High-intensity interval training and active video gaming improve neurocognition in schizophrenia: a randomized controlled trial.

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.

Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms.

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.

Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

Evaluation of the alcohol use disorders identification test and the drug use disorders identification test among patients at a Norwegian psychiatric emergency ward.

High rates of substance use disorders (SUD) among psychiatric patients are well documented. This study explores the usefulness of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) in identifying SUD in emergency psychiatric patients. Of 287 patients admitted consecutively, 256 participants (89%) were included, and 61-64% completed the questionnaires and the Mini-International Neuropsychiatric Interview (MINI), used as the reference standard. Both AUDIT and DUDIT were valid (area under the curve above 0.92) and reliable (Cronbach's alpha above 0.89) in psychotic and nonpsychotic men and women. The suitable cutoff scores for AUDIT were higher among the psychotic than nonpsychotic patients, with 12 versus 10 in men and 8 versus 5 in women. The suitable cutoff scores for DUDIT were 1 in both psychotic and nonpsychotic women, and 5 versus 1 in psychotic and nonpsychotic men, respectively. This study shows that AUDIT and DUDIT may provide precise information about emergency psychiatric patients' problematic alcohol and drug use.

The relationship between the brain-derived neurotrophic factor and neurocognitive response to physical exercise in individuals with schizophrenia.

OBJECTIVE: Physical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia. METHOD: The current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37 ± 14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models. RESULTS: Baseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF, but not baseline proBDNF, moderated the effect of exercise on neurocognition (p = 0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VO2max on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention (p = 0.036), regardless of exercise mode, differing by sex and associated with improved VO2max but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention. CONCLUSION: We found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.

Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia-a randomized controlled trial.

Background: In individuals with schizophrenia, inflammation is associated with depression, somatic comorbidity and reduced quality of life. Physical exercise is known to reduce inflammation in other populations, but we have only limited knowledge in the field of schizophrenia. We assessed inflammatory markers in plasma samples from individuals with schizophrenia participating in an exercise intervention randomized controlled trial. We hypothesized that (i) physical exercise would reduce levels of inflammatory markers and (ii) elevated inflammatory status at baseline would be associated with improvement in cardiorespiratory fitness (CRF) following intervention. Method: Eighty-two individuals with schizophrenia were randomized to a 12-week intervention of either high-intensity interval training (HIIT, n = 43) or active video gaming (AVG, n = 39). Participants were assessed at baseline, post intervention and four months later. The associations between exercise and the inflammatory markers soluble urokinase plasminogen activator receptor, c-reactive protein, tumor necrosis factor (TNF), soluble TNF receptor 1 and interleukin 6 (IL-6) were estimated using linear mixed effect models for repeated measures. For estimating associations between baseline inflammation and change in CRF, we used linear regression models. Results: Our main findings were (i) TNF and IL-6 increased during the intervention period for both groups. Other inflammatory markers did not change during the exercise intervention period; (ii) baseline inflammatory status did not influence change in CRF during intervention, except for a positive association between baseline IL-6 levels and improvements of CRF to post intervention for both groups. Conclusion: In our study, HIIT and AVG for 12-weeks had no reducing effect on inflammatory markers. Patients with high baseline IL-6 levels had a positive change in CRF during intervention. In order to increase our knowledge regarding association between inflammatory markers and exercise in individuals with schizophrenia, larger studies with more frequent and longer exercise bout duration are warranted.

High-intensity interval training may reduce depressive symptoms in individuals with schizophrenia, putatively through improved VO2max: A randomized controlled trial.

Introduction: High-intensity interval training (HIIT) may improve cardiorespiratory fitness (CRF) and mental health. The current observer-blinded RCT investigates the sparsely studied efficiency of HIIT in reducing psychotic and non-psychotic symptoms in schizophrenia and complements previous studies by investigating whether symptom reduction following HIIT is associated with, putatively partly mediated by, increased VO2max. Methods: Participants (outpatients meeting diagnostic criteria for schizophrenia) were randomized to HIIT (n = 43) or a comparison group performing low-intensity active video gaming (AVG) to control for social interaction (n = 39). Both interventions consisted of two supervised sessions/week for 12 weeks and a 4 months follow-up. Effects on overall symptoms and symptom domains [PANSS (0-6 scale), five-factor model] were estimated using mixed-effects models (intention-to-treat, n = 82). Underlying mechanisms were analyzed using moderated mediation analyses (n = 66). We anticipated that HIIT would reduce overall symptoms, particularly depressive symptoms, more than AVG, and symptom reduction would be associated with, putatively mediated through, improved VO2max. Results: Depressive symptoms (baseline score 3.97, 95% CI: 3.41, 4.52), were -1.03 points more reduced in HIIT than AVG at post-intervention (95% CI: -1.71, -0.35, p = 0.003), corresponding to a small to moderate effect size (d = 0.37) and persisting at follow-up. There was a small reduction in overall symptoms, but no significant between-group differences were observed. Change in VO2max correlated negatively with the change in depressive symptoms. Mediation analysis showed a significant effect of change in VO2max on change in depressive symptoms within HIIT. The total effect was moderated by group, and depressive symptoms were more reduced in HIIT. Direct effects, not mediated through VO2max, were non-significant. Indirect effects, mediated through VO2max, were non-significant, but the moderated mediation test indicated a non-significant trend of 0.4 points (95% CI: -1.188, 0.087) and a larger reduction in depressive symptoms through VO2max in HIIT. Conclusion: HIIT reduced depressive symptoms more than AVG, which persisted at follow-up. HIIT may serve as a complementing treatment option targeting these symptoms in individuals with schizophrenia, even before they reach clinical depression. Depressive symptoms are important to prevent, stabilize, and treat due to their negative implications for psychological wellbeing and long-term functional outcome. Reduction in depressive symptoms was associated with improved VO2max, and non-significant trends in the data supported that improved VO2max may be part of the complex mechanisms underlying the anti-depressive effect of HIIT. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02205684].

Psychoactive substance use among patients admitted to an acute psychiatric ward: laboratory findings and associations with clinical characteristics.

BACKGROUND: Estimates of psychoactive substance use among acutely admitted psychiatric patients vary among studies, and few have used comprehensive laboratory methods. AIMS: This study used chromatography-based analyses of blood and urine to identify the rates of substance use among acute psychiatric admissions, and to study the associations with socio-demographic variables, clinical characteristics and patients' reports of symptoms, substance use and need for treatment. METHODS: A cross-sectional study was conducted in 2006/2007 in Oslo, Norway. Blood and urine samples were collected from 298 acute psychiatric admissions and extensively analysed for alcohol, medicinal and illicit drugs. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Patient self-report questionnaires included the Alcohol and Drug Use Disorder Identification Tests. Patients were also asked if they needed professional help for substance use. RESULTS: Psychoactive substances were detected in 63% of the 298 admissions, medicinal drugs in 46%, alcohol in 12% and illicit drugs in 28%. Patients using alcohol had a high suicidal risk score at admission and the shortest length of stay (median 1 day). Use of illicit drugs was associated with psychotic symptoms and readmission. Self-report questionnaires indicated harmful use of alcohol for half of the patients and of other substances for one-third. A need for professional help for substance use was reported by one-third of patients. CONCLUSION: Given the high rates of substance use and the important clinical associations, drug screening seems warranted in acute psychiatric settings. Interventions designed for substance-using patients should be developed and integrated.

Recent substance intake among patients admitted to acute psychiatric wards: physician's assessment and on-site urine testing compared with comprehensive laboratory analyses.

This cross-sectional study of acute psychiatric admissions compared physicians' assessments of recent substance intake and on-site urine testing with comprehensive laboratory drug analyses. The sample comprised 325 consecutive admissions from 2 acute psychiatric wards. Physicians on call were asked to judge if the patient had recently taken benzodiazepines, opiates, alcohol, amphetamines, cannabis, or cocaine. Blood and urine samples were obtained and analyzed with chromatographic laboratory methods for a wide range of substances. A routine on-site urine screening test was performed in 92 of the cases. Physicians' assessments and on-site urine testing were compared with the reference standard of laboratory analyses. The sensitivity of the physician's assessment was highest for amphetamines (76%), followed by benzodiazepines (61%), opiates (57%), cannabis (55%), and cocaine (50%), whereas specificity was greater than 90% for all substances. The sensitivity of the on-site test ranged from 76% for amphetamine to 97% for cannabis, and specificity ranged from 82% for cannabis to 100% for cocaine. The study indicates clinical underdetection of recent substance intake among acute psychiatric admissions. On-site urine testing identified substance use that was not recognized by the physician's initial assessment, although specificity for cannabis and benzodiazepines was low. Chromatographic methods, which offered important supplementary information about substance use, should be considered for the routine screening of acutely admitted psychiatric patients.

The Association Between Cardiorespiratory Fitness and Cognition Appears Neither Related to Current Physical Activity Nor Mediated by Brain-Derived Neurotrophic Factor in a Sample of Outpatients With Schizophrenia.

Objective: We investigated whether levels of current physical activity (PA) contribute to the established relationship between cardiorespiratory fitness (CRF) and cognition in schizophrenia and whether brain-derived neurotrophic factor (BDNF) or its precursor proBDNF mediates this relationship. Method: Sixty-one outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale (WAIS) and nine subtests from the MATRICS battery comprising a neurocognitive composite score (NCS). CRF was assessed with peak oxygen uptake (VO2peak) measured directly during a maximum exercise test. Current PA levels were objectively assessed by an accelerometer worn for four consecutive days. BDNF and proBDNF were measured in fasting blood. Four serial parallel mediation analyses and two additional parallel mediation analyses were conducted, while controlling for age and sex at all levels. Results: No direct effects were found between PA measures and WAIS or NCS. No significant mediating effects of CRF or BDNF/proBDNF were detected. Conclusion: The results do not support the hypothesis that PA contributes to the naturally occurring relationship between CRF and cognition in schizophrenia or the hypothesis that BDNF or proBDNF mediates this relationship. The results arguably support the assumption that the association between CRF and cognition in schizophrenia is established developmentally early. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02205684.

Objectively Assessed Daily Steps-Not Light Intensity Physical Activity, Moderate-to-Vigorous Physical Activity and Sedentary Time-Is Associated With Cardiorespiratory Fitness in Patients With Schizophrenia.

People with schizophrenia often have an unhealthy sedentary lifestyle with low level of physical activity and poor cardiorespiratory fitness-an important predictor of cardiovascular disease. We investigated the relations between cardiorespiratory fitness and both sedentary time and different aspects of physical activity, such as daily steps, light intensity physical activity, and moderate-to-vigorous physical activity. Using accelerometer as an objective measure of sedentary time and physical activity we estimated their relations to cardiorespiratory fitness in 62 patients with schizophrenia with roughly equal gender distribution, mean age of 36 and 15 years illness duration. We found a significant association between daily steps and cardiorespiratory fitness when accounting for gender, age, sedentary time, light intensity physical activity, and respiratory exchange ratio (maximal effort). Moderate-to-vigorous physical activity was not significantly associated with cardiorespiratory fitness. In conclusion, the amount of steps throughout the day contributes to cardiorespiratory fitness in people with schizophrenia, independently of light intensity physical activity and sedentary time. We did not find a significant relationship between moderate-to-vigorous physical activity and cardiorespiratory fitness. This may have implications for the choice of strategies when helping patients with schizophrenia improve their cardiorespiratory fitness.

Drugs of abuse among acute psychiatric and medical admissions: laboratory based identification of prevalence and drug influence.

OBJECTIVE: To use laboratory based analyses of blood and urine to determine the prevalence and influence of drugs of abuse among acute psychiatric and medical admissions. METHOD: In a cross sectional study, urine and blood samples were collected from 100 psychiatric and 106 medical admissions and extensively analysed for legal drugs with abuse potential, alcohol and illegal drugs. Drug influence at the time of admission was estimated on the basis of blood drug concentrations. RESULTS: Legal drugs were found in 47% of the psychiatric and 42% of the medical admissions. Alcohol was detected in 8% of the psychiatric and 4% of medical admissions, and illegal drugs were detected in 36% of the psychiatric and 13% of the medical admissions. Drug influence was estimated in 26% of the psychiatric and 14% of the medical patients. CONCLUSION: This study shows widespread use of substances among psychiatric and medical inpatients and that many are under the influence of drugs on admission.

Effects of high-intensity aerobic exercise on psychotic symptoms and neurocognition in outpatients with schizophrenia: study protocol for a randomized controlled trial.

BACKGROUND: The focus in recent years on physical inactivity and metabolic disturbances in individuals with schizophrenia raises the question of potential effects of physical activity. Physical activity has shown beneficial effects on cognition in healthy older individuals as well as on symptom severity in depression. However, opinions diverge regarding whether aerobic high-intensity interval training reduces cognition and key symptoms in schizophrenia. The main objective for the trial is to investigate the potential effects of aerobic high-intensity interval training on neurocognitive function and mental symptoms in outpatients with schizophrenia. METHODS/DESIGN: The trial is designed as a randomized controlled, observer-blinded clinical trial. Patients are randomized to 1 of 2 treatment arms with 12-week duration: aerobic high-intensity interval training or computer gaming skills training. All participants also receive treatment as usual. Primary outcome measure is neurocognitive function. Secondary outcome measures will be positive and negative symptoms, wellbeing, tobacco-smoking patterns and physiological/metabolic parameters. Patient recruitment takes place in catchment area-based outpatient clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT02205684 . Registered 29 July 2014.

A comparison of symptoms and drug use between patients with methamphetamine associated psychoses and patients diagnosed with schizophrenia in two acute psychiatric wards.

Psychosis induced by the use of amphetamine or methamphetamine leads to dramatic symptoms and frequent readmissions and poses diagnostic challenges. Earlier studies have often relied on history taking and/or urine samples to reveal drug use. The aim of this study was to compare the psychotic symptoms of two groups: (1) acutely admitted patients who tested positive for methamphetamines and were diagnosed with drug-induced or methamphetamine-induced psychoses and (2) acutely admitted patients who tested negative for methamphetamines and were diagnosed with schizophrenia. Blood and urine samples were used. In addition, we investigated whether the severity of symptoms, in those who tested positive, was related to the blood concentration of methamphetamine. Of 285 patients who volunteered blood and/or urine samples within 48h of admission, 37 (13%) had recently taken methamphetamine. Positive psychotic symptoms between the two groups were compared by PANSS using the positive subscale. The results showed no differences in positive psychotic symptoms between the two groups. The severity of positive psychotic symptoms in patients with three different levels of urine/blood methamphetamine concentrations, were compared. We found no clinically or statistically significant relationship between blood methamphetamine levels and severity of psychotic symptoms.

Comparison of drug concentrations in blood and oral fluid collected with the Intercept sampling device.

The aim of the study was to determine drug concentration ratios between oral fluid collected with the Intercept device and whole blood. Samples of blood and oral fluid were obtained from patients admitted to acute psychiatric treatment and drivers suspected of drugged driving. Samples were analyzed for illegal drugs, benzodiazepines, opioids, carisoprodol, and meprobamate. Drugs were detected in samples of both blood and oral fluid from 59 subjects; altogether, 17 different drugs were found. Concentration ratios between oral fluid and blood were determined for all cases. The distributions of drug concentration ratios were wide for most drugs and do not allow reliable estimations of drug concentrations in blood using concentrations in oral fluid. The median oral fluid/blood drug concentration ratios for the most prevalent drugs were 0.036 diazepam, 0.027 nordiazepam, 7.1 amphetamine, 2.9 methamphetamine, 5.4 codeine, 1.9 morphine, and 4.7 tetrahydrocannabinol. The correlation coefficients between drug concentrations in oral fluid and blood ranged from 0.15 to 0.96 for the six most prevalent drugs.