Can structural MRI aid in clinical classification? A machine learning study in two independent samples of patients with schizophrenia, bipolar disorder and healthy subjects.

Although structural magnetic resonance imaging (MRI) has revealed partly non-overlapping brain abnormalities in schizophrenia and bipolar disorder, it is unknown whether structural MRI scans can be used to separate individuals with schizophrenia from those with bipolar disorder. An algorithm capable of discriminating between these two disorders could become a diagnostic aid for psychiatrists. Here, we scanned 66 schizophrenia patients, 66 patients with bipolar disorder and 66 healthy subjects on a 1.5T MRI scanner. Three support vector machines were trained to separate patients with schizophrenia from healthy subjects, patients with schizophrenia from those with bipolar disorder, and patients with bipolar disorder from healthy subjects, respectively, based on their gray matter density images. The predictive power of the models was tested using cross-validation and in an independent validation set of 46 schizophrenia patients, 47 patients with bipolar disorder and 43 healthy subjects scanned on a 3T MRI scanner. Schizophrenia patients could be separated from healthy subjects with an average accuracy of 90%. Additionally, schizophrenia patients and patients with bipolar disorder could be distinguished with an average accuracy of 88%.The model delineating bipolar patients from healthy subjects was less accurate, correctly classifying 67% of the healthy subjects and only 53% of the patients with bipolar disorder. In the latter group, lithium and antipsychotics use had no influence on the classification results. Application of the 1.5T models on the 3T validation set yielded average classification accuracies of 76% (healthy vs schizophrenia), 66% (bipolar vs schizophrenia) and 61% (healthy vs bipolar). In conclusion, the accurate separation of schizophrenia from bipolar patients on the basis of structural MRI scans, as demonstrated here, could be of added value in the differential diagnosis of these two disorders. The results also suggest that gray matter pathology in schizophrenia and bipolar disorder differs to such an extent that they can be reliably differentiated using machine learning paradigms.

The effects of physical exercise in schizophrenia and affective disorders.

Affective and non-affective psychoses are severe and frequent psychiatric disorders. Amongst others, they not only have a profound impact on affected individuals through their symptomatology, but also regarding cognition, brain structure and function. Cognitive impairment influences patients' quality of life as well as their ability to work and being employed. While exercise therapy has been implemented in the treatment of psychiatric conditions since the days of Kraepelin and Bleuler, the underlying mechanisms have never been systematically studied. Since the early 1990s, studies emerged examining the effect of physical exercise in animal models, revealing stimulation of neurogenesis, synaptogenesis and neurotransmission. Based on that body of work, clinical studies have been carried out in both healthy humans and in patient populations. These studies differ with regard to homogenous study samples, sample size, type and duration of exercise, outcome variables and measurement techniques. Based on their review, we draw conclusions regarding recommendations for future research strategies showing that modern therapeutic approaches should include physical exercise as part of a multimodal intervention programme to improve psychopathology and cognitive symptoms in schizophrenia and affective disorders.

Progressive muscle relaxation in persons with schizophrenia: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of this systematic review was to assess the effectiveness of progressive muscle relaxation on psychological distress and anxiety symptoms and on response/remission for people with schizophrenia. METHODS: Randomized controlled trials were considered if they investigated progressive muscle relaxation in patients with schizophrenia. EMBASE, PsycINFO, PubMed, ISI Web of Science, CINAHL, PEDro and Cochrane Library were searched. The selection of studies, data extraction and quality assessment were performed independently by two reviewers. RESULTS: Three randomized controlled trials involving 146 patients met the inclusion criteria. Progressive muscle relaxation can acutely reduce state anxiety and psychological distress and improve subjective well-being. No studies investigated the evidence for progressive muscle relaxation as an add-on treatment for general psychopathology and for positive or negative symptoms. Also, no studies assessed the value of progressive muscle relaxation in longer-term treatment and for relapse prevention. There were no data to draw any conclusions about progressive muscle relaxation in comparison with other treatment modalities. None of the studies encountered adverse events. Dose-response relationships could not be determined. CONCLUSION: Progressive muscle relaxation might be a useful add-on treatment to reduce state anxiety and psychological distress and improve subjective well-being in persons with schizophrenia.

Cardiorespiratory fitness and self-reported physical activity levels of referring mental healthcare professionals, and their attitudes and referral practices related to exercise and physical health.

BACKGROUND: Physical activity (PA) interventions can improve mental and physical health of people with mental illness, especially when delivered by qualified exercise professionals. Also, the behaviour, engagement and support of referring mental healthcare professionals (HCP) seem essential, but research is scarce. We aimed to study HCP physical fitness and PA, and associations with their attitudes and referral practices related to physical health and PA interventions. METHODS: HCP at the Dutch Association for Psychiatry congress (2019) were invited to an online questionnaire (demographic/work characteristics, stress, PA levels, knowledge/attitudes regarding PA, referral practices) and cycle ergometer test. Strongest associations were analysed using linear and logistic regression. RESULTS: Of the 115 HCP who completed the questionnaire (40 also completed the ergometer test), 43% (n = 50) met PA guidelines (i.e., ≥150min moderate-to-vigorous PA and ≥2x bone/muscle-strengthening exercises/week). Women, HCP interns/residents and HCP experiencing more stress were less active and less likely to meet PA guidelines. Conversely, there were positive associations with personal experience with an exercise professional. Knowledge/attitudes on physical health and PA were positive. HCP were more likely to refer patients to PA interventions if they met PA guidelines (OR = 2.56, 95%BI = 0.85-7.13) or had higher beliefs that exercise professionals can increase adherence to PA interventions (OR = 3.72, 95%BI = 1.52-9.14). LIMITATIONS: Mainly psychiatrists, affecting generalizability. CONCLUSIONS: HCP report the importance and relevance of PA in mental healthcare. Despite strong evidence and guidance for PA interventions in prevention and treatment, referral to such interventions partly depends on the PA behaviour and attitude of patient's physician/clinician.

Reduced resting state functional connectivity in the hippocampus-midbrain-striatum network of schizophrenia patients.

Contemporary preclinical models suggest that abnormal functioning of a brain network consisting of the hippocampus, midbrain and striatum plays a critical role in the pathophysiology of schizophrenia. Previous neuroimaging studies examined individual aspects of this model in schizophrenia patients and individuals at clinical high risk for psychosis. However, this exact preclinical brain network has not been translated to human neuroimaging studies with schizophrenia patients and therefore it is currently unknown how functioning of this network is altered in patients. Here we investigated resting state functional connectivity in the hippocampus-midbrain-striatum network of schizophrenia patients, using functional Magnetic Resonance Imaging. Based on preclinical models, a network of functionally validated brain regions comprising the anterior subiculum (SUB), limbic striatum (LS), ventral tegmental area (VTA) and associative striatum (AS) was examined in 47 schizophrenia patients and 51 healthy controls. Schizophrenia patients demonstrated significantly lower functional connectivity in this hippocampus-midbrain-striatum network compared with healthy controls (p = 0.036). Particular reductions in connectivity were found between the SUB and LS (0.002 ± 0.315 and 0.116 ± 0.224, p = 0.040) and between the VTA and AS (0.230 ± 0.268 and 0.356 ± 0.285, p = 0.026). In patients, functional connectivity was not significantly associated with positive, negative or general symptom scores. Reduced connectivity is consistent with the concept of functional brain dysconnectivity as a key feature of the disorder. Our results support the notion that functioning of the hippocampus-midbrain-striatum network is significantly altered in the pathophysiology of schizophrenia.

Low Physical Activity and Cardiorespiratory Fitness in People With Schizophrenia: A Comparison With Matched Healthy Controls and Associations With Mental and Physical Health.

Introduction: The aim of this study was to objectively assess time spent in physical activity (PA) and sedentary behavior (SB) in patients with schizophrenia compared to healthy controls matched for age, gender and socioeconomic status. Associations between both PA and cardiorespiratory fitness (CRF) and mental and physical health parameters in patients with schizophrenia were examined. Materials and Methods: Moderate and vigorous PA (MVPA), moderate PA, vigorous PA, total and active energy expenditure (TEE and AEE), number of steps, lying down and sleeping time was assessed with SenseWear Pro-2 body monitoring system for three 24-h bouts in patients with schizophrenia (n = 63) and matched healthy controls (n = 55). Severity of symptoms (Positive and Negative Syndrome Scale and Montgomery and Åsberg Depression Rating Scale), CRF (peak oxygen uptake, VO2peak), body mass index (BMI), and metabolic syndrome were assessed. Results: Patients with schizophrenia performed less MVPA and moderate activity had lower TEE and AEE, spent more time per day lying down and sleeping, and had poorer CRF compared to healthy controls. The amount of MVPA, but especially CRF was associated with severity of negative symptoms in patients with schizophrenia. Only CRF was associated with BMI. Discussion: The current data offer further evidence for interventions aiming to increase physical activity and decrease sedentary behavior. Given strong associations of CRF with both negative symptoms and BMI, treatment aimed at CRF-improvement may prove to be effective.

Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm.

The importance of self-determined motivation towards physical activity in patients with schizophrenia.

There is a need for theoretically-based research on the motivational processes linked to the commencement and continuation of physical activity in patients with schizophrenia. Within the Self-Determination Theory (SDT) framework, we investigated the SDT tenets in these patients by examining the factor structure of the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) and by investigating associations between motivation and PA. The secondary aim was to study differences in motivation according to gender, educational level, treatment setting and disease stage. A total of 129 patients (44♀) with schizophrenia agreed to participate. Exploratory factor analysis showed sufficient convergence with the original factor for amotivation, external and introjected regulation, while identified and intrinsic regulations loaded on a single factor which we labeled "autonomous regulation". Significant positive correlations were found between the total physical activity score and the subscales amotivation (r = -0.44, P < 0.001), external regulation (r = -0.27, P < 0.001), and autonomous regulation (r = 0.57, P < 0.001). Outpatients reported more external (P < 0.05) and introjected (P < 0.05) regulations than inpatients. Our results suggest that patients' level of self-determination may play an important role in the adoption and maintenance of health promoting behaviors in patients with schizophrenia.

Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls.

The objective of this study was to examine exercise effects on global brain volume, hippocampal volume, and cortical thickness in schizophrenia patients and healthy controls. Irrespective of diagnosis and intervention, associations between brain changes and cardiorespiratory fitness improvement were examined. Sixty-three schizophrenia patients and fifty-five healthy controls participated in this randomised controlled trial. Global brain volumes, hippocampal volume, and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test. Subjects were assigned exercise therapy or occupational therapy (patients) and exercise therapy or life-as-usual (healthy controls) for six months 2h weekly. Exercise therapy effects were analysed for subjects who were compliant at least 50% of sessions offered. Significantly smaller baseline cerebral (grey) matter, and larger third ventricle volumes, and thinner cortex in most areas of the brain were found in patients versus controls. Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls. Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal, temporal and cingulate cortex irrespective of diagnosis. One to 2h of exercise therapy did not elicit significant brain volume changes in patients or controls. However, cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls.

Effects of exercise therapy on cardiorespiratory fitness in patients with schizophrenia.

BACKGROUND: Increased mortality in schizophrenia is caused largely by coronary heart disease (CHD). Low cardiorespiratory fitness (CRF) is a key factor for CHD mortality. We compared CRF in patients with schizophrenia to CRF of matched healthy controls and reference values. Also, we examined the effects of exercise therapy on CRF in patients with schizophrenia and in controls. METHODS: Sixty-three patients with schizophrenia and 55 controls, matched for gender, age, and socioeconomic status, were randomized to exercise (n = 31) or occupational therapy (n = 32) and controls to exercise (n = 27) or life as usual (n = 28). CRF was assessed with an incremental cardiopulmonary exercise test and defined as the highest relative oxygen uptake (VO(2peak)) and peak work rate (W(peak)). Minimal compliance was 50% of sessions (n = 52). RESULTS: Male and female patients with schizophrenia had a relative VO(2peak) of 34.3 ± 9.9 and 24.0 ± 4.5 mL.kg(-1).min(-1), respectively. Patients had higher resting HR (P < 0.01) and lower peak HR (P < 0.001), peak systolic blood pressure (P = 0.02), relative VO(2peak) (P < 0.01), W(peak) (P < 0.001), RER (P < 0.001), minute ventilation (P = 0.02), and HR recovery (P < 0.001) than controls. Relative VO(2peak) was 90.5% ± 19.7% (P < 0.01) of predicted relative VO(2peak) in male and 95.9% ± 14.9% (P = 0.18) in female patients. In patients, exercise therapy increased relative VO(2peak) compared with decreased relative VO(2peak) after occupational therapy. In controls, relative VO(2peak) increased after exercise therapy and to a lesser extent after life as usual (group, P < 0.01; randomization, P = 0.03). Exercise therapy increased W(peak) in patients and controls compared with decreased W(peak) in nonexercising patients and controls (P < 0.001). CONCLUSION: Patients had lower CRF levels compared with controls and reference values. Exercise therapy increased VO(2peak) and W(peak) in patients and controls. VO(2peak) and W(peak) decreased in nonexercising patients.