Predictors of adherence to exercise interventions in people with schizophrenia.

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants' characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia-Data From a Multicenter Randomized-Controlled Study.

BACKGROUND AND HYPOTHESIS: Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications. STUDY DESIGN: In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance. STUDY RESULTS: Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity. CONCLUSIONS: These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia. CLINICAL TRIALS REGISTRATION: The underlying study of this manuscript was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Exercise as an add-on treatment in individuals with schizophrenia: Results from a large multicenter randomized controlled trial.

Current treatment methods do not achieve recovery for most individuals with schizophrenia, and symptoms such as negative symptoms and cognitive deficits often persist. Aerobic endurance training has been suggested as a potential add-on treatment targeting both physical and mental health. We performed a large-scale multicenter, rater-blind, parallel-group randomized controlled clinical trial in individuals with stable schizophrenia. Participants underwent a professionally supervised six-month training comprising either aerobic endurance training (AET) or flexibility, strengthening, and balance training (FSBT, control group), follow-up was another six months. The primary endpoint was all-cause discontinuation (ACD); secondary endpoints included effects on psychopathology, cognition, functioning, and cardiovascular risk. In total, 180 participants were randomized. AET was not superior to FSBT in ACD and most secondary outcomes, with dropout rates of 59.55% and 57.14% in the six-month active phase, respectively. However, both groups showed significant improvements in positive, general, and total symptoms, levels of functioning and in cognitive performance. A higher training frequency additionally promoted further memory domains. Participants with higher baseline cognitive abilities were more likely to respond to the interventions. Our results support integrating exercise into schizophrenia treatment, while future studies should aim to develop personalized training recommendations to maximize exercise-induced benefits.

Fitness is positively associated with hippocampal formation subfield volumes in schizophrenia: a multiparametric magnetic resonance imaging study.

Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies.Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Associations between aerobic fitness, negative symptoms, cognitive deficits and brain structure in schizophrenia-a cross-sectional study.

Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.

Association between aerobic fitness and the functional connectome in patients with schizophrenia.

BACKGROUND: Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. OBJECTIVE: Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. METHODS: Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. RESULTS: Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. CONCLUSION: The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. TRIAL REGISTRATION: The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Aerobic endurance training to improve cognition and enhance recovery in schizophrenia: design and methodology of a multicenter randomized controlled trial.

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients' health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40-50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients' mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Personality Traits in Marathon Runners and Sedentary Controls With MMPI-2-RF.

BACKGROUND: Endurance exercise in general and marathon running in particular have become increasingly popular over the past decades. Recent investigations about personality structures in this cohort and comparisons to non-active cohorts are lacking. METHODS: In the ReCaP study (Running effects on Cognition and Plasticity), a total of 100 marathon runners and 46 sedentary controls were recruited. After elimination of Minnesota Multiphasic Personality Inventory 2 Restructured Form (MMPI-2-RF) profiles with insufficient validity, 79 marathon runners (MA) and 27 sedentary controls (SC) remained for final analyses. Depressive symptoms were evaluated with Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAMD). RESULTS: Marathon runners had lower scores in scales measuring somatic and cognitive complaints, stress, demoralization, hopelessness and distrust. Within the marathon group, committed runners exhibited hypomanic traits compared to regular runners. DISCUSSION AND CONCLUSION: Personality differences could be summarized as (sub-)depressive personality traits in SC compared to MA rather than typical (sub-) depressive symptoms in the meaning of depressive disorders. Future studies should further evaluate cause and consequence of endurance training and hypomanic or euthymic symptoms, as a two-way interaction exists. TRIAL REGISTRATION: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00012496.

Effects of Aerobic Exercise on Metabolic Syndrome, Cardiorespiratory Fitness, and Symptoms in Schizophrenia Include Decreased Mortality.

Schizophrenia is a severe psychiatric disorder with a lifetime prevalence of about 1%. People with schizophrenia have a 4-fold higher prevalence of metabolic syndrome than the general population, mainly because of antipsychotic treatment but perhaps also because of decreased physical activity. Metabolic syndrome is a risk factor for cardiovascular diseases, and the risk of these diseases is 2- to 3-fold higher in schizophrenia patients than in the general population. The suicide risk is also higher in schizophrenia, partly as a result of depression, positive, and cognitive symptoms of the disease. The higher suicide rate and higher rate of cardiac mortality, a consequence of the increased prevalance of cardiovascular diseases, contribute to the reduced life expectancy, which is up to 20 years lower than in the general population. Regular physical activity, especially in combination with psychosocial and dietary interventions, can improve parameters of the metabolic syndrome and cardiorespiratory fitness. Furthermore, aerobic exercise has been shown to improve cognitive deficits; total symptom severity, including positive and negative symptoms; depression; quality of life; and global functioning. High-intensity interval endurance training is a feasible and effective way to improve cardiorespiratory fitness and metabolic parameters and has been established as such in somatic disorders. It may have more beneficial effects on the metabolic state than more moderate and continuous endurance training methods, but to date it has not been investigated in schizophrenia patients in controlled, randomized trials. This review discusses physical training methods to improve cardiorespiratory fitness and reduce metabolic syndrome risk factors and symptoms in schizophrenia patients. The results of studies and future high-quality clinical trials are expected to lead to the development of an evidence-based physical training program for patients that includes practical recommendations, such as the optimal length and type of aerobic exercise programs and the ideal combination of exercise, psychoeducation, and individual weight management sessions.