As We Were and as We Should Be, Combined Exercise Training in Adults with Schizophrenia: CORTEX-SP Study Part I.

INTRODUCTION: Given the health benefits and the role of exercise as an anti-inflammatory adjuvant program, this study aimed to determine the effectiveness of a combined exercise program on cardiorespiratory fitness (CRF), body composition, and biochemical levels in adults with schizophrenia (SZ) characterized at baseline as metabolically unhealthy overweight with low CRF. METHODS: Participants diagnosed with SZ ( n = 112, 41.3 ± 10.4 yr, 28.7% women) were randomly assigned into a treatment-as-usual control group ( n = 53) or a supervised exercise group ( n = 59, 3 d·wk -1 ). Each combined exercise session consisted of both a low-volume high-intensity interval training (<10 min of high-intensity time per session) and a resistance circuit-training program. All variables were assessed before and after the intervention (20 wk). For the assessment of CRF, a peak cardiopulmonary exercise test on a cycle ergometer was used. RESULTS: After the intervention, participants from the exercise group ( n = 51) showed increases in CRF ( P < 0.001) through peak oxygen uptake (L·min -1 ; Δ = 17.6%; mL·kg -1 ·min -1 , Δ = 19.6%) and the metabolic equivalent of task (Δ = 19%), with no significant changes ( P > 0.05) in body composition and biochemical variables. However, the treatment-as-usual group ( n = 38) did not show any significant change in the study variables ( P > 0.05). Between-group significant differences ( P ≤ 0.05) were observed in CRF, first ventilatory threshold, and heart rate peak after the intervention period, favoring the exercise group. CONCLUSIONS: This study demonstrated that a supervised combined exercise program in people with SZ helps to maintain body composition values and improve CRF levels. This could lead to an important clinical change in the characterization from metabolically unhealthy overweight to a metabolically healthy overweight population. Hence, exercise should be considered a co-adjuvant program in the treatment of the SZ population.

Moderators of functional improvement after integrative cognitive remediation in schizophrenia: Toward a personalized treatment approach.

Cognitive remediation is an effective intervention for improving functional outcome in schizophrenia. However, the factors that moderate this improvement are still poorly understood. The study aimed to identify moderators of functional outcome improvement after integrative cognitive remediation (REHACOP) in schizophrenia. This was a secondary analysis of data from two randomized controlled trials, which included 182 patients (REHACOP group=94; active control group=88). Hierarchical regression analyses were conducted to identify moderators of functional outcome improvement. Two baseline level groups (low-level and high-level) were created to analyze the moderating role of this baseline level cluster using repeated measures ANCOVA. The REHACOP was effective regardless of participants' baseline level, but regression analyses indicated that the effectiveness on functional outcome was higher among those who were older, had fewer years in education, lower scores in baseline cognition and functional outcome, and more negative symptoms. Repeated measures ANOVA showed that the baseline level cluster influenced the improvement in functional outcome, with the low-level group showing greater improvements. The results reinforced the need to implement cognitive remediation programs more broadly as a treatment for schizophrenia in healthcare services. Furthermore, they provided evidence for the development of personalized cognitive remediation plans to improve benefits in different schizophrenia profiles.

'It Helped Me to Disconnect My Mind from the Problems': The Subjective Experiences of People with Schizophrenia Taking Part in a Concurrent Exercise Program.

The aim of this study was to investigate the subjective experiences of a concurrent exercise program designed to improve both physical and mental health, through participation, for people with schizophrenia. Participants diagnosed with schizophrenia (n = 35, 41.6 ± 10.3 years) received an intensive concurrent exercise program for a 5-month duration, three times a week, at out-of-hospital facilities. Qualitative data was collected via individual, semi-structured interviews, organized, and analyzed with thematic analysis. The findings highlight the participants' perspective in supporting an out-of-hospital exercise program as an acceptable and beneficial adjunct to usual treatment in people with schizophrenia for holistic health improvements.

Analyzing structural and functional brain changes related to an integrative cognitive remediation program for schizophrenia: A randomized controlled trial.

Cognitive remediation has been shown to improve cognition in schizophrenia, but little is known about the specific functional and structural brain changes related to the implementation of an integrative cognitive remediation program. This study analyzed the functional and structural brain changes identified after implementing an integrative cognitive remediation program, REHACOP, in schizophrenia. The program combined cognitive remediation, social cognitive training, and functional and social skills training. The sample included 59 patients that were assigned to either the REHACOP group or an active control group for 20 weeks. In addition to a clinical and neuropsychological assessment, T1-weighted, diffusion-weighted and functional magnetic resonance images were acquired during a resting-state and during a memory paradigm, both at baseline and follow-up. Voxel-based morphometry, tract-based spatial statistics, resting-state functional connectivity, and brain activation analyses during the memory paradigm were performed. Brain changes were assessed with a 2 × 2 repeated-measure analysis of covariance for group x time interaction. Intragroup paired t-tests were also carried out. Repeated-measure analyses revealed improvements in cognition and functional outcome, but no significant brain changes associated with the integrative cognitive remediation program. Intragroup analyses showed greater gray matter volume and cortical thickness in right temporal regions at post-treatment in the REHACOP group. The absence of significant brain-level results associated with cognitive remediation may be partly due to the small sample size, which limited the statistical power of the study. Therefore, further research is needed to clarify whether the temporal lobe may be a key area involved in cognitive improvements following cognitive remediation.

Cross-Validation of Predictive Equation for Cardiorespiratory Fitness by Modified Shuttle Walk Test in Adults with Schizophrenia: A Secondary Analysis of the CORTEX-SP Study.

Cardiorespiratory fitness (CRF) can be direct or estimated from different field tests. The Modified Shuttle Walk Test (MSWT) is suitable for all levels of function, allowing a peak response to be elicited. Therefore, we aimed (1) to validate the equation presented in the original study by Singh et al. for evaluating the relationship between MSWT with peak oxygen uptake (VO2peak) in adults with schizophrenia (SZ), (2) to develop a new equation for the MSWT to predict VO2peak, and (3) to validate the new equation. Participants (N = 144, 41.3 ± 10.2 years old) with SZ performed a direct measurement of VO2peak through a cardiopulmonary exercise test and the MSWT. A new equation incorporating resting heart rate, body mass index, and distance from MSWT (R2 = 0.617; adjusted R2 = 0.60; p < 0.001) performs better than the Singh et al. equation (R2 = 0.57; adjusted R2 = 0.57; p < 0.001) to estimate VO2peak for the studied population. The posteriori cross-validation method confirmed the model's stability (R2 = 0.617 vs. 0.626). The findings of the current study support the validity of the new regression equation incorporating resting heart rate, body mass index, and distance from MSWT to predict VO2peak for assessment of CRF in people with SZ.

Cognitive, creative, functional, and clinical symptom improvements in schizophrenia after an integrative cognitive remediation program: a randomized controlled trial.

This study analyzed the effectiveness of an integrative cognitive remediation program (REHACOP) in improving neurocognition, social cognition, creativity, functional outcome, and clinical symptoms in patients with schizophrenia. In addition, possible mediators predicting improvement in functional outcomes were explored. The program combined cognitive remediation with social cognitive training and social and functional skill training over 20 weeks. The sample included 94 patients, 47 in the REHACOP group and 47 in the active control group (occupational activities). Significant differences were found between the two groups in change scores of processing speed, working memory, verbal memory (VM), inhibition, theory of mind, emotion processing (EP), figural creative strengths, functional competence, disorganization, excitement, and primary negative symptoms. A mediational analysis revealed that changes in VM, inhibition, and EP partially explained the effect of cognitive remediation on functional competence improvement. This study provides initial evidence of the effect of integrative cognitive remediation on primary negative symptoms and creativity.

The impact of creativity on functional outcome in schizophrenia: a mediational model.

Functional impairment remains one of the most challenging issues for treatment in schizophrenia. However, previous studies have mainly focused on the negative impact of symptoms excluding variables that could positively impact functional outcome, such as creativity, which is considered an adaptive capacity for real-life problem-solving. This study analyzed the predictive role of creativity on functional outcome in 96 patients with schizophrenia through a mediational model, including sociodemographic, clinical, neurocognitive, and social cognitive variables. Path analysis revealed that creativity significantly mediated the relationship between neurocognition and functional outcome, and that creativity mediated between negative symptoms and functional outcome. Additionally, neurocognition was directly associated with functional outcome and social functioning was associated with creativity. The involvement of creativity in functional outcome could have relevant implications for the development of new interventions. These findings open up a new field of research on additional personal resources as possible factors of functional outcome in schizophrenia and other diseases.

Clinical, physical, physiological, and cardiovascular risk patterns of adults with schizophrenia: CORTEX-SP study: Characterization of adults with schizophrenia.

Schizophrenia (SP) is a severe mental illness with high rates of premature morbidity and mortality, associated with an unhealthy lifestyle and the side effects of drug treatment. The aims of the study were: 1) to determine some key physical, physiological and biochemical markers of health status, including sleep quality, in adults (42±10 yr) with SP (n=126), 2) to estimate cardiovascular risk (CVR), and 3) to compare all studied variables with a healthy control (HC) population (n=30). Assessment was based on body composition, blood pressure, cardiorespiratory condition, sleep quality with triaxial accelerometry for eight days and biochemical analysis. Participants with SP showed a cardiovascular risk profile including "overweight metabolically abnormal", low cardiorespiratory fitness, and impairment of ventilatory efficiency. Although individuals with SP slept more compared to HC, similar sleep efficiency was shown by both groups, but with significantly higher levels of wake after sleep onset by SP. The assessment of CVR revealed significantly higher values in SP (moderate risk) compared to HC (low risk) regardless of the estimation system. The identification of specific clinical, physical, and physiological CVR profiles in SP illness compared to healthy people strongly suggests targeting a comprehensive approach including non-pharmacological interventions. Clinical Trials.gov identifier, NCT03509597. Date of registration: April 26th, 2018.

Neurocognitive, social cognitive, and clinical predictors of creativity in schizophrenia.

BACKGROUND: Creativity is considered an essential human accomplishment and a key component for daily life problem solving. It has been suggested that impairment in working memory, cognitive flexibility, and theory of mind could lead to lower creativity in schizophrenia. Additionally, other neurocognitive and social cognitive domains, as well as clinical symptoms could play a role in this relationship. However, the extent to which each of these domains influences creativity in schizophrenia remains unknown. Therefore, the aim of this study was to simultaneously investigate the specific contribution of neurocognitive, social cognitive, and clinical variables to creativity in schizophrenia. METHODS: One hundred and one patients with schizophrenia were assessed in terms of sociodemographic, clinical, neurocognitive, social cognitive, and creativity variables. RESULTS: After controlling for sociodemographic variables, regression analyses showed that higher social perception (ß = 0.286, p = .004) and processing speed (ß = 0.219, p = .023) predicted creativity total score. Higher social perception (ß = 0.298, p = .002) and processing speed (ß = 0.277, p = .004) explained figural creativity. Finally, lower negative symptoms (ß = -0.302, p = .002) and higher social perception (ß = 0.210, p = .029) predicted verbal creativity. CONCLUSIONS: Results suggest that neurocognitive, social cognitive, as well as clinical symptoms influence creativity of patients with schizophrenia. Moreover, these findings point out the prominent role of social cognition in creativity in schizophrenia.

Brain White Matter Correlates of Creativity in Schizophrenia: A Diffusion Tensor Imaging Study.

The relationship between creativity and psychopathology has been a controversial research topic for decades. Specifically, it has been shown that people with schizophrenia have an impairment in creative performance. However, little is known about the brain correlates underlying this impairment. Therefore, the aim of this study was to analyze whole brain white matter (WM) correlates of several creativity dimensions in people with schizophrenia. Fifty-five patients with schizophrenia underwent diffusion-weighted imaging on a 3T magnetic resonance imaging machine as well as a clinical and a creativity assessment, including verbal and figural creativity measures. Tract-based spatial statistic, implemented in FMRIB Software Library (FSL), was used to assess whole brain WM correlates with different creativity dimensions, controlling for sex, age, premorbid IQ, and medication. Mean fractional anisotropy (FA) in frontal, temporal, subcortical, brain stem, and interhemispheric regions correlated positively with figural originality. The most significant clusters included the right corticospinal tract (cerebral peduncle part) and the right body of the corpus callosum. Verbal creativity did not show any significant correlation. As a whole, these findings suggest that widespread WM integrity is involved in creative performance of patients with schizophrenia. Many of these areas have also been related to creativity in healthy people. In addition, some of these regions have shown to be particularly impaired in schizophrenia, suggesting that these WM alterations could be underlying the worse creative performance found in this pathology.

Mediating role of cognition and social cognition on creativity among patients with schizophrenia and healthy controls: Revisiting the Shared Vulnerability Model.

AIM: As suggested by the Shared Vulnerability Model, impairment in executive functions could lead to worse creative performance among individuals with schizophrenia. Another impaired function in schizophrenia, previously related to creativity in healthy people, is theory of mind. However, little is known about the effect of theory of mind in creativity in schizophrenia. Therefore, the aim of this study was to analyze differences in creativity among patients with schizophrenia compared to healthy controls (HC) and to explore the potential role of executive functions and theory of mind as mediators of this relation. METHODS: Forty-five patients with schizophrenia and 45 HC underwent a neuropsychological assessment, including executive functions (cognitive flexibility and working memory), theory of mind, and verbal and figural creativity. RESULTS: As expected, patients with schizophrenia obtained lower scores in creativity, cognitive flexibility, working memory, and theory of mind compared to HC. Path analysis showed that theory of mind mediated the relation between group (schizophrenia or HC) and both figural (Z = 2.075, P = 0.037) and verbal creativity (Z = 2.570, P = 0.010). Working memory mediated the relation between group and figural creativity (Z = 2.034, P = 0.041) and was marginally significant for verbal creativity (Z = 1.930, P = 0.053). Finally, cognitive flexibility mediated between group and figural creativity (Z = 2.454, P = 0.014). CONCLUSION: Results suggest that the lower performance in creativity among patients with schizophrenia was partly due to an impairment in executive functions and theory of mind. The involvement of theory of mind opens up a new field of research as a possible risk factor in the Shared Vulnerability Model.