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Alterations in cognitive performance have been described in patients with major depressive disorder (MDD). However, the specific risk factors of these changes are not yet known. This study aimed to explore whether inmunometabolic parameters are related to cognitive performance in MDD in comparison to healthy controls (HC) Methods: Sample consisted of 84 MDD patients and 78 HC. Both groups were compared on the results of cognitive performance measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), the presence of metabolic syndrome (MetS) and an inflammatory/oxidative index calculated by a principal component analysis of peripheral biomarkers (tumor necrosis factor, C-reactive protein and 4-hydroxynonenal). A multiple linear regression was carried out, to study the relationship between inmunometabolic variables and the global cognitive performance, being the latter the dependent variable. Results: Significant differences were obtained in the inflammatory/oxidative index between both groups (F(1157)= 12.93; p < .001), also in cognitive performance (F(1157)= 56.75; p < .001). The inmunometabolic covariate regression model (i.e., condition (HC/MDD), sex, age and medication loading, MetS, inflammatory/oxidative index and the interaction between MetS and inflammatory/oxidative index) was statistically significant (F(7157)= 11.24; p < .01) and explained 31% of variance. The condition, being either MDD or HD, (B=˗0.97; p < .001), age (B=˗0.28; p < .001) and the interaction between inflammatory/oxidative index and MetS (B=˗0.38; p = .02) were factors associated to cognitive performance. Limitations: Sample size was relatively small. The cross-sectional design of the study limits the possibilities of analysis. Conclusions: Our results provide evidence on the conjoint influence of metabolic and inflammatory dysregulation on cognitive dysfunction in MDD patients. In this way, our study opens a line of research in immunometabolic agents to deal with cognitive decline associated with MDD, This study was supported in part by grants from the Carlos III Health Institute through the Ministry of Science, Innovation and Universities (PI15/00662, PI15/0039, PI15/00204, PI19/01040), co-funded by the European Regional Development Fund (ERDF) “A way to build Europe”, CIBERSAM, and the Catalan Agency for the Management of University and Research Grants (AGAUR 2017 SGR 1247). We also thank CERCA Programme/ Generalitat de Catalunya for institutional support. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. MJP was funded with a Miguel Servet II contract until 2020 (CP16/00020) from the Carlos III Health Institute through the Spanish Ministry of Health. YSC work is supported by the FPI predoctoral grant (FPI 2016/17) from Universidad Autonoma de Madrid. The authors would like to acknowledge the support of the research participants, who helped to make this work possible. We thank Tamara Oliva and Marta Martín for technical assistance

Background Cognitive and negative symptoms are key determinants in schizophrenia functionality. Cognitive remediation (CR) has shown to improve cognition in patients with schizophrenia but the impact on functionality is still unsatisfactory. On the other hand, an improvement in negative symptoms has also been described with CR and some studies have shown physical exercise (PE) may also improve negative symptoms. The present study sets out to investigate the effects of CR+PE in overall negative symptoms, and more specifically, in the avolition and expression factor, as well as in functionality, in a sample of patients diagnosed with multi-episode schizophrenia. Furthermore, it sets out to investigate determinants of functionality at follow-up. Methods Randomized controlled trial with two groups: CR+PE and CR plus lifestyle promotion (LP) (control group) (www.clinicaltrials.gov NCT 02864576). Participants: Subjects fulfilling DSM-IV-TR criteria for schizophrenia or schizo-affective disorder diagnosis, aged between 25–60 years, with an illness duration >o = 10 years, clinically stable and with low physical activity were included. Each randomly assigned intervention consists of 36 sessions carried out 3-times/week in groups of 4–6 participants of CR+PE or CR+LP. Analyses: Baseline sociodemographic and clinical characteristics were assessed at baseline in both groups. Repeated measures of multiple analysis of variance (MANOVA) was performed for negative symptoms (BNSS total scale and avolition and expression factors) and functionality (GAF score) with group (CR+PE vs CR+LP) as the between-subject factor and time (pre-treatment and post-treatment) as the within-group factor. The main effects of time, group, and time × group were examined. Multiple regression analysis (whole sample) with GAF at follow-up as the dependent variable and avolition, expression and PANSS-P subscale at follow-up, and gender and age as independent variables was also carried out. Results 43 patients were included and randomized. 38 patients completed the study, 19 in each group. There were not statistically significant differences between both groups at baseline. There was a time x grup effect on GAF at follow-up (F=4.25 p= 0.047) and on the avolition factor (F=2.99 p= 0.09), with improvements in favour of the CR+ PE group. Furthermore, GAF at follow-up was only related with the avolition factor in the multiple regression analysis (B= -0.63, t -2.84, p=0.009 (CI -1.09-0.17)). Discussion CR+PE is associated with an improvement in negative symptoms, and more specifically, in the avolition factor, as well as in functionality. This specific improvement in the avolition factor is important, as functionality at follow-up is specifically associated with the avolition factor in our study, in accordance with previous studies. This work is funded by the Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación, with the Research Project PI15/00453.

Background Cognitive remediation (CR) is an evidence-based behavioral intervention for cognitive impairment in schizophrenia. Although the effectiveness of CR is well stablished, its effects are modest, especially in terms of functional outcome. There is an emerging literature suggesting that adding aerobic exercise to CR may exert synergistic effects. Despite these promising reports, the extent to which aerobic exercise in combination with CRT can improve cognitive and daily functioning in multiepisode schizophrenia and schizoaffective disorder remains unclear. Methods This is a single-blinded, randomized clinical trial (NCT02864576) with two different groups: 1) patients with multiepisode schizophrenia or schizoaffective disorder receiving 3-month Aerobic exercise plus CR treatment (three weekly sessions, 40min of Aerobic exercise and 90min of CR), and 2) patients with multiepisode schizophrenia or schizoaffective disorder receiving Healthy lifestyle promotion plus CR treatment (three weekly sessions, 40min of Healthy lifestyle promotion and 90min of CR). Primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) and the Global Assessment of Functioning (GAF), which were assessed (among others) at baseline and immediately after treatment. For the present work, the sample included in the analysis were 34 patients for whom cognitive data were available. Treatment effects on neurocognition and functional outcome were analyzed by applying the multivariate general linear model (GLM) repeated measures. Results After treatment, both groups exhibited a significant improvement in MCCB visual learning memory (F=14.298, p= 0.001), working memory (F=6.626, p= 0.015) and speed of processing (F=16.344, p= 0.001) domains. However, no significant benefits were evidenced for problem solving (F=2.143, p= 0.153), verbal learning memory (F= 0.321, p= 0.575) and attention/vigilance (F=0.740, p= 0.397) domains. Functional outcome, as measured by the GAF, was more improved in the Aerobic exercise plus CR group than in the Healthy lifestyle promotion plus CR group (F=4.248, p= 0.047). Discussion Our preliminary findings indicate that combining aerobic exercise with cognitive remediation may promote a large impact on functional outcome in patients with multiepisode schizophrenia or schizoaffective disorder.