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Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups—a ‘lower brain volume’ subgroup (SG1) and an ‘higher striatal volume’ subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership (‘None’), and mixed SG1 + SG2 subgroups (‘Mixed’). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of ‘lower brain volume’ in SG1 and ‘higher striatal volume’ (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36 months of age. Social interaction deficiencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difficult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and affect the expression of genes related to different neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in different body fluids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in different studies using the mean values. In addition, we summarized p values for differential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the meta-analysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are differentially expressed in various tissues and body fluids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fluid for miRNA measurements, because it is easy to collect from children compared to other biological fluids.

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.

PURPOSE: To determine clinical predictors associated with corticosteroid administration and its association with ICU mortality in critically ill patients with severe influenza pneumonia. METHODS: Secondary analysis of a prospective cohort study of critically ill patients with confirmed influenza pneumonia admitted to 148 ICUs in Spain between June 2009 and April 2014. Patients who received corticosteroid treatment for causes other than viral pneumonia (e.g., refractory septic shock and asthma or chronic obstructive pulmonary disease [COPD] exacerbation) were excluded. Patients with corticosteroid therapy were compared with those without corticosteroid therapy. We use a propensity score (PS) matching analysis to reduce confounding factors. The primary outcome was ICU mortality. Cox proportional hazards and competing risks analysis was performed to assess the impact of corticosteroids on ICU mortality. RESULTS: A total of 1846 patients with primary influenza pneumonia were enrolled. Corticosteroids were administered in 604 (32.7%) patients, with methylprednisolone the most frequently used corticosteroid (578/604 [95.7%]). The median daily dose was equivalent to 80 mg of methylprednisolone (IQR 60-120) for a median duration of 7 days (IQR 5-10). Asthma, COPD, hematological disease, and the need for mechanical ventilation were independently associated with corticosteroid use. Crude ICU mortality was higher in patients who received corticosteroids (27.5%) than in patients who did not receive corticosteroids (18.8%, p

[Introduction]: The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment. [Material and methods]: One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment. [Results]: After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment. [Conclusion]: We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia., The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005– 0308007; and Fundación Marqués de Valdecilla API07/011. Unrestricted educational and research grants from AstraZeneca, Pfizer, Bristol-Myers Squibb, and Johnson & Johnson provided support for PAFIP activities.

© The Author(s) 2019., Antipsychotic drugs are one of the largest types of prescribed drugs. However, antipsychotic-induced weight gain (AIWG) is a major problem for the patients. AIWG increases cardiovascular and cerebrovascular morbidity and mortality, and reduces quality of life and drug compliance. To characterize changes in gene expression related to AIWG, we sequenced total messenger RNA from the blood samples of two groups of schizophrenia patients before and after 3 months of treatment with antipsychotics. The “weight gain” group was defined by an increase of body mass index (BMI) >1.5 points (18 patients; median BMI increase = 2.69) and the “no weight gain” group was defined by a change of BMI between −1.0 points (18 patients; median BMI increase = 0.26). We found 115 genes with significant differential expression in the weight gain group before and after medication and 156 in the no weight gain group before and after medication. The weight gain group was significantly enriched with genes related to “obesity” and “BMI” (Fisher; p = 0.0002 and 0.01, respectively) according to the Gene Reference into Function (GeneRIF) database. In the no weight gain group, the enrichment was much smaller (Fisher; p = 0.02 and 0.79). This study is a first step toward detecting genetic factors that cause AIWG and to generating prediction tests in future studies with larger data sets., C.P. was supported by the PTA fellowship (PTA2015-10483-I) of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). B.C.-F. was supported by the Ministerio de Ciencia e Innovación (MICINN) in the coordinated project SAF2010- 20840-C02-01/02 and by MINECO (SAF2013-46292-R). J.S. was supported by MICINN (SAF2010-20840-C02-01) and by the NIH (5R01HD056465-07; sub-award #320793 from The Children’s Hospital of Philadelphia).

Relapses may represent a critical hazard in schizophrenia spectrum disorders as they are associated with an increased risk of a clinical and functional deterioration. Preventing relapse after recovering from a first psychotic episode has become a major challenge due to its critical impact on lifelong functionality. This study explored the rate of first and second relapses and the predictors associated with these relapses in a large cohort of non-affective psychosis patients during a period of 3 years after the first break of the illness. From February 2001 to May 2014, sociodemographic and clinical data from an epidemiological cohort of 341 non-affective first-episode psychosis patients at risk of relapse were analysed at a specialized early intervention service. Logistic regression, Cox regression, and Kaplan–Meier survival analyses were performed to compare non-relapsed and relapsed patients. One hundred and sixty-six (48.7%) individuals relapsed at least once. Median time to relapse was 17.0 months in non-adherent patients and 40.0 months in adherent patients (log-rankχ 2: 51.36; p

Schizophrenia is a debilitating psychiatric disorder and patients experience significant comorbidity, especially cognitive and psychosocial deficits, already at the onset of disease. Previous research suggests that treatment during the earlier stages of disease reduces disease burden, and that a longer time of untreated psychosis has a negative impact on treatment outcomes. A targeted literature review was conducted to gain insight into the definitions currently used to describe patients with a recent diagnosis of schizophrenia in the early course of disease (‘early’ schizophrenia). A total of 483 relevant English-language publications of clinical guidelines and studies were identified for inclusion after searches of MEDLINE, MEDLINE In-Process, relevant clinical trial databases and Google for records published between January 2005 and October 2015. The extracted data revealed a wide variety of terminology and definitions used to describe patients with ‘early’ or ‘recent-onset’ schizophrenia, with no apparent consensus. The most commonly used criteria to define patients with early schizophrenia included experience of their first episode of schizophrenia or disease duration of less than 1, 2 or 5 years. These varied definitions likely result in substantial disparities of patient populations between studies and variable population heterogeneity. Better agreement on the definition of early schizophrenia could aid interpretation and comparison of studies in this patient population and consensus on definitions should allow for better identification and management of schizophrenia patients in the early course of their disease.

Rationale: To enhance the effectiveness of antipsychotics in first-episode psychosis is crucial in order to achieve the most favourable prognosis. Difference in effectiveness between antipsychotics is still under debate. Objective: The purpose of this study is to determine the long-term (3-year) effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. Method: This is a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis. One hundred seventy-four patients were randomly assigned to haloperidol (N=56), olanzapine (N=55), or risperidone (N=63) and followed up for 3 years. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per-protocol populations was conducted in the analysis for clinical efficacy. Results: The treatment discontinuation rate for any cause differed significantly between treatment groups (χ 2=10.752; p=0.005), with a higher rate in haloperidol than in risperidone and olanzapine. The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance (χ 2=3.022; p=0.082). There was a significant difference in the mean time to all-cause discontinuation between groups (log-rank χ 2 =12.657;df=2; p=0.002). There were no significant advantages to any of the three treatments in reducing the psychopathology severity. Conclusions: After 3 years of treatment, a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics (SGAs). The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics. © 2011 Springer-Verlag., The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004, SENY Fundació Research Grant CI 2005–0308007 and Fundación Marqués de Valdecilla API07/011.

Negative symptoms of schizophrenia have been related to disturbances of executive functions, memory, attention and motor functioning. The executive functions dimension comprises a variety of cognitive subprocesses, including speed of processing, flexibility and working memory. We independently analysed the relationship between different cognitive tasks and clinical symptoms (negative, positive and disorganized) in a sample of 126 first-episode patients with schizophrenia spectrum disorders. Negative symptoms were significantly associated with performance on executive-functions and motor coordination tasks. Within the executive functions domain only those tests that required speeded performance showed a significant association with the negative dimension. The widely described relationship between negative symptoms and executive impairments in schizophrenia appears to be mediated by likely dysfunctions in the speed of processing instead of by working memory impairment.

Antipsychotic-induced weight gain is an important issue in the treatment of psychotic illnesses, and affects 80% of individuals being treated with antipsychotic drugs. However, the true dimension of weight gain and many accepted 'facts' in this area remain unclear as most research has been conducted in short-term trials and has included individuals receiving prolonged antipsychotic treatment. This review aims to systematically and critically review the evidence on weight gain induced by the two leading second-generation antipsychotics (olanzapine and risperidone) and the most widely researched first-generation antipsychotic (haloperidol) in patients with chronic and first-episode psychotic disorders. Weight gain was 3- to 4-fold greater in studies that included young patients with limited previous exposure to antipsychotic agents in both short-term studies (7.1-9.2 kg for olanzapine, 4.0-5.6 kg for risperidone and 2.6-3.8 kg for haloperidol vs 1.8-5.4 kg, 1.0-2.3 kg and 0.01-1.4 kg, respectively, in studies that included patients with chronic psychotic disorders) and long-term trials (10.2-15.4 kg for olanzapine, 6.6-8.9 kg for risperidone and 4.0-9.7 kg for haloperidol vs 2.0-6.2 kg, 0.4-3.9 kg and -0.7 to 0.4 kg, respectively). The same disparity was observed regarding the proportion of patients increasing their baseline weight by > or =7% (the cut-off for clinically significant weight gain). Recent studies carried out in young patients with first-episode psychosis (FEP), along with methodological artefacts in studies of chronic populations, suggest that the magnitude of weight gain reported by much of the literature could in fact be an underestimation of the true magnitude of this adverse effect. Although antipsychotics present idiosyncratic patterns of weight gain, they may also generate similar absolute gains.

The aim of this study was to examine possible cognitive changes throughout the early course of schizophrenia spectrum disorders.Forty-two patients, aged 15-50 years, admitted to a first episode psychosis program (PAFIP) serving to the community of Cantabria (Spain) and 43 healthy volunteers completed a brief battery of five neurocognitive tests at four time-points over 3 months. The cognitive testing comprise five domains: attention, visuomotor speed, declarative memory, working memory and executive function. Baseline assessment occurred within 72 hour after the initiation of standard pharmacological treatment, and after then parallel forms of the tests were applied at week-2, week-6, and month-3.Patient scores showed a significant impairment compared to healthy volunteers in the five cognitive domains at baseline and week-2 assessments. After the first 3 months of antipsychotic treatment, the patient group performance reached healthy volunteers level on executive function (Stroop interference) and immediate verbal memory tests. In contrast, performance on working memory, sustained attention, visuomotor speed, and verbal memory delayed recall domains still remained below healthy volunteers, although visuomotor processing speed showed a significant improvement.Schizophrenia spectrum patients show heterogeneous patterns and degrees of cognitive changes that contribute to stress the importance of when, what, and how neurocognitive functioning in the early phases of the illness is evaluated.

Background The Screen for Cognitive Impairment in Psychiatry (SCIP) is a simple and easy to administer scale developed for screening cognitive deficits. This study presents the diagnostic-specific standardization data for this scale in a sample of schizophrenia and bipolar I disorder patients. Methods Patients between 18 and 55 years who are in a stable phase of the disease, diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar I disorder were enrolled in this study. Results The SCIP-S was administered to 514 patients (57.9% male), divided into two age groups (18–39 and 40–55 years) and two educational level groups (less than and secondary or higher education). The performance of the patients on the SCIP-S is described and the transformed scores for each SCIP-S subtest, as well as the total score on the instrument, are presented as a percentile, z-score, T-scores, and IQ quotient. Conclusions We present the first jointly developed benchmarks for a cognitive screening test exploring functional psychosis (schizophrenia and bipolar disorder), which provide increased information about patient’s cognitive abilities. Having guidelines for interpreting SCIP-S scores represents a step forward in the clinical utility of this instrument and adds valuable information for its use.