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Background: There is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent., Method: In this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables., Results: Adjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p < 0.001). The association between suPAR and CDSS score was significant in females (p < 0.001) but not in males. Immune activation measured by hsCRP was not associated with depressive symptoms after adjusting for BMI., Conclusion: Our findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms., (© 2021. The Author(s).)

There is a need for treatments targeting neurocognitive dysfunctions in schizophrenia. The aim of this study was to investigate the neurocognitive effect of aerobic high-intensity interval training (HIIT). A comparison group performed sport simulating active video gaming (AVG). We anticipated that HIIT would improve neurocognition beyond any effect of AVG, due to engagement in higher intensity cardiorespiratory demands. Recent research on the beneficial neurocognitive effect of AVG challenges this expectation but added new relevance to comparing the two interventions. This is an observer-blinded randomized controlled trial. Eighty-two outpatients diagnosed with schizophrenia were allocated to HIIT (n = 43) or AVG (n = 39). Both groups received two supervised sessions per week for 12 weeks. The attrition rate was 31%, and 65% of the participants were defined as protocol compliant study completers. Intention-to-treat analyses showed significant improvements in the neurocognitive composite score from baseline to post-intervention and from baseline to 4 months follow-up in the total sample. The same pattern of results was found in several subdomains. Contrary to our hypothesis, we found no interaction effects of time and group, indicating equal effects in both groups. Separate within-group analysis unexpectedly showed trends of differential effects in the learning domain, as HIIT showed post-intervention improvement in verbal but not visual learning, while AVG showed improvement in visual but not verbal learning. HIIT and AVG improve neurocognition equally, suggesting that both interventions may be applied to target neurocognition in schizophrenia. Future research should investigate trends towards possible differential effects of exercise modes on neurocognitive subdomains. NCT02205684, 31.07.14.

Background: Exercise may improve cardiorespiratory fitness in people with schizophrenia, however, possible condition-specific cardiorespiratory disadvantages, a scarcity of methodologically sound studies, and conflicting results raise questions about the effect of exercise on maximal oxygen uptake (VO 2max ) in this group. The primary aim of this study, therefore, was to investigate the effect of high-intensity interval training on VO 2max in people with schizophrenia. Second, we sought to determine whether the intervention would have an effect on general physical activity (PA) level and body composition., Methods: Eighty-two patients with schizophrenia were randomly assigned to supervised high-intensity interval training or computer gaming skills training, performed twice a week for 12 weeks. Oxygen uptake was measured directly, during a maximum exercise session on a treadmill. PA level were assessed using ActiGraph accelerometer, and body composition was assessed by bioelectrical impedance. Differences between groups were assessed by analysis of variance using a univariate general linear model., Results: There were no significant differences between the groups on any of the cardiorespiratory variables neither at baseline nor after the program. There were also no significant within-group differences in any of the cardiorespiratory fitness variables between the baseline and post-program time points, despite that 61% of the participants performing high-intensity interval training showed a significant increase in workload on the treadmill. However, 47% of the participants in the high-intensity interval training group had a ≥ 5% increase in VO 2max . Participants supervised by mental health care providers with PA competence (e.g. rehabilitation center staff, sport scientist, physical trainer) had a much larger increase in VO 2max compared to participants supervised by mental health workers without such competence, and when adding PA competence to the model, the intervention group increased VO 2max significantly compared to the comparison group. The intervention had no significant effect on PA level or body composition., Conclusions: The intervention did not improve VO 2max , PA level or body composition but succeeded in increasing workload on the treadmill. With regard to VO 2max , approximately half of the patients may be considered responders., Trial Registration: ClinicalTrials.gov ; NCT02205684 , registered July 2014.

Objective: We investigated whether the relationship between cardio-respiratory fitness (CRF) and cognition in schizophrenia is general, or due to selective relationships between CRF and specific aspects of cognitive function., Method: Eighty outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale version 4 General Ability Index (WAIS GAI), the MATRICS Consensus Cognitive Battery (MCCB) and the Emotion in Biological Motion (EBM) test. CRF was assessed with peak oxygen uptake measured directly during maximum exercise using a modified Balke protocol. Partial correlations, controlling for sex and age, were obtained for the perceptual and the verbal indices of WAIS GAI, six cognitive domains of MCCB, and the EBM total score. A factor analysis was conducted on all 15 subtests of the WAIS GAI and the MCCB, and the factors were subjected to separate regression analyses with CRF as predictor., Results: Significant, moderately sized correlations were found between CRF and all cognitive domains except processing speed. The correlation appeared strongest for CRF and the Verbal Comprehension Index of WAIS GAI (r = 0.29, p = .005). The factor analysis identified three factors: one speed/attention/executive function factor, one verbal factor, and one perceptual factor. Regression analyses showed that VO 2peak explained a significant amount of variance in the verbal factor only (R 2  = 0.06, β = 0.329, p = .03)., Conclusion: The results indicate that the relationship between CRF and cognition in schizophrenia is selectively tied to a modality-specific association with verbal cognitive abilities. These findings have implications for understanding the relation between cognitive factors and physical health in schizophrenia. ClinicalTrials.gov reg. number NCT02205684 (clinicaltrials.gov/ct2/show/NCT02205684)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Although considered a promising design for testing social cognition, it is not clear to what extent the EmoBio test of emotion recognition actually predicts community functioning. It is also not clear whether the test measures something unique or different from nonsocial cognition. The present study tests whether EmoBio accounts for GAF function score and two operationalised community outcome measures. The study also analyses cognitive predictors of EmoBio performance, testing whether stimulus modality affects prediction., Methods: Eighty-three patients with schizophrenia were tested with EmoBio, the cognitive battery MCCB and WAIS-IV., Results: EmoBio accounted for a significant portion of variance in all three outcome measures. Only EmoBio predicted Lifetime Relationship status, and EmoBio remained a significant predictor of Independent living beyond non-social cognition. All cognitive measures contributed significantly to the variance in EmoBio, but entered together explained only a third of total variance., Conclusion: The study shows that emotion recognition accounts for community outcome. There was no clear effect of test-modality in predicting EmoBio performance, indicating no method invariance problem with EmoBio. It also indicates that the mechanisms underlying impaired social cognition in schizophrenia are different from the hypothesised non-verbal learning deficits in the disorder.

Objective: Thorough description of objectively assessed physical activity (PA) and sedentary time in people with schizophrenia is lacking, and previous studies comparing PA and cardiorespiratory fitness levels with healthy controls are limited by their small sample size and/or poor methodology., Method: PA, sedentary behavior, and cardiorespiratory fitness level were assessed in 67 adults diagnosed with schizophrenia (EPHAPS study) and compared with a population-based sample of 2809 adults (NPASS study)., Results: Fifty-five percent of the participants with schizophrenia had the unhealthy combination of not meeting the PA recommendations and sitting >7.5 h per day compared to 32% in the population-based sample. The PA level was especially low on weekday afternoons and evenings and throughout most of the day on weekends. The peak oxygen uptake for EPHAPS women was on average 23% lower than that for NPASS women, while EPHAPS men achieved on average 34% lower oxygen uptake on the exercise test compared with NPASS men., Conclusion: People with schizophrenia are significantly less physically active, more sedentary, and have a poorer cardiorespiratory fitness level compared with the general population. Tailor-made PA interventions for people with schizophrenia should target their PA and sedentary behavior on afternoons and weekends especially., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Schizophrenia is associated with reduced cardio-respiratory fitness (CRF), and impaired cognition is a core feature of the disorder. Despite their particular significance to schizophrenia disparately, the relationship between these two variables has not yet been thoroughly assessed. In this study we aimed to investigate naturally occurring associations between CRF and all cognitive domains within this patient population., Method: Eighty outpatients with schizophrenia spectrum disorders participated in the study. Neurocognition was assessed with the Wechsler Adult Intelligence Scale version 4 General Ability Index (WAIS GAI) and the MATRICS Consensus Cognitive Battery (MCCB). Oxygen uptake was measured directly by analyzing O 2 and CO 2 content in expired air during a maximum exercise session on a treadmill using a modified Balke protocol. Clinical symptom load was assessed with the Positive and Negative Syndrome Scale (PANSS). Hierarchical multiple regression analyses were conducted, controlling for sex and age, and negative psychotic symptom levels., Results: CRF explained a significant 8.2% and 9.1% of the variance in general intellectual ability and state-sensitive cognitive functioning respectively, beyond the impact of negative psychotic symptom load., Conclusion: The study indicates a direct relation between CRF and cognition in schizophrenia. Impaired cognition is a difficult-to-treat expression of the disorder, and identifying modifiable factors possibly mediating cognition, such as CRF, is of great clinical value., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Category fluency is associated with speed-, executive- and semantic impairments in schizphrenia. It has traditionally been linked to negative symptoms, whereas the relation to positive symptoms is mixed. Associations to the consensus negative, positive and disorganisation factors have not been analysed before., Methods: Animal fluency was administered to 81 patients with schizophrenia. Measures of overall performance and applied strategies were analysed in relation to the Wallwork five-factor PANSS-model., Results: Negative and disorganisation symptoms were negatively related to overall fluency performance. Positive symptoms were positively related to overall performance when controlling for disorganisation symptoms. Negative symptoms were related to fewer switches, less repetitions, less single animals intrusions, and both less rare and common animals. Positive symptoms were related to more effective retrieval of sub-category exemplars following a sub-category title, whereas there were no relation between symptoms and exemplars when the title was not retrieved. The Beta values of negative and positive symptoms were opposite., Conclusion: This is the first study showing that positive symptoms are related to increased fluency performance when disorganisation is controlled for. Like previous studies, negative symptoms were found to depress fluency. Strategy measures indicated that negative symptoms predispose for rigidity, whereas positive symptoms facilitate more efficient associative pathways.