Katia De Santi

The impact of cannabis use on age of onset and clinical characteristics in first-episode psychotic patients. Data from the Psychosis Incident Cohort Outcome Study (PICOS)

Cannabis use is frequent among first-episode psychosis (FEP) patients and has been associated with several clinical features. This study aimed in an FEP sample to determine whether cannabis use is associated with (1) a higher level of positive symptoms, a lower level of depression and a better premorbid adjustment, (2) an earlier age of onset, and a better premorbid IQ. The study was conducted within the framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite collaborative research on FEP patients who attended the psychiatric services in Veneto Region, Italy. Standardized instruments were used to collect sociodemographic, clinical, and drug use data. A total of 555 FEP patients met the inclusion criteria, 517 of whom received an ICD-10 diagnosis of psychosis; 397 (55% males; mean age: 32 yrs ± 9.5) were assessed. Out of these, 311 patients agreed to be interviewed on drug and alcohol misuse; 20.3% was positive for drug misuse: cannabis (19.0%), cocaine (3.9%), and hallucinogens (3.9%). Cannabis use was not associated with a higher level of positive symptoms, but correlated with less severe depressive symptoms. No relationship was observed between premorbid adjustment or IQ and cannabis use. FEP patients who used cannabis had an earlier age of onset than abstinent patients, even after adjusting for gender and diagnosis. Our results suggest a possible causal role of cannabis in triggering psychosis in certain vulnerable subjects. Particular attention must be paid to this behaviour, because reducing cannabis use can delay or prevent some cases of 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.

First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation

BACKGROUND Considerable variations in the incidence of psychosis have been observed across countries, in terms of age, gender, immigration status, urbanicity and socioeconomic deprivation. AIMS To evaluate the incidence rate of first-episode psychosis in a large area of north-eastern Italy and the distribution of the above-mentioned risk factors in individuals with psychoses. METHOD Epidemiologically based survey. Over a 3-year period individuals with psychosis on first contact with services were identified and diagnosed according to ICD-10 criteria. RESULTS In total, 558 individuals with first-episode psychosis were identified during 3,077,555 person-years at risk. The annual incidence rate per 100,000 was 18.1 for all psychoses, 14.3 for non-affective psychoses and 3.8 for affective psychoses. The rate for all psychoses was higher in young people aged 20-29 (incidence rate ratio (IRR) = 4.18, 95% CI 2.77-6.30), immigrants (IRR = 2.26, 95% CI 1.85-2.75) and those living in the most deprived areas (IRR = 2.09, 95% CI 1.54-2.85). CONCLUSIONS The incidence rate in our study area was lower than that found in other European and North American studies and provides new insights into the factors that may increase and/or decrease risk for developing psychosis.

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.

BackgroundMulti-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/DesignThe 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 registrationClinicalTrials.gov Identifier NCT01436331

The use of dynamic susceptibility contrast (DSC) MRI to automatically classify patients with first episode psychosis

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.

Positive symptoms in first-episode psychosis patients experiencing low maternal care and stressful life events: a pilot study to explore the role of the COMT gene.

Abstract COMT Val158Met 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 Val158Met 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 Val158 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 Val158 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.

Outcomes from Italian community psychiatric services studies.

Abstract 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 - • 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.