A machine learning approach on whole blood immunomarkers to identify an inflammation-associated psychosis onset subgroup.

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis.

Exploring gender impact on collaborative care planning: insights from a community mental health service study in Italy.

INTRODUCTION: Personal recovery is associated with socio-demographic and clinical factors, and gender seems to influence the recovery process. This study aimed to investigate: i) differences in the recovery goals of men and women users of a community mental health service in Italy; ii) any differences by gender in recovery over six months using the Mental Health Recovery Star (MHRS). METHODS: Service users and staff completed the MHRS together at recruitment and six months later to agree the recovery goals they wished to focus on. Socio-demographic and clinical characteristics and ratings of symptoms (BPRS), needs (CAN), functioning (FPS), and functional autonomy (MPR) were collected at recruitment and six months follow-up. Comparisons between men and women were made using t-tests. RESULTS: Ten women and 15 men completed the MHRS with 19 mental health professionals. Other than gender, men and women had similar socio-demographic, and clinical characteristics at recruitment. Women tended to choose recovery goals that focused on relationships whereas men tended to focus on work related goals. At follow-up, both men and women showed improvement in their recovery (MHRS) and women were less likely to focus on relationship related goals, perhaps because some had found romantic partners. There were also gains for both men and women in engagement with work related activities. Ratings of functional autonomy (MPR) improved for both men and women, and men also showed improvement in symptoms (BPRS) and functioning (FPS). CONCLUSIONS: Our findings suggest that collaborative care planning tools such as the MHRS can assist in identifying individualized recovery goals for men and women with severe mental health problems as part of their rehabilitation.

Childhood adversity, symptoms, and cortisol in first episode psychosis: a cross-sectional, secondary, observational analysis of a subsample of FEP patients.

BACKGROUND: Although it has been proposed that childhood adversities (CAs) may affect the hypothalamic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP patients. METHODS: 81 FEP patients were enrolled. CAs were evaluated by the Childhood Experience of Care and Abuse Questionnaire and a semi-structured interview. Psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale. Cortisol level was collected using saliva samples. ANCOVA and partial correlation analyses were run. RESULTS: FEP patients with childhood abuse reported severe positive symptoms than those without CA. FEP patients with at least one CA had higher levels of cortisol awaking, cortisol at 12 a.m., and cortisol at 8 p.m. Morning cortisol levels were negatively correlated with the severity of negative symptoms and positively correlated with the severity of general psychopathology. Evening cortisol levels were positively correlated with severity of general psychopathology. CONCLUSION: FEP patients with CAs, compared with those without CA, might report more severe positive symptoms and higher cortisol, even though these findings as prone to bias due to the small sample size, and should be seen in the larger perspective of conflicting evidence in the field.

Supported employment for people with severe mental illness: a pilot study of an Italian social enterprise with a special ingredient.

BACKGROUND: People with mental disorders are far more likely to be unemployed than the general population. Two internationally recognized, evidence-based models of interventions for employment for people with severe mental health problems are Individual Placement Support and the Clubhouse. In Italy, a common model is the 'social enterprise' (SE), which is a programme run by non-profit organisations that help individuals with disabilities to be employed. Despite SEs spread and relevance in Italy, there are no studies about Italian samples. This paper reports on a pilot evaluation of psychosocial and work outcomes of a SE based in Verona, Italy. The study aims to investigate if people with SMI involved in SE job placements may achieve personal recovery and better outcomes over time, and in comparison with a comparable group of users. METHODS: This is a pilot descriptive study with three components. A longitudinal design that comprised a functioning description of 33 SE members with a psychiatric disability in two time-points (when they joined the SE-on average 5 years before the study recruitment, and at the study recruitment-year 2018); and a repeated collection of job details of the 33 members in three time points: 2 years before the recruitment,-year 2016; 1 year before the recruitment - year 2017; and at the recruitment-year 2018. An assessment at the recruitment time-year 2018, of SE users' satisfaction with the job placement, symptoms, functioning, and quality of life (QoL). A cross-sectional study that compared the 33 SE members at the recruitment time-year 2018, with a matched group of people with the following criteria: living in local supported accommodations, being unemployed and not SE members. The two groups were compared on ratings of psychopathology, functioning, and QoL. Descriptive analyses were done. RESULTS: At the recruitment time - year 2018, all SE participants showed a significant better functioning (p < 0.001) than when they joined the SE-when they had been employed for an average of 5 years. In comparison to the matched group, SE members had significantly better functioning (p = 0.001), psychopathology (p = 0.007), and QoL (p = 0.034). According to their SE membership status, participants comprised trainees (21.2%) and employee members (78.8%). Trainees compared to employees had lower autonomies, functioning, QoL and more severe psychopathology. Over the two years prior to study recruitment, trainees showed stable poor autonomies, while employee members showed a variation from average autonomies in the 2 years before the recruitment time - year 2016, to good ones at the recruitment time - year 2018. Over the two years, all SE members set increasing numbers of objectives in all three domains. All SE participants reported high levels of satisfaction with all aspects of the job placement. CONCLUSIONS: SE that provides tailored support to assist people to gain employment skills may be an effective component in helping recovery from SMI.

Quality of residential facilities in Italy: satisfaction and quality of life of residents with schizophrenia spectrum disorders.

BACKGROUND: Recovery and human rights promotion for people with Schizophrenia Spectrum Disorders (SSDs) is fundamental to provide good care in Residential Facilities (RFs). However, there is a concern about rehabilitation ethos in RFs. This study aimed to investigate the care quality of Italian RFs, the quality of life (QoL) and care experience of residents with SSD. METHODS: Fourty-eight RFs were assessed using a quality assessment tool (QuIRC-SA) and 161 residents with SSD were enrolled. Seventeen RFs provided high intensity rehabilitation (SRP1), 15 medium intensity (SRP2), and 16 medium-low level support (SRP3). Staff-rated tools measured psychiatric symptoms and psychosocial functioning; user-rated tools assessed QoL and satisfaction with services. RFs comparisons were made using ANOVA and Chi-squared. RESULTS: Over two-thirds patients (41.5 y.o., SD 9.7) were male. Seventy-six were recruited from SRP1 services, 48 from SRP2, and 27 from SRP3. The lowest QuIRC-SA scoring was Recovery Based Practice (45.8%), and the highest was promotion of Human Rights (58.4%). SRP2 had the lowest QuIRC-SA ratings and SRP3 the highest. Residents had similar psychopathology (p = 0.140) and functioning (p = 0.537). SRP3 residents were more employed (18.9%) than SRP1 (7.9%) or SRP2 (2.2%) ones, and had less severe negative symptoms (p = 0.016) and better QoL (p = 0.020) than SRP2 residents. There were no differences in the RF therapeutic milieu and their satisfaction with care. CONCLUSIONS: Residents of the lowest supported RFs in Italy had less severe negative symptoms, better QoL and more employment than others. The lowest ratings for Recovery Based Practice across all RFs suggest more work is needed to improve recovery.

Performance and effectiveness of step progressive care pathways within mental health supported accommodation services in Italy.

BACKGROUND: In Italy, a growing number of people with severe mental illness (SMI) require care in residential facilities (RFs), a key component of the care pathway. However, despite their development, studies about resident samples have been very few. AIMS: This study, the VALERE-REC Study (eVALuation of outcomE in Residential-use of clinical data with REsearch objeCtives) aims to identify the characteristics that increase the probability to move patients living in RFs to a more independent setting. METHODS: A survey involved 167 patients hosted in 25 RFs of the Verona Mental Health Department. Forty-five patients were residents (27%) in Comunità Terapeutico Riabilitativa Protetta (CTRP); 56 (34%) in Comunità Alloggio (CA), 14 (8%) in Gruppo Appartamento Protetto (GAP), 52 (31%) in Comunità Alloggio Estensiva (CAE). They were assessed for their care pathway after 30-months. The Quality Indicators for Rehabilitative Care-Supported Accommodation (QuIRC-SA) evaluated the quality of 19/25 (76%) RFs. Descriptive analyses were done. RESULTS: According to the mission stated by the Veneto Region guidelines, RFs hosted patients with different needs and clinical profiles. The mean stay was longer than expected, most patients were unemployed, unmet needs were related to self-management and patient's social contacts, and recovery-oriented practices were not implemented. CONCLUSIONS: Despite the appropriate admission of patients in different RFs considering their psychopathology, functioning, and needs, the progressive step care pathway did not result effectively pursued. To improve the effectiveness of residential interventions a major task should be to focus on the acquisition of the necessary skills to live independently.

Do outcomes of psychiatric hospital treatment differ for migrants and non-migrants?

PURPOSE: Providing effective treatment for immigrants is an increasing challenge for mental health services across Europe. Yet, little is known as to whether current practice is associated with different outcomes in migrant and non-migrant patients. We compared outcomes of inpatient psychiatric treatment for migrants and non-migrants in a sample from five European countries. METHODS: Patients with psychotic disorders, affective disorders or anxiety/somatisation disorders admitted to routine psychiatric inpatient treatment were assessed in hospitals in Belgium, Germany, Italy, Poland and the United Kingdom. Treatment outcomes were satisfaction with care during hospitalisation, length of stay, readmission to hospital (any and, specifically, involuntary re-hospitalisation), as well as untoward incidents in a 1-year follow-up period. Outcomes were compared between patients born inside (non-migrants) and outside (migrants) the country of treatment, through mixed regression models. RESULTS: Across all sites, 985 migrant patients and 6298 non-migrant patients were included. After accounting for the influence of confounding patient characteristics, migrants reported significantly lower treatment satisfaction, but there were no significant differences for length of stay and re-hospitalisations, in general and involuntary ones. Migrants had a lower rate of suicide attempts, but there was no significant difference in other types of untoward incidents in the year following the index admission. CONCLUSION: The study suggests that migrants are less satisfied with their hospital treatment, there is no evidence that routine inpatient care as currently provided results overall in poorer objective outcomes for migrants than in non-migrant populations.

Should we be concerned about stigma and discrimination in people at risk for psychosis? A systematic review.

BACKGROUND: Previous studies have provided initial evidence that people at risk for psychosis (PR) suffer from stigma and discrimination related to their condition. However, no study has systematically reviewed stigma and discrimination associated with being at PR and the potential underlying mechanisms. METHODS: This work aimed to systematically review all studies addressing stigma and discrimination in PR people in order to assess: (1) the occurrence of this phenomenon and its different components (public, internalized, perceived, and labeling-related), (2) whether stigma affects outcomes of the PR state, and (3) whether other factors modulate stigma among PR individuals. RESULTS: The reviewed studies (n = 38) widely differ in their design, methodological quality, and populations under investigation, thus limiting direct comparison of findings. However, converging evidence suggests that the general public endorses stigmatizing attitudes towards PR individuals, and that this is more frequent in people with a low educational level or with no direct experience of the PR state. PR individuals experience more internalized stigma and perceive more discrimination than healthy subjects or patients with non-psychotic disorders. Further, PR labeling is equally associated with both positive (e.g. validation and relief) and negative effects (e.g. status loss and discrimination). Moreover, stigma increases the likelihood of poor outcome, transition to full-psychosis, disengagement from services, and family stigma among PR individuals. Finally, very limited evidence awaiting replication supports the efficacy of cognitive therapies in mitigating the negative effects of stigma. CONCLUSIONS: Evidence confirms previous concerns about stigma and its negative consequences for PR individuals, thus having important public health implications.

Factors associated with satisfaction of inpatient psychiatric care: a cross country comparison.

BACKGROUND: Patient satisfaction is a key indicator of inpatient care quality and is associated with clinical outcomes following admission. Different patient characteristics have been inconsistently linked with satisfaction. This study aims to overcome previous limitations by assessing which patient characteristics are associated with satisfaction within a large study of psychiatric inpatients conducted across five European countries. METHODS: All patients with a diagnosis of psychotic (F2), affective (F3) or anxiety/somataform (F4) disorder admitted to 57 psychiatric inpatient units in Belgium, Germany, Italy, Poland and the UK were included. Data were collected from medical records and face-to-face interviews, with patients approached within 2 days of admission. Satisfaction with inpatient care was measured on the Client Assessment of Treatment Scale. RESULTS: Higher satisfaction scores were associated with being older, employed, living with others, having a close friend, less severe illness and a first admission. In contrast, higher education levels, comorbid personality disorder and involuntary admission were associated with lower levels of satisfaction. Although the same patient characteristics predicted satisfaction within the five countries, there were significant differences in overall satisfaction scores across countries. Compared to other countries, patients in the UK were significantly less satisfied with their inpatient care. CONCLUSIONS: Having a better understanding of patient satisfaction may enable services to improve the quality of care provided as well as clinical outcomes for all patients. Across countries, the same patient characteristics predict satisfaction, suggesting that similar analytical frameworks can and should be used when assessing satisfaction both nationally and internationally.

Gender and 5-years course of psychosis patients: focus on clinical and social variables.

Most studies on gender and psychosis have focused on gender differences at illness onset or on the long-term outcome, whereas little is known about the impact of gender on the first years after psychosis onset. A total of 185 first episode psychosis (FEP) patients were followed for 5 years after psychosis onset, and gender differences were explored in psychopathology (PANSS), needs for care (CAN), and insight (SAI-E). Male patients showed more negative symptoms than females over time, whereas female patients showed higher levels of depressive symptoms than males throughout the study period. In addition, female patients presented more functioning unmet needs for care, but higher levels of insight into illness than males. Therapy and rehabilitative programs for FEP patients should be gender-targeted, as gender has proved to impact on psychopathology, needs for care, and insight in the very first years following psychosis onset.

Predicting Patients' Readmission: Do Clinicians Outperform a Statistical Model? An Exploratory Study on Clinical Risk Judgment in Mental Health.

This study explores whether clinicians or a statistical model can better identify patients at risk of early readmission and investigates variables potentially associated with clinicians' risk judgment. We focus on a total of 142 patients discharged from acute psychiatric wards in the Verona Mental Health Department (Italy). Psychiatrists assessed patients' risk of readmission at 30 and 90 days postdischarge, predicted their postdischarge compliance, and assessed their Global Assessment of Functioning (GAF) score at admission and discharge. Clinicians' judgment outperformed the statistical model, with the difference reaching statistical significance for 30-day readmission. Clinicians' readmission risk judgment, both for 30 and 90 days, was found to be statistically associated with predicted compliance with community treatment and GAF score at discharge. Clinicians' superior performance might be explained by their risk judgment depending on nonmeasurable factors, such as experience and intuition. Patients with a poorer GAF score at discharge and poor assumed compliance were predicted to have a higher risk of readmission.

Use of psychiatric hospitals and social integration of patients with psychiatric disorders: a prospective cohort study in five European countries.

PURPOSE: Long lengths of stay (LoS) in psychiatric hospitals or repeated admission may affect the social integration of patients with psychiatric disorders. So far, however, studies have been inconclusive. This study aimed to analyse whether long LoS or repeated admissions in psychiatric wards were associated in different ways with changes in the social integration of patients. METHODS: Within a prospective cohort study, data were collected on 2181 patients with a main ICD-10 diagnosis of psychotic, affective, or anxiety disorder, hospitalised in the UK, Italy, Germany, Poland, and Belgium in 2015. Social integration was measured at baseline and 1 year after admission using the SIX index, which includes four dimensions: employment, housing, family situation, and friendship. Regression models were performed to test the association between LoS, the number of admissions, and the change in social integration over the study period, controlling for patients' characteristics (trial registration ISRCTN40256812). RESULTS: A longer LoS was significantly associated with a decrease in social integration (ß = - 0.23, 95%CI - 0.32 to - 0.14, p = 0.03), particularly regarding employment (OR = 2.21, 95%CI 1.18-3.24, p = 0.02), housing (OR = 3.45, 95%CI 1.74-5.16, p < 0.001), and family situation (OR = 1.94, 95%CI 1.10-2.78, p = 0.04). In contrast, repeated admissions were only associated with a decrease in friendship contacts (OR = 1.15, 95CI% 1.08-1.22, p = 0.03). CONCLUSIONS: Results suggest that a longer hospital LoS is more strongly associated with a decrease in patients' social integration than repeated admissions. Special attention should be paid to helping patients to find and retain housing and employment while hospitalised for long periods.

Personal continuity versus specialisation of care approaches in mental healthcare: experiences of patients and clinicians-results of the qualitative study in five European countries.

BACKGROUND: The current debate on organisation of the mental health care raises a question whether to prioritise specialisation of clinical teams or personal continuity of care. The article explores the experiences of patients and clinicians regarding specialisation (SC) and personal continuity (PCC) of care in five European countries. METHODS: Data were obtained via in-depth, semi-structured interviews with patients (N = 188) suffering from mental disorders (F20-49) and with clinicians (N = 63). A maximum variation sampling was applied to assume representation of patients and of clinicians with different characteristics. The qualitative data from each country were transcribed verbatim, coded and analysed through a thematic analysis method. RESULTS: Many positive experiences of patients and clinicians with the PCC approach relate to the high quality of therapeutic relationship and the smooth transition between hospital and community care. Many positive experiences of patients and clinicians with the SC approach relate to concepts of autonomy and choice and the higher adequacy of diagnosis and treatment. Clinicians stressed system aspects of providing mental health care: more effective management structure and higher professionalization of care within SC approach and the lower risk of disengagement from treatment and reduced need for coercion, restraint, forced medication or involuntary admission within PCC. CONCLUSIONS: Neither the PCC, nor the SC approach meets the needs and expectations of all patients (and clinicians). Therefore, future reforms of mental health services should offer a free choice of either approach, considering that there is no evidence of differences in patient outcomes between PCC and SC approaches.

Pathways to care, DUP, and types of interventions over 5 years following psychosis onset: findings from a naturalistic study conducted in routine generalist mental health services.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme.

PURPOSE: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. METHODS: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. CONCLUSIONS: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study [corrected].

Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = - 0.51, p = 0.04) and in male BD patients (r = - 0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Correction to: Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study.

In the original publication of the article, the title was incorrect. The correct title should read as given below.

Mental health supported accommodation services in England and in Italy: a comparison.

PURPOSE: England and Italy are considered pioneers in the development of community mental health services. Both have implemented supported accommodation services for those with more complex needs, which can be broadly categorized into three main types with similar specification. The aim of this study was to compare the characteristics of these services and their users in England and Italy. METHODS: Data from two cross-sectional surveys of supported accommodation services undertaken across England and in Verona, Italy (England-619 service users from 87 services; Verona-167 service users from 25 services) were compared. RESULTS: Service users in the two samples had similar socio-demographic and clinical characteristics; most were male, unmarried and unemployed, with a primary diagnosis of schizophrenia or other psychosis and over 15 years contact with mental health services. Supported accommodation occupancy was high in both samples. The actual length of stay was greater than the expected length of stay for all three service types but overall turnover was similar between countries (p = 0.070). Across services, total needs and quality of life were higher for Italian compared to English service users (p < 0.001 for both) but, unmet needs were lower amongst English service users (p < 0.001). Around 40% in both samples moved to more independent accommodation successfully within 30 months. CONCLUSIONS: England and Italy have similar mental health supported accommodation pathways to assist those with more complex needs to gain skills for community living, but individuals tend to require longer than expected at each stage.

Immune and metabolic alterations in first episode psychosis (FEP) patients.

The molecular underpinnings associated to first episode psychosis (FEP) remains to be elucidated, but compelling evidence supported an association of FEP with blood alterations in biomarkers related to immune system, growth factors and metabolism regulators. Many of these studies have not been already confirmed in larger samples or have not considered the FEP diagnostic subgroups. In order to identify biochemical signatures of FEP, the serum levels of the growth factors BDNF and VEGF, the immune regulators IL-1RA, IL-6, IL-10 and IL-17, RANTES/CCL5, MIP-1b/CCL4, IL-8 and the metabolic regulators C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin were analysed in 260 subjects collected in the GET UP project. The results indicated an increase of MIP-1b/CCL4, VEGF, IL-6 and PAI-1, while IL-17, ghrelin, glucagon and GLP-1 were decreased in the whole sample of FEP patients (p < 0.01 for all markers except for PAI-1 p < 0.05). No differences were evidenced for these markers among the diagnostic groups that constitute the FEP sample, whereas IL-8 is increased only in patients with a diagnosis of affective psychosis. The principal component analysis (PCA) and variable importance analysis (VIA) indicated that MIP-1b/CCL4, ghrelin, glucagon, VEGF and GLP-1 were the variables mostly altered in FEP patients. On the contrary, none of the analysed markers nor a combination of them can discriminate between FEP diagnostic subgroups. These data evidence a profile of immune and metabolic alterations in FEP patients, providing new information on the molecular mechanism associated to the psychosis onset for the development of preventive strategies and innovative treatment targets.

Altered expression of schizophrenia-related genes in mice lacking mGlu5 receptors.

The evidence underlying the so-called glutamatergic hypothesis ranges from NMDA receptor hypofunction to an imbalance between excitatory and inhibitory circuits in specific brain structures. Among all glutamatergic system components, metabotropic receptors play a main role in regulating neuronal excitability and synaptic plasticity. Here, we investigated, using qRT-PCR and western blot, consequences in the hippocampus and prefrontal/frontal cortex (PFC/FC) of mice with a genetic deletion of the metabotropic glutamate receptor 5 (mGlu5), addressing key components of the GABAergic and glutamatergic systems. We found that mGlu5 knockout (KO) mice showed a significant reduction of reelin, GAD65, GAD67 and parvalbumin mRNA levels, which is specific for the PFC/FC, and that is paralleled by a significant reduction of protein levels in male KO mice. We next analyzed the main NMDA and AMPA receptor subunits, namely GluN1, GluN2A, GluN2B and GluA1, and we found that mGlu5 deletion determined a significant reduction of their mRNA levels, also within the hippocampus, with differences between the two genders. Our data suggest that neurochemical abnormalities impinging the glutamatergic and GABAergic systems may be responsible for the behavioral phenotype associated with mGlu5 KO animals and point to the close interaction of these molecular players for the development of neuropsychiatric disorders such as schizophrenia. These data could contribute to a better understanding of the involvement of mGlu5 alterations in the molecular imbalance between excitation and inhibition underlying the emergence of a schizophrenic-like phenotype and to understand the potential of mGlu5 modulators in reversing the deficits characterizing the schizophrenic pathology.