Patients With First-Episode Psychosis.

Background: Hippocampal abnormalities have been largely reported in patients with schizophrenia and bipolar disorder, and are considered to be involved in the pathophysiology of the psychosis. The hippocampus consists of several subfields but it remains unclear their involvement in the early stages of psychosis. Aim: The aim of this study was to investigate volumetric alterations in hippocampal subfields in patients at the first-episode psychosis (FEP). Methods: Magnetic resonance imaging (MRI) data were collected in 134 subjects (58 FEP patients; 76 healthy controls [HC]). A novel automated hippocampal segmentation algorithm was used to segment the hippocampal subfields, based on an atlas constructed from ultra-high resolution imaging on ex vivo hippocampal tissue. The general linear model was used to investigate volume differences between FEP patients and HC, with age, gender and total intracranial volume as covariates. Results: We found significantly lower volumes of bilateral CA1, CA4, and granule cell layer (GCL), and of left CA3, and left molecular layer (ML) in FEP patients compared to HC. Only the volumes of the left hippocampus and its subfields were significantly lower in FEP than HC at the False Discovery Rate (FDR) of 0.1. No correlation was found between hippocampal subfield volume and duration of illness, age of onset, duration of medication, and Positive and Negative Syndrome Scale (PANSS). Conclusion: We report abnormally low volumes of left hippocampal subfields in patients with FEP, sustaining its role as a putative neural marker of psychosis onset.

Effectiveness of a social inclusion program in people with non-affective psychosis.

BACKGROUND: People with psychotic illness suffer from reduced quality of life and often from an insufficient level of social inclusion. These variables are associated with several negative outcomes, such as higher neuro-cognitive deficits, negative symptoms, internalised stigma, increased cardiovascular risk and, most importantly, excess mortality. To date, only a minority of social interventions in psychosis have been investigated. Since 2011, the Department of Mental Health and Substance Abuse in Modena introduced the "Social Point" program, which provides social inclusion interventions to promote active social participation for patients suffering from severe mental illness. The aim of this study was to assess whether a social inclusion intervention is associated with better outcomes in terms of personal and social recovery, with particular reference to the areas of social functioning and activity, and subjective dimensions such as self-esteem, self-stigma and perceived quality of life. METHODS: A cross-sectional design was adopted to compare 30 subjects, selected at the completion of "Social Point" program, with a group of subjects, matched for socio-demographic and clinical features, selected from a wait list for "Social Point". All subjects were evaluated by means of instruments assessing: level of disability, level of functioning, severity of psychopathology, self-esteem, internalised stigma and quality of life. RESULTS: Overall, the results of the study suggest that social inclusion interventions may be effective in people suffering from non-affective psychosis. A dose-effect relationship was also found between higher number of activities per patient and better outcomes within both social and psychopathological domains. However, due to the cross-sectional design of the study no definitive causality can be inferred. CONCLUSION: Psychosocial interventions promoting social inclusion are likely to represent an effective approach to improve personal and social recovery.

Classification of first-episode psychosis in a large cohort of patients using support vector machine and multiple kernel learning techniques.

First episode psychosis (FEP) patients are of particular interest for neuroimaging investigations because of the absence of confounding effects due to medications and chronicity. Nonetheless, imaging data are prone to heterogeneity because for example of age, gender or parameter setting differences. With this work, we wanted to take into account possible nuisance effects of age and gender differences across dataset, not correcting the data as a pre-processing step, but including the effect of nuisance covariates in the classification phase. To this aim, we developed a method which, based on multiple kernel learning (MKL), exploits the effect of these confounding variables with a subject-depending kernel weighting procedure. We applied this method to a dataset of cortical thickness obtained from structural magnetic resonance images (MRI) of 127 FEP patients and 127 healthy controls, who underwent either a 3Tesla (T) or a 1.5T MRI acquisition. We obtained good accuracies, notably better than those obtained with standard SVM or MKL methods, up to more than 80% for frontal and temporal areas. To our best knowledge, this is the largest classification study in FEP population, showing that fronto-temporal cortical thickness can be used as a potential marker to classify patients with psychosis.

Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants.

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.

Understanding psychopathology in migrants: a mixed categorical-dimensional approach.

BACKGROUND: Literature on mental disorders in migrants is constantly increasing. Only a few studies describe psychopathological dimensions in migrants over their nosographic diagnoses; however, there is a growing literature about the greater utility of a categorical-dimensional approach, rather than a solely categorical approach, in the understanding of mental disorders. The aim of this paper is to describe the phenomenology of mental disorders in migrants referred to the Transcultural Psychiatric Team of Bologna (BoTPT), by analysing the psychopathological dimensions that underlie their clinical diagnoses. METHODS: We recruited all migrants who attended the BoTPT between May 1999 and July 2009. The psychopathological assessment was conducted with the Association for Methodology and Documentation in Psychiatry (AMDP) and clinical diagnoses were formulated according to ICD-10. We proceeded through a two-step analysis: (1) comparing the prevalence rates of psychopathological symptoms across diagnoses; then (2) conducting a factor analysis to assess how those symptoms configure psychopathological dimensions and how these dimensions underlie clinical diagnoses. RESULTS: As expected, we found significant associations between diagnoses and the prevalence of their core psychopathological symptoms. Factor analysis revealed a strong polymorphism of the psychopathological presentation of mental disorders and unexpectedly showed that in each diagnostic cluster, the first extracted factor was not composed of core symptoms. CONCLUSIONS: A mixed categorical-dimensional approach seems to improve the description of the psychopathology among migrants, as it adds relevant information regarding psychopathological dimensions useful to the understanding of the peculiar clinical expressivity of our patients.

[The neuropsychology of prodromal schizophrenia. Brief review and proposal of a tests battery for clinical use]. / Neuropsicologia dell'esordio schizofrenico. Breve rassegna della letteratura e proposta di una batteria di test per l'uso clinico.

The study of the neuropsychological profile of schizophrenic patients has provided systematic results in linking specific deficit (working memory, verbal learning, attentive and executive functioning, social cognition) to the functional outcome of subjects. More recently this approach has been applied to younger subjects, from the age of 14, that show prodromal signs of a possible psychotic conversion (ultra-risk subjects). The review is at first intended to describe the clinical and experimental studies that investigated the cognitive and neuropsychological profile of subjects at ultra-risk for psychosis. These studies show the presence of minor cognitive difficulties in several specific areas (working memory, verbal learning, attentive and executive functioning) that can be indicative of both a possible conversion to psychosis and a need for cognitive remediation programs. Secondarily, the article describes several neuropsychological tools, standardized for the Italian population, that can be used to approach the clinical assessment of ultra-risk subjects considering some critical aspects such as their typical age range (adolescents and young adults).

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial.

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 enrollment 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.

Stigma and discrimination toward mental illness: translation and validation of the Italian version of the Attribution Questionnaire-27 (AQ-27-I).

PURPOSE: The aim of this study was to translate the Attribution Questionnaire-27 (AQ-27) to the Italian language (AQ-27-I), and to examine the reliability and validity of this new Italian version. METHODS: The questionnaire was translated using the standard translation/back-translation method. Cronbach's alpha and intraclass coefficients were used to estimate instrument reliability. Confirmatory factor analysis was conducted to corroborate the original English version factor structure in the new measure, and to establish validity. Path analyses were meant to validate relationships found in the English version among Italian-speaking participants. RESULTS: The AQ-27-I demonstrated acceptable internal consistency, with a Cronbach's alpha of 0.82 for the total scale and ranging between 0.52 and 0.91 for the subscales. The test-retest reliability was also satisfactory, with intraclass correlation coefficients of 0.72 for the total scale and ranging between 0.51 and 0.89 for the subscales. Fit indices of the model supported the factor structure and paths. CONCLUSIONS: The AQ-27-I is a reliable measure to assess stigmatizing attitudes in Italian.

Prevalence of common mental disorders in Italy: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD).

OBJECTIVE: To present 1-month, 12-month and lifetime prevalence estimates of mood, anxiety and alcohol disorders in Italy; and the socio-demographic correlates and comorbidity patterns of these estimated disorders. METHOD: A representative random sample of non-institutionalised citizens of Italy aged 18 or older (N=4,712) was interviewed between January 2001 and July 2003, with a weighted response rate of 71.3%. DSM-IV disorders were assessed by lay interviewers using Version 3.0 of the Composite International Diagnostic Interview (CIDI). RESULTS: A total of 11% of respondents reported a lifetime history of any mood disorder, 10.3% any anxiety disorder and 1.3% any alcohol disorder. About 5% reported having an anxiety disorder in the past 12 months compared to 3.3% for any mood disorder and 0.2% for any alcohol disorder. Major depression and specific phobia were the most common mental disorders. Women were twice as likely as men to report a mood disorder and four times as likely as men to report an anxiety disorder, while men were twice as likely as women to report an alcohol disorder. High comorbidity of mood and anxiety disorders was observed. Prevalence estimates were generally lower than in parallel surveys carried out in other Western European countries. CONCLUSION: A high proportion of adults in Italy have a history of mood, anxiety or alcohol disorders. The lower than expected prevalence estimate of alcohol use disorder may be due to under-reporting or to low social harm from alcohol consumption.

Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys.

The DSM-IV diagnoses generated by the fully structured lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) in the WHO World Mental Health (WMH) surveys were compared to diagnoses based on follow-up interviews with the clinician-administered non-patient edition of the Structured Clinical Interview for DSM-IV (SCID) in probability subsamples of the WMH surveys in France, Italy, Spain, and the US. CIDI cases were oversampled. The clinical reappraisal samples were weighted to adjust for this oversampling. Separate samples were assessed for lifetime and 12-month prevalence. Moderate to good individual-level CIDI-SCID concordance was found for lifetime prevalence estimates of most disorders. The area under the ROC curve (AUC, a measure of classification accuracy that is not influenced by disorder prevalence) was 0.76 for the dichotomous classification of having any of the lifetime DSM-IV anxiety, mood and substance disorders assessed in the surveys and in the range 0.62-0.93 for individual disorders, with an inter-quartile range (IQR) of 0.71-0.86. Concordance increased when CIDI symptom-level data were added to predict SCID diagnoses in logistic regression equations. AUC for individual disorders in these equations was in the range 0.74-0.99, with an IQR of 0.87-0.96. CIDI lifetime prevalence estimates were generally conservative relative to SCID estimates. CIDI-SCID concordance for 12-month prevalence estimates could be studied powerfully only for two disorder classes, any anxiety disorder (AUC = 0.88) and any mood disorder (AUC = 0.83). As with lifetime prevalence, 12-month concordance improved when CIDI symptom-level data were added to predict SCID diagnoses. CIDI 12-month prevalence estimates were unbiased relative to SCID estimates. The validity of the CIDI is likely to be under-estimated in these comparisons due to the fact that the reliability of the SCID diagnoses, which is presumably less than perfect, sets a ceiling on maximum CIDI-SCID concordance.