Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. METHODS: Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. RESULTS: The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CONCLUSIONS: CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

Ten-year course of cognition in first-episode non-affective psychosis patients: PAFIP cohort.

BACKGROUND: A large body of research states that cognitive impairment in schizophrenia is static. Nevertheless, most previous studies lack a control group or have small study samples or short follow-up periods. METHOD: We aimed to address these limitations by studying a large epidemiological cohort of patients with first-episode schizophrenia spectrum disorders and a comparable control sample for a 10-year period. RESULTS: Our results support the generalized stability of cognitive functions in schizophrenia spectrum disorders considering the entire group. However, the existence of a subgroup of patients characterized by deteriorating cognition and worse long-term clinical outcomes must be noted. Nevertheless, it was not possible to identify concomitant factors or predictors of deterioration (all Ps > 0.05). CONCLUSIONS: Cognitive functions in schizophrenia spectrum disorder are stable; however, a subgroup of subjects that deteriorate can be characterized.

Peripheral lymphocyte signaling pathway deficiencies predict treatment response in first-onset drug-naïve schizophrenia.

Despite being a major cause of disability worldwide, the pathophysiology of schizophrenia and molecular basis of treatment response heterogeneity continue to be unresolved. Recent evidence suggests that multiple aspects of pathophysiology, including genetic risk factors, converge on key cell signaling pathways and that exploration of peripheral blood cells might represent a practical window into cell signaling alterations in the disease state. We employed multiplexed phospho-specific flow cytometry to examine cell signaling epitope expression in peripheral blood mononuclear cell (PBMC) subtypes in drug-naïve schizophrenia patients (n = 49) relative to controls (n = 61) and relate these changes to serum immune response proteins, schizophrenia polygenic risk scores and clinical effects of treatment, including drug response and side effects, over the longitudinal course of antipsychotic treatment. This revealed both previously characterized (Akt1) and novel cell signaling epitopes (IRF-7 (pS477/pS479), CrkL (pY207), Stat3 (pS727), Stat3 (pY705) and Stat5 (pY694)) across PBMC subtypes which were associated with schizophrenia at disease onset, and correlated with type I interferon-related serum molecules CD40 and CXCL11. Alterations in Akt1 and IRF-7 (pS477/pS479) were additionally associated with polygenic risk of schizophrenia. Finally, changes in Akt1, IRF-7 (pS477/pS479) and Stat3 (pS727) predicted development of metabolic and cardiovascular side effects following antipsychotic treatment, while IRF-7 (pS477/pS479) and Stat3 (pS727) predicted early improvements in general psychopathology scores measured using the Brief Psychiatric Rating Scale (BPRS). These findings suggest that peripheral blood cells can provide an accessible surrogate model for intracellular signaling alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic and cardiovascular side effects following antipsychotic therapy.

Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.

BACKGROUND: The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. METHOD: A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. RESULTS: The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. CONCLUSIONS: The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum.

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy.

Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks.

Neuropsychiatric disorders overlap in symptoms and share genetic risk factors, challenging their current classification into distinct diagnostic categories. Novel cross-disorder approaches are needed to improve our understanding of the heterogeneous nature of neuropsychiatric diseases and overcome existing bottlenecks in their diagnosis and treatment. Here we employ high-content multi-parameter phospho-specific flow cytometry, fluorescent cell barcoding and automated sample preparation to characterize ex vivo signaling network responses (n = 1764) measured at the single-cell level in B and T lymphocytes across patients diagnosed with four major neuropsychiatric disorders: autism spectrum condition (ASC), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ; n = 25 each), alongside matched healthy controls (n = 100). We identified 25 nodes (individual cell subtype-epitope-ligand combinations) significantly altered relative to the control group, with variable overlap between different neuropsychiatric diseases and heterogeneously expressed at the level of each individual patient. Reconstruction of the diagnostic categories from the altered nodes revealed an overlapping neuropsychiatric spectrum extending from MDD on one end, through BD and SCZ, to ASC on the other end. Network analysis showed that although the pathway structure of the epitopes was broadly preserved across the clinical groups, there were multiple discrete alterations in network connectivity, such as disconnections within the antigen/integrin receptor pathway and increased negative regulation within the Akt1 pathway in CD4+ T cells from ASC and SCZ patients, in addition to increased correlation of Stat1 (pY701) and Stat5 (pY694) responses in B cells from BD and MDD patients. Our results support the "dimensional" approach to neuropsychiatric disease classification and suggest potential novel drug targets along the neuropsychiatric spectrum.

Predictors of diagnostic stability in brief psychotic disorders: Findings from a 3-year longitudinal study.

INTRODUCTION: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. METHODS: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria was explored in a large epidemiological cohort (n = 569) of non-affective first-episode psychosis (FEP) patients enrolled in a three-year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. RESULTS: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM-IV criteria for BPD, of whom 40 completed the three-year follow-up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. CONCLUSION: Our findings confirm that BPD is a clinical condition with moderate-to-low temporal stability and demonstrate that approximately two-thirds of FEP individuals experiencing BPD will develop a long-lasting psychotic disorder during follow-up, mainly schizophrenia.

Stability of schizophrenia diagnosis in a 10-year longitudinal study on first episode of non-affective psychosis: Conclusions from the PAFIP cohort.

OBJECTIVE: To evaluate the 10-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. METHODS: Changes in diagnosis of 209 FEP patients were described during 10 years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. RESULTS: Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the 10-year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. CONCLUSIONS: Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years.

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.

BACKGROUND: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. CONCLUSIONS: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

Progressive Structural Brain Changes and NRG1 Gene Variants in First-Episode Nonaffective Psychosis.

BACKGROUND: Structural brain abnormalities are already present during the early phases of psychosis, but factors underlying brain volume changes are still not well understood. The neuregulin 1 gene (NRG1), influencing neurodevelopment and neuroplasticity, has been associated with schizophrenia. Our aim was to examine whether variations in the NRG1 gene (SNP8NRG221132, SNP8NRG6221533 and SNP8NRG243177 polymorphisms) influence longitudinal changes in the brain during a first episode of psychosis (FEP). METHODS: A 3-year follow-up magnetic resonance imaging (MRI) study was performed. Fifty-nine minimally medicated patients who were experiencing FEP and 14 healthy control individuals underwent genotyping and structural brain MRI at baseline and at 1- and 3-year follow-up. A comparison of brain volumes, gray matter, white matter (WM), lateral ventricles (LV), cortical cerebrospinal fluid, and thalamus and caudate was made between the groups according to their genotype. RESULTS: In patients, the SNP8NRG6221533 risk C allele was significantly associated with increased LV volume across time. C allele carriers had significantly less WM compared with subjects homozygous for the T allele after the follow-up. No other significant differences were observed among subgroups. No significant changes according to the genotypes were found in healthy individuals. CONCLUSION: Our findings suggest that variations of neurodevelopment-related genes, such as the NRG1 gene, can contribute to brain abnormalities described in early phases of schizophrenia and progressive changes during the initial years of the illness. To our knowledge, it is the first time that a relation between NRG1 polymorphisms and longitudinal brain changes is reported. © 2015 S. Karger AG, Basel.

Immune system: a possible nexus between cannabinoids and psychosis.

BACKGROUND: Endocannabinoid system is involved in the regulation of the brain-immune axis. Cannabis consumption is related with the development, course, and severity of psychosis. The epidemiological evidence for increased occurrence of immunological alterations in patients with psychosis has not been sufficiently addressed. The aim of this review is to establish whether there is any scientific evidence of the influence of cannabinoids on aspects of immunity that affect susceptibility to psychotic disorder induction. METHODS: A comprehensive search of PubMed/MEDLINE, EMBASE and ISI Web of Knowledge was performed using combinations of key terms distributed into three blocks: "immune", "cannabinoid", and "endocannabinoid receptor". Studies were considered to be eligible for the review if they were original articles, they reported a quantitative or qualitative relation between cannabinoid ligands, their receptors, and immune system, and they were carried out in vitro or in mammals, included humans. All the information was systematically extracted and evaluated. RESULTS: We identified 122 articles from 446 references. Overall, endocannabinoids enhanced immune response, whereas exogenous cannabinoids had immunosuppressant effects. A general change in the immune response from Th1 to Th2 was also demonstrated for cannabinoid action. Endogenous and synthetic cannabinoids also modulated microglia function and neurotransmitter secretion. CONCLUSION: The actions of cannabinoids through the immune system are quite regular and predictable in the peripheral but remain fuzzy in the central nervous system. Despite this uncertainty, it may be hypothesized that exposure to exocannabinoids, in particular during adolescence might prompt immunological dysfunctions that potentially cause a latent vulnerability to psychosis. Further investigations are warranted to clarify the relationship between the immunological effects of cannabis and psychosis.

Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies.

BACKGROUND: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ). METHOD: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. RESULTS: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ). CONCLUSION: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.

Lifestyle intervention based on exercise and behavioural counselling and its effect on physical and psychological health in outpatients with schizophrenia spectrum disorders. An exploratory, pragmatic randomized clinical trial.

Patients with Schizophrenia Spectrum Disorders (SSD) often lead unhealthy lifestyles. This pragmatic trial evaluated the effectiveness of a lifestyle intervention, consisting of a 12-week aerobic exercise program and behavioural counselling, in SSD outpatients with metabolic syndrome (MetS). It also aimed to assess persistence of potential effects in a 24-month long-term follow-up. Effectiveness was measured in terms of a wide range of outcomes involving physical and psychological health, quality of life, physical activity and changes in motivation to exercise within the context of the self-determination theory. Our primary outcome was waist circumference change. Thirty-three out of 48 participants completed the study. No differences between groups were found in terms of BMI change or other metabolic parameters. However, the active group (AG) showed improvement regarding waist circumference, negative symptomatology and identified motivation to exercise during the study and follow-up. The AG exhibited changes toward a more active pattern of activity after intervention. Moreover, belonging to the AG was a significant predictor for achieving any degree of clinical improvement after 24-month follow-up. Combined interventions of exercise and behavioural counselling in SSD patients with MetS should be considered as an essential part of the integral treatment in the context of mental health services.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

Increased risk of early lung function alterations in people with psychosis: A cross-sectional case-control study.

BACKGROUND: Tobacco smoking has been described as the main cause of chronic obstructive pulmonary disease (COPD) and this habit is clearly more frequent among individuals with psychosis than in the general population, with rates reaching up to 60%. However, little attention has been focused on the association of COPD and psychosis. We aimed to explore the risk of presenting early lung function alterations in a group of individuals with psychosis. METHODS: Following an observational cross-sectional design we studied a cohort of individuals with established psychosis (N=128), and compared them with a sex, age, and smoking habit matched control group (N=79). We evaluated respiratory symptoms by means of mMRC, CAT and Dyspnea-12 scales. And lung function through spirometry tests. RESULTS: Individuals with psychosis presented more respiratory symptoms than controls. Similarly, we observed significant differences in the lung function tests between these two groups, where individuals with psychosis presented worse results in most of the spirometry mean values (FEV1 or forced expiratory volume in the first one second: 3.29L vs. 3.75L, p<0.001; forced vital capacity or FVC: 4.25L vs. 4.72L, p=0.002; and FEV1/FVC ratio: 0.78 vs. 0.80, p=0.052). Patients also presented worse values of lung diffusion, with lower diffusing capacity for carbon monoxide (DLCO) than controls (6.95 vs. 8.54mmol/min/kPa, p<0.001). CONCLUSIONS: The individuals with psychosis in our study presented greater respiratory symptoms and poorer lung function measured through spirometry. These signs have been described as early signs of COPD.

Comparison of Mathematics Problem-Solving Abilities in Autistic and Non-autistic Children: the Influence of Cognitive Profile.

This study examines relationships between mathematical problem-solving performance (in terms of strategies used and accuracy) and the main cognitive domains associated with mathematical learning (i.e. executive functions, verbal comprehension and social perception) of children with and without autism spectrum disorder (ASD and non-ASD resp.). The study involved 26 ASD and 26 non-ASD children without intellectual disabilities, between 6 and 12 years old, matched by sex, age and school (grade and classroom). The results show a higher percentage of ASD children with problem solving difficulties than non-ASD (57% vs. 23% resp.). Poor performing ASD children showed comparatively lower scores in inhibition, theory of mind and verbal comprehension. Implications for the design of mathematical interventions for ASD students are discussed.

Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers.

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n = 26) and recent-onset schizophrenia patients (n = 36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F = 10.75, P = 0.002, Q = 0.024 and F = 21.58, P = 2.8 × 10-5, Q = 0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F = 21.46, P = 2.9 × 10-5, Q = 0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66-0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n = 34) from healthy controls (n = 39) with an AUC of 0.75 (95% CI: 0.64-0.86), and also differentiated schizophrenia patients (n = 22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n = 68), with an AUC of 0.83 (95% CI: 0.75-0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia.

In- and outpatient lifestyle interventions on diet and exercise and their effect on physical and psychological health: a systematic review and meta-analysis of randomised controlled trials in patients with schizophrenia spectrum disorders and first episode of psychosis.

Patients with non-affective psychosis often lead unhealthy lifestyles. We performed a systematic review and meta-analysis on non-pharmacological RCTs for improvement of diet and physical activity in non-affective psychosis patients, including first-episode psychosis. A variety of outcomes was analysed, including metabolic, psychopathology, cognitive, functional and quality of life outcomes. Fifty-nine studies were included. An improvement in anthropometric measurements (BMI, weight, waist circumference) was observed post-intervention, persisting after follow-up. Post-intervention benefit was found also for psychotic symptoms severity (also persisting after follow-up), many cognitive domains and physical and global functioning and quality of life. Conversely, no effect was observed in relation to most blood metabolites, blood pressure and non-psychotic psychopathology and spontaneous physical activity. Improvement was generally larger for interventions including exercise, especially moderate/vigorous aerobic exercise, but follow-up maintenance was greater for psychotherapy interventions. Sensitivity analyses limited to chronic stages of psychosis and low risk of bias studies produced comparable results. Further studies are needed to design optimized interventions in this vulnerable population.

Different neurocognitive profiles of risperidone and aripiprazole in the FIRST episode of psychosis: A 3-year follow-up comparison.

Cognitive deficits have been recognized as a central feature of schizophrenia spectrum disorders. These deficits are often related to more severe negative symptoms, as well as a poorer adjustment in social functioning. Therefore, it is important to improve cognitive performance from the onset of the disease. In this study, we compared the effects of two atypical antipsychotics, risperidone and aripiprazole, on cognition. The data used in the present investigation were obtained from a large epidemiological cohort of patients with a first episode of psychosis who were treated in a longitudinal intervention programme. The patients included in the program were randomized to treatment with risperidone or aripiprazole and were assessed for cognitive function at baseline and 3 years later. The final sample consisted of 115 patients, 55 of whom were initially assigned to risperidone and 60 to aripiprazole. The groups did not show significant differences in their sociodemographic or clinical characteristics at intake. Longitudinal analyses showed that risperidone-treated patients improved in the processing speed domain at the 3-year follow-up, while the aripiprazole group showed better scores for the executive function domain. Our study shows slight differences between the effects of risperidone and aripiprazole on cognition, suggesting different patterns of efficacy on cognitive function that may warrant more thorough research to determine the beneficial effects of these drugs on cognition. Future studies should evaluate the effects of these treatments over longer follow-up periods using standardized tools for the assessment of cognitive function.