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There are discrepancies about if the severity of the symptomatology in schizophrenia is related to neurocognitive performance, functional outcome, and quality of life (QoL). Also, there are controversial data about the comparison between euthymic bipolar patients and different subgroups of schizophrenia in neurocognition, functioning, and QoL level. The present study aimed to compare the neurocognitive performance, functional outcome, and QoL of remitted and non-remitted patients with SC with respect to a group of euthymic patients with BD, and a control group. It included 655 subjects: 98 patients with schizophrenia in remission (SC-R), 184 non-remitted patients with schizophrenia (SC-NR), 117 euthymic patients with bipolar I disorder (BD), and 256 healthy subjects. A comprehensive clinical, neurocognitive (six cognitive domains), functional, and QoL assessment was carried out. Remission criteria of Andreasen were used to classify schizophrenia patients as remitted or non-remitted. Compared with control subjects all groups of patients showed impaired neurocognitive performance, functioning and QoL. SC-R patients had an intermediate functioning between control subjects and SC-NR, all at a neurocognitive, functional, or QoL level. There were no significant differences between SC-R and BD. These results suggest that reaching clinical remission is essential to achieve a better level of psychosocial functioning, and QoL. Likewise, the results of this study suggest that euthymic patients with bipolar disorder and patients with schizophrenia in remission are comparable at the neurocognitive and functional levels, which might have implications in the pathophysiology of both disorders.

The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up.Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, aftergt;2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions.Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden.The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.

This study is part of a coordinated-multicentre Project, funded by the Ministerio deEconomia y Competitividad (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Car-los III–Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Eu-ropa, Centro de Investigacion Biomedica en Red de salud Mental, CIBERSAM, by theCERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca delDepartament d’Economia I Coneixement (2017SGR1355), Departament de Salut de laGeneralitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessio desubvencions del Pla Estrategic de Recerca i Innovacio en Salut (PERIS) 2016-2020,modalitat Projectes de recerca orientats a l’atencio primaria, amb el codi d’expedientSLT006/17/00345

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.

The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age- and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d>0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls.

Background Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. Methods A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. Results Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F = 13.45; p ≤0.001) and working memory domains (F = 4.30; p = 0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F = 19.60; p ≤0.001). No significant differences were revealed in the comparison between the patient groups. Conclusions This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.

Aims: This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. Methods: In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. Results: There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1 > Time 2 > Time 3); F(2,151) = 20.45, p < 0.001. Poorer premorbid adjustment (p = 0.01) and higher negative symptoms at baseline (p < 0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R-2 = 0.21, p < 0.001). Conclusions: We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome. (C) 2017 Elsevier B.V. All rights reserved.

A number of findings suggest that inflammation plays a role in the pathophysiology of schizophrenia. Taking into account a physiological balance between pro- and anti-inflammatory mediators, we measured the plasma levels of cyclooxygenase-derived mediators and other key pro- and anti-inflammatory transcription factors in peripheral blood mononuclear cells (PBMC). Forty healthy subjects and 46 treated chronic schizophrenic patients with an acutely exacerbated condition who met DSM-IV criteria were included. COX by-products prostaglandin E2 (PGE2) and 15d-prostaglandin J2 (15d-PGJ2) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPARγ) as well as nuclear factor kappaB (NFκB) activity in nuclear extracts from PBMC and expression of its inhibitory subunit IκBα in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE2 than age-matched controls (p=0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ2 were lower (p=0.004), correlating with a lower expression of its nuclear target, PPARγ in nuclear extracts from PBMC (p=0.001). Although no changes in NFκB activity were observed between patients and healthy controls, the expression of its inhibitory protein IκBα was lower in the patients compared to the controls (p=0.027). These findings suggest that schizophrenia is associated with a systemic imbalance in the plasma levels of pro-inflammatory/anti-inflammatory prostaglandins in favor of the former. Furthermore, the expression and activity of anti-inflammatory PPARγ are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients.

Cognitive function in schizophrenia has been associated with different sociodemographic and clinical variables. Substance use disorder (SUD) history has also been associated with cognition in schizophrenia; however, contradictory results have been found regarding its influence on cognitive function. Our aim was to study the relationship between executive function and a) age, b) duration of illness, c) number of psychotic episodes, d) positive symptoms, and e) negative symptoms, in a sample of schizophrenic patients, and secondly to study whether these relationships persisted after stratification of the sample according to the presence or absence of SUD history. A final sample of 203 schizophrenic patients were evaluated for psychotic symptoms using the PANSS, and assessed using a neuropsychological battery to calculate a composite executive function score. Linear regression analyses were performed, with this executive score as the dependent variable, and age, duration of illness, number of psychotic episodes, positive PANSS score and negative PANSS score as independent variables. For the total sample, the regression model showed three variables to be significant predictors of the executive score: age (p=0.004), number of episodes (p=0.027), and PANSS negative score (p=0.003). However, once the sample was stratified, the regression model showed age (p=0.011) and number of episodes (p=0.011) to be predictor variables for the executive score in the group of schizophrenic patients with SUD history, while age (p=0.028) and PANSS negative score (p=0.006) were predictors in the group of schizophrenic patients without such history. These findings highlight the importance of considering SUD history in studies of cognitive function in schizophrenia.

Patients with schizophrenia exhibit impairments in prepulse inhibition (PPI) of the startle response. Available data suggest that atypical antipsychotics may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, previous studies have used between-subjects rather than longitudinal within-subjects designs to demonstrate superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in patients with schizophrenia. This longitudinal within-subjects test-retest study was designed to evaluate changes in PPI and clinical symptoms in patients with schizophrenia after switching from the conventional antipsychotic zuclopenthixol to long-acting injectable risperidone. PPI was measured in 45 chronic male patients with schizophrenia treated with zuclophentixol depot (session T1), and 12 weeks after switching to long-acting injectable risperidone (session T2). Thirty-six healthy control subjects were also evaluated. Patients with schizophrenia showed a significant improvement in PPI after changing to long-acting risperidone. Improvement of PPI deficits between T1 and T2 assessments correlated significantly with improvements in PANSS general psychopathology subscale scores. Our findings indicate that long-acting risperidone improves PPI deficits in subjects with chronic schizophrenia. These results also suggest that the PPI-restoring effect of risperidone may be related to improvement in symptoms other than positive and negative symptoms.

Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps

Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p = 1.7 x 10(-4), Allelic odds ratio = 1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p < 0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis. (C) 2014 Published by Elsevier B. V.

Different exploratory and confirmatory factorial analyses of the Positive and Negative Syndrome Scale (PANSS) have found a number of factors other than the original positive, negative, and general psychopathology. Based on a review of previous studies and using confirmatory factor analyses (CFA), Wallwork et al. (Schizophr Res 2012; 137: 246–250) have recently proposed a consensus five-factor structure of the PANSS. This solution includes a cognitive factor which could be a useful measure of cognition in schizophrenia. Our objectives were 1) to study the psychometric properties (factorial structure and reliability) of this consensus five-factor model of the PANSS, and 2) to study the relationship between executive performance assessed using the Wisconsin Card Sorting Test (WCST) and the proposed PANSS consensus cognitive factor (composed by items P2-N5-G11). This cross-sectional study included a final sample of 201 Spanish outpatients diagnosed with schizophrenia. For our first objective, CFA was performed and Cronbach's alphas of the five factors were calculated; for the second objective, sequential linear regression analyses were used. The results of the CFA showed acceptable fit indices (NNFI = 0.94, CFI = 0.95, RMSEA = 0.08). Cronbach's alphas of the five factors were adequate. Regression analyses showed that this five-factor model of the PANSS explained more of the WCST variance than the classical three-factor model. Moreover, higher cognitive factor scores were associated with worse WCST performance. These results supporting its factorial structure and reliability provide robustness to this consensus PANSS five-factor model, and indicate some usefulness of the cognitive factor in the clinical assessment of schizophrenic patients.