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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.
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Physical activity (PA) has positive effects on various health aspects and neuronal functions, including neuronal plasticity. Exceeding a certain exercise frequency and duration has been associated with negative effects. Our study investigated the effects of excessive PA with a marathon run (MA) and regular PA (training and recovery phases) on electrocortical activity, as measured by electroencephalography (EEG). Thirty healthy marathon runners (26 male, 45 ± 9 yrs) were enrolled in the study. Four resting-state 32 channel EEG recordings were conducted: 12-8 weeks before MA (T-1), 14-4 days prior to MA (T0), 1-6 days after (T2), and 13-15 weeks after MA (T3). Power spectrum analyses were conducted using standardized Low-Resolution Electromagnetic Tomography (sLORETA) and included the following frequency bands: delta (1.5-6 Hz), theta (6.5-8.0 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-12.0 Hz), beta1 (12.5-18.0 Hz), beta2 (18.5-21.0 Hz), beta3 (21.5-30.0 Hz), and total power (1.5-30 Hz). Statistical nonparametric mapping showed reduced power both in the alpha-2 (log-F ratio = - 0.705, threshold log-F ratio = ± 0.685, p < 0.05) and in the delta frequency band (log-F ratio = -0.699, threshold log-F ratio = ± 0.685, p < 0.05) in frontal cortical areas after MA (T2 vs. T0). These effects diminished at long-term follow-up (T3). The results can be interpreted as correlates for subacute neuroplasticity induced by strenuous and prolonged PA. Although previous studies reported an increase in alpha frequency during and directly postexercise, the adverse observation a few days after exercise cessation suggests counterregulatory mechanisms, whose complex origin can be suspected in subcortical circuits, changes in neurotransmitter systems and modulation of affectivity.
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Eletroencefalografia , Corrida de Maratona , Humanos , Masculino , Encéfalo , Eletroencefalografia/métodos , Lobo Frontal , Estudos Longitudinais , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
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).
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Conectoma , Esquizofrenia , Teorema de Bayes , Encéfalo/diagnóstico por imagem , Estudos Transversais , Exercício Físico , Humanos , Imageamento por Ressonância Magnética , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagemRESUMO
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).
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Treino Aeróbico , Reabilitação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Esquizofrenia/reabilitação , Adolescente , Adulto , Idoso , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Aerobic endurance training has been discussed to induce brain plasticity and improve cognitive functions in healthy subjects and patients with neuropsychiatric disorders. For schizophrenia, a motor cortical inhibitory deficit has been established as one aspect of impaired plasticity, especially involving impairments in GABAergic interneuron networks, but the possibility to restore these deficits via exercise-induced plasticity has not been evaluated yet. METHODS: 17 schizophrenia patients and 16 matched healthy controls underwent 3 months of aerobic endurance training (30 min, 3 times a week) on bicycle ergometers. After 6 weeks, computer-assisted cognitive remediation training (30 min, 2 times a week) was added. Transcranial magnetic stimulation of the left and right hemispheres was performed at baseline and at the end of the intervention. We evaluated the intensity to induce a motor-evoked potential of 1 mV (S1mV), the resting motor threshold (RMT), the cortical silent period (CSP) at an intensity of 120 and 150% of the individual RMT, short-latency interval intracortical inhibition (3 ms), and intracortical facilitation (7 and 15 ms). Depending on the variable and hemisphere, follow-up data was available for 7-15 schizophrenia patients and for 10-12 healthy controls. RESULTS: Repeated measures ANOVA revealed no significant time × group interactions for any of the analyzed variables. A significant increase in S1mV and CSP duration at 150% RMT of the left hemisphere could be observed in both groups over time. CONCLUSION: Regular ergometer training over 3 months increases motor cortical inhibition as displayed by an increase in CSP. The increase in S1mV may also indicate a higher degree of inhibition after the intervention. We could not establish a difference between schizophrenia patients and healthy controls. Due to the limited sample size, our results have to be considered as preliminary and need to be replicated in future trials.
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Introduction: To date, concrete recommendations for physical activity in psychiatric treatments are limited. Thus, we evaluated knowledge, barriers and beliefs associated with exercise prescription of mental health professionals (MHP) to people with mental illnesses. We aimed to identify patients' barriers to exercise participation and to work out options addressing these barriers. Methods: In our cross-sectional and questionnaire-based investigation, we recruited medical, nursing and therapeutic staff and patients of a psychiatric clinic by email and personal contact. Questionnaires contained the German versions of The Exercise in Mental Illness Questionnaire (EMIQ-G) and the International Physical Activity Questionnaires (IPAQ). Results: We included 100 MHP and 100 patients. MHP had significantly more knowledge regarding positive effects of exercise on general health than patients. Exercise was prescribed mostly (48.4%) or always (37.9%) by MHP. The data showed missing education in exercise prescriptions and different recommendation behavior. Male patients seemed to experience exercise more often as a positive distraction and had lower physical health barriers than females. Discussion: Physical activity needs to be more integrated in psychiatric treatments. Some strategies as educating MHP and patients regarding potential benefits of exercise via psychoeducative brochures and adapting recommendations to individual symptoms could improve exercise behavior in psychiatric patients.
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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).
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Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/terapia , Teorema de Bayes , Exercício Físico/fisiologia , Encéfalo/diagnóstico por imagem , Terapia por Exercício/métodosRESUMO
Background: Prolonged and strenuous exercise has been linked to potential exercise-induced myocardial damages. One potential key to unmask the discussed underlying mechanisms of this subclinical cardiac damage could be markers of immunogenic cell damage (ICD). We investigated the kinetics of high-mobility group box 1 protein (HMGB1), soluble receptor for advanced glycation end products (sRAGE), nucleosomes, high sensitive troponin T (hs-TnT) and high sensitive C-reactive protein (hs-CRP) before and up to 12 weeks post-race and described associations with routine laboratory markers and physiological covariates. Methods: In our prospective longitudinal study, 51 adults (82% males; 43 ± 9 years) were included. All participants underwent a cardiopulmonary evaluation 10-12 weeks pre-race. HMGB1, sRAGE, nucleosomes, hs-TnT and, hs-CRP were analysed 10-12 weeks prior, 1-2 weeks before, immediately, 24 h, 72 h, and 12 weeks post-race. Results: HMGB1, sRAGE, nucleosomes and hs-TnT increased significantly from pre- to immediately post-race (0.82-2.79 ng/mL; 1132-1388 pg/mL; 9.24-56.65 ng/mL; 6-27 ng/L; p < 0.001) and returned to baseline within 24-72 h. Hs-CRP increased significantly 24 h post-race (0.88-11.5 mg/L; p < 0.001). Change in sRAGE was positively associated with change in hs-TnT (rs = 0.352, p = 0.011). Longer marathon finishing time was significantly associated with decreased levels of sRAGE [-9.2 pg/mL (ß = -9.2, SE = 2.2, p < 0.001)]. Conclusion: Prolonged and strenuous exercise increases markers of ICD immediately post-race, followed by a decrease within 72 h. An acute marathon event results in transient alterations of ICD, we assume that this is not solely driven by myocyte damages.
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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.
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Transtornos Cognitivos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/terapia , Exercício Físico , Terapia por Exercício/métodos , Transtornos Cognitivos/complicações , CogniçãoRESUMO
Introduction: The impact of psychiatric medications and their enhancing or impairing effects on physical performance remains inconclusive. Therefore, with this systematic review we provide a comprehensive overview of frequently used psychotropic drugs and their effects on physical performance for the purpose of providing empirical information and deriving prescription and therapy recommendations for clinical practice. Methods: We systematically searched PubMed, PsycInfo, and Cochrane databases and extracted human studies investigating the effect of psychotropic drugs on parameters associated with the level of physical performance, such as exercise time, oxygen consumption, heart rate, muscle contraction or blood lactate concentration in physically healthy participants. 36 studies - comprising a broad range of psychotropic agents, such as antidepressants, antipsychotics, sedatives, and stimulants - were selected for final analyses. Results: Most studies (N = 32) were randomized controlled trials (RCT) with a double-blind crossover design. Antidepressants (N = 21) were the most frequently studied drug class, with contradictory results e.g., performance enhancement in warm environment but not in temperate conditions for bupropion or inconsistent findings between studies for other antidepressants. Antipsychotics (N = 3) mainly showed impairing effects on physical performance, while stimulants (N = 4) were often performance-enhancing. Sedatives (N = 9) may cause a hangover effect. Conclusion: The examined studies with heterogeneous design showed different effects of psychiatric medications on physical performance. Antipsychotics seemed to be performance impairing, while the findings for antidepressants and sedatives were more inconsistent. Stimulants were the only group with consistent performance-enhancing effects. However, most studies were conducted with a small sample size (N < 10), mostly in well-trained subjects rather than in patients with psychiatric disorders, and most studies used single-dose designs. These issues impede the formulation of generalized conclusions for treatment regimes and should therefore be considered in further longitudinal studies for clinically reliable statements. Nevertheless, answering our research question is quite relevant for clinical practice and therapeutic prescription and should be further investigated especially considering the high drop-out rates in drug treatment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=276103], identifier [CRD42021276103].
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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).
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Imageamento por Ressonância Magnética Multiparamétrica , Esquizofrenia , Adulto , Estudos Transversais , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Tamanho do Órgão , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologiaRESUMO
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.
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Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far. Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses. Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F (4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort. Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.
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INTRODUCTION: Physical activity has beneficial effects on both cardiovascular and neurocognitive parameters, and these two modalities are known to interact at rest. However, findings on their interaction during exercise are inconclusive. PURPOSE: Therefore, this longitudinal study aimed to investigate the effects of different forms of exercise (training period, marathon race, and recovery period) on both parameters and their interaction. METHODS: We included 100 marathon runners (MA) (mean ± SD age = 43.6 ± 10.0 yr, 80 males) and 46 age- and sex-matched sedentary controls (SC, for baseline comparison). Over the 6-month study period with six visits (12 and 2 wk before the marathon; immediately, 24 h, 72 h, and 12 wk after the marathon), we assessed cognitive parameters by evaluating the 1- to 3-back d prime, the d2 task, and the Trail Making Tests A (TMT A) and B (TMT B), and the retinal vessel parameters by assessing arteriolar-to-venular ratio (AVR), central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE). RESULTS: In the long-term analysis, 3-back d prime correlated positively with AVR (P = 0.024, B = 1.86, SE = 0.824) and negatively with CRVE (P = 0.05, B = -0.006, SE = 0.003), and TMT B correlated negatively with CRAE (P = 0.025, B = -0.155, SE = 0.069), even after correcting for age and systolic blood pressure as possible confounders. Acute effects were inconsistent with maximal cognitive improvement 24 h after the marathon. AVR was significantly smaller in SC compared with MA. CONCLUSION: Chronic exercise seems to prime the central nervous system for acute, intensive bouts of exercise. Our findings indicate a possible relationship between cognitive performance in high-demand tasks and retinal vasculature and support the idea of a neuroplastic effect of exercise.
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Cognição/fisiologia , Corrida de Maratona/fisiologia , Corrida de Maratona/psicologia , Vasos Retinianos/fisiologia , Adulto , Arteríolas/fisiologia , Pressão Sanguínea/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vênulas/fisiologiaRESUMO
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.
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BACKGROUND: Preclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments. AIMS: To evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia. METHODS: The add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures. CONCLUSIONS: SPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment. CLINICAL TRIAL REGISTRATION: International Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE.
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Strenuous exercise results in transient but minor alterations in left ventricular diastolic function (LVDF). The aim of this study is to describe and interpret the kinetics of the well-established 2D parameters of diastolic function and the novel and very sensitive 3D parameters before/after a marathon race. LVDF was evaluated by transthoracic echocardiography (TEE) in 212 healthy male [aged 42 (36-49) years)] marathon runners (all Be-MaGIC-study) in the week prior to (V1), immediately after (V2), 24 h after (V3) and 72 h after (V4) a marathon race. Real time three-dimensional echocardiography (RT3DE) included maximal and minimal left atrium (LA) volume, total LA ejection fraction (Total-EF), total LA stroke volume (Total-SV), true ejection fraction (True-EF) and atrial stroke volume (ASV). After adjustment for possible confounders (heart rate and systolic blood pressure), 2D Parameters of left ventricular inflow (E/A-ratio) decreased from pre- to immediately post-race (- 0.3 ± 0.06, p < 0.001) and returned to baseline within 24 h. [Formula: see text]-ratio remained unchanged directly post-race, but was significantly increased during follow-up of 24 and 72 h. 3D LA Vmin was increased immediately postrace and in the 24 h follow-up, LA Vmax was increased immediately post-race and in the follow-up of 24 and 72 h. During follow-up of 72 h, but not immediately postrace, TrueEF and ASV were significantly increased. Both techniques revealed acute and prolonged alterations of diastolic LV function. Considering all parameters, the recovery of diastolic LV after a marathon seems to take longer than previously assumed.Trial registration ClinicalTrials.gov ID: NCT00933218.
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Ecocardiografia Doppler de Pulso , Ecocardiografia Tridimensional , Ventrículos do Coração/diagnóstico por imagem , Resistência Física , Corrida , Função Ventricular Esquerda , Adulto , Fenômenos Biomecânicos , Ensaios Clínicos como Assunto , Diástole , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Background: The beneficial effects of exercise training on depressive symptoms are well-established. In the past years, more research attention has been drawn to the specific effects of exercise training on depressive symptoms in somatically ill patients. This reviews aims at providing a comprehensive overview of the current findings and evidence of exercise interventions in somatic disorders to improve depressive symptoms. Methods: We systematically searched PubMed and Cochrane databases and extracted meta-analyses from somatically ill patients that underwent exercise interventions and provided information about the outcome of depressive symptoms. Results: Of the 4123 detected publications, 39 were selected for final analysis. Various diseases were included (breast-cancer, prostate cancer, mixed-cancer, cardiovascular disease, coronary heart disease, hemodialysis, fibromyalgia syndrome, acute leukemia, other hematological malignancies, heart failure, HIV, multiple sclerosis, mixed neurological disorders, Parkinson's disease, stroke, ankylosing spondylitis, traumatic brain injury, lupus erythematodes). Most meta-analyses (33/39) found beneficial effects on depressive symptoms, but quality of the included studies as well as duration, intensity, frequency, and type of exercise varied widely. Conclusion: Exercise training has the potential to improve depressive symptoms in patients with somatic disorders. For specific training recommendations, more high quality studies with structured exercise programs and better comparability are needed.
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The main objective of this review was to evaluate studies on the diagnosis, treatment, and course of schizotypal personality disorder and to provide a clinical guidance on the basis of that evaluation. A systematic search in the PubMed/MEDLINE databases was conducted. Two independent reviewers extracted and assessed the quality of the data. A total of 54 studies were eligible for inclusion: 18 were on diagnostic instruments; 22, on pharmacological treatment; 3, on psychotherapy; and 13, on the longitudinal course of the disease. We identified several suitable and reliable questionnaires for screening (PDQ-4+ and SPQ) and diagnosing (SIDP, SIDP-R, and SCID-II) schizotypal personality disorder. Second-generation antipsychotics (mainly risperidone) were the most often studied drug class and were described as beneficial. Studies on the longitudinal course described a moderate remission rate and possible conversion rates to other schizophrenia spectrum disorders. Because of the heterogeneity of the studies and the small sample sizes, it is not yet possible to make evidence-based recommendations for treatment. This is a systematic evaluation of diagnostic instruments and treatment studies in schizotypal personality disorder. We conclude that there is currently only limited evidence on which to base treatment decisions in this disorder. Larger interventional trials are needed to provide the data for evidence-based recommendations.