Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022.

PURPOSE: To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE). METHODS: This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified. RESULTS: Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease. CONCLUSION: This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease. TRIAL REGISTRATION: Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.

Effects of auditory white noise stimulation on sustained attention and response time variability.

Introduction: "The moderate brain arousal model" claims that white noise improves attention by optimizing brain arousal. We analyze Conners' Continuous Performance Test-3 (CCPT-3) performance, expecting to find reduced reaction time variability with noise mediated by decrease under long event-rates and in later parts of the test, indicating that noise reverse fall in phasic and tonic arousal. Methods: Sixty-five children with high or lower ADHD-symptoms from a child psychiatric unit, succeeded to complete the CCPT-3 with and without white noise. Results: Noise reduced overall variability, improved performance in later parts of the test, and reduced response variability under the longest event rate particularly in the high symptoms group. No overall change in omissions and commissions, but the high symptoms group made fewer omissions during noise compared the low symptom group. Discussion: The study indicates an arousal effect of noise but should be replicated with other noise variants and amplitudes to improve effect and compliance.

Patterns of proactive interference in CVLT-II: evidence of a low-organized, disorganized, and highly organized learning style.

OBJECTIVE: Previous studies have interpreted proactive interference (PI) either as indicating executive dysfunction or a normal process indicating deep level encoding. We investigated these competing models of PI in a large clinical sample using cluster analyses. We expected to find clusters defined by high PI but otherwise characterized by either EF impairment or of good memory performance. METHOD: File records of 731 patients with neurological or psychiatric disorders were analyzed. PI-scores, false positive recognition errors, and semantic organization scores on the California Verbal Learning Test-II (CVLT-II) were subjected to cluster analyses. Clusters were compared regarding buildup and release from PI, memory performance and strategy measures, measures of intelligence, EF, and processing speed. RESULTS: The analyses revealed six analyzable clusters. Two clusters showed no buildup of PI and normal release from PI. Discriminability was impaired both in List A and B. Learning acquisition and speeded measures of EF were reduced. One cluster showed both buildup of PI and problems with releasing from PI, and particularly impaired discriminability of List B. Semantic organization was low. Learning consolidation and EF speeded measures were impaired. Two other clusters showed buildup of PI, but no problem with release. Learning was highly organized, and they showed good memory and normal neuropsychological performance. CONCLUSIONS: Results shows differentiation between a low organized EF dysfunction pattern with no PI, a disorganized PI pattern also indicating EF dysfunction and a highly organized pattern where PI seems to be the price to pay for high effort put into the learning process.

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.

Improving validity of the trail making test with alphabet support.

Objective: The Trail Making Test (TMT) is commonly used worldwide to evaluate cognitive decline and car driving ability. However, it has received critique for its dependence on the Latin alphabet and thus, the risk of misclassifying some participants. Alphabet support potentially increases test validity by avoiding misclassification of executive dysfunction in participants with dyslexia and those with insufficient automatization of the Latin alphabet. However, Alphabet support might render the test less sensitive to set-shifting, thus compromising the validity of the test. This study compares two versions of the TMT: with and without alphabet support. Methods: We compared the TMT-A, TMT-B, and TMT-B:A ratios in two independent normative samples with (n = 220) and without (n = 64) alphabet support using multiple regression analysis adjusted for age and education. The sample comprised Scandinavians aged 70-84 years. Alphabet support was included by adding the Latin alphabet A-L on top of the page on the TMT-B. We hypothesized that alphabet support would not change the TMT-B:A ratio. Results: After adjusting for age and years of education, there were no significant differences between the two samples in the TMT-A, TMT-B, or the ratio score (TMT-B:A). Conclusion: Our results suggest that the inclusion of alphabet support does not alter TMT's ability to measure set-shifting in a sample of older Scandinavian adults.

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.

Neuropsychological and Symptom Predictors of Diagnostic Persistence in ADHD: A 25-Year Follow-up Study.

BACKGROUND: This study extends long-term predictive research on ADHD by including both neuropsychological and symptom measures at baseline in adolescence as predictors of diagnostic persistence 25 years later. METHODS: Nineteen males with ADHD and 26 healthy controls (HC; M/F = 13/13), were assessed in adolescence and 25 years later. Measurements at baseline included a comprehensive test battery measuring eight neuropsychological domains, an IQ estimate, the Child Behavior Checklist (CBCL), and the Global Assessment Scale of Symptoms. Differences between ADHD Retainers, Remitters, and HC were calculated with ANOVAs, and potential predictions of differences in the ADHD group by linear regression analyses. RESULTS: Eleven (58%) participants retained their ADHD diagnoses at follow-up. Motor Coordination and Visual perception at baseline predicted diagnosis at follow-up. CBCL Attention problems at baseline in the ADHD group predicted variance in diagnostic status. CONCLUSION: Lower-order neuropsychological functions related to motor function and perception are important long-time predictors of persistence of ADHD.

The impact of comorbid spinal pain in depression on work participation and clinical remission following brief or short psychotherapy. Secondary analysis of a randomized controlled trial with two-year follow-up.

OBJECTIVES: This explorative study analyses the influence of baseline comorbid long-lasting spinal pain (CSP) on improvement of long term work participation and clinical remission of mental health illness following either brief coping-focussed or short-term psychotherapy for depression. Whether type of treatment modifies outcome with or without CSP is also analysed. DESIGN: A secondary post hoc subgroup analysis of a pragmatic randomised controlled trial. INTERVENTIONS: Brief or standard short psychotherapy. METHODS: Based on baseline assessment, the sample was subdivided into a subgroup with and a subgroup without CSP. Work participation and clinical remission of depression and anxiety were assessed as treatment outcome at two-year follow-up. Simple and multivariate logistic regression analyses, across the intervention arms, were applied to evaluate the impact of CSP on treatment outcome. Selected baseline variables were considered as potential confounders and included as variates if relevant. The modifying effect of CSP on treatment outcome was evaluated by including intervention modality as an interaction term. MAIN RESULTS: Among the 236 participants with depressive symptoms, 83 participants (35%) were identified with CSP. In simple logistic regression analysis, CSP reduced improvements on both work participation and clinical remission rate. In the multivariate analysis however, the impact of CSP on work participation and on clinical remission were not significant after adjusting for confounding variables. Reduction of work participation was mainly explained by the higher age of the CSP participants and the reduced clinical remission by the additional co-occurrence of anxiety symptoms at baseline. The occurrence of CSP at baseline did not modify long term outcome of brief compared to short psychotherapy. CONCLUSIONS: CSP at baseline reduced work participation and worsened remission of mental health symptoms two-year following psychotherapy. Older age and more severe baseline anxiety are associated to reduced effectiveness. Type of psychotherapy received did not contribute to differences.

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].

Feasibility and Acceptability of a Complex Telerehabilitation Intervention for Pediatric Acquired Brain Injury: The Child in Context Intervention (CICI).

The current study is a feasibility study of a randomized controlled trial (RCT): the Child in Context Intervention (CICI). The CICI study is an individualized, goal-oriented and home-based intervention conducted mainly through videoconference. It targets children with ongoing challenges (physical, cognitive, behavioral, social and/or psychological) after acquired brain injury (ABI) and their families at least one year post injury. The CICI feasibility study included six children aged 11-16 years with verified ABI-diagnosis, their families and their schools. The aim was to evaluate the feasibility of the intervention components, child and parent perceptions of usefulness and relevance of the intervention as well as the assessment protocol through a priori defined criteria. Overall, the families and therapists rated the intervention as feasible and acceptable, including the videoconference treatment delivery. However, the burden of assessment was too high. The SMART-goal approach was rated as useful, and goal attainment was high. The parents' ratings of acceptability of the intervention were somewhat higher than the children's. In conclusion, the CICI protocol proved feasible and acceptable to families, schools and therapists. The assessment burden was reduced, and adjustments in primary outcomes were made for the definitive RCT.

Rehabilitation for children with chronic acquired brain injury in the Child in Context Intervention (CICI) study: study protocol for a randomized controlled trial.

BACKGROUND: Pediatric acquired brain injury (pABI) is associated with long-term cognitive, behavioral, social, and emotional problems, which may affect the quality of life, school, and family functioning. Yet, there is a lack of evidence-based community-centered rehabilitation programs for chronic pABI and these children do not systematically receive comprehensive rehabilitation. The Child In Context Intervention (CICI) study is a pragmatic randomized controlled trial (RCT) for children with chronic pABI, which aims to evaluate the effectiveness of an individualized and goal-oriented intervention targeting everyday functioning of the child and family. METHODS: Children aged 6-16 years with MRI/CT-verified intracranial abnormalities will be included in the CICI study if they have persistent self- or parent-reported cognitive, emotional, and/or behavioral challenges 1 year or more after insult and attend school regularly. A total of 70 families will be randomized 1:1 to an intervention or a control group. The intervention consists of seven family sessions, one parent seminar, and four school sessions delivered over approximately 6 months. The parent seminar will be held in person, and the other sessions will mainly be video based. The children's and families' self-reported major challenges in everyday life will be targeted using SMART goals. Evidence-based strategies, when available, will be applied to achieve the goals, combined with psychoeducation. Goal attainment scaling (GAS) will be used to evaluate goal attainment. Data is collected at baseline and after approximately 6 and 9 months. External assessors are blinded to group allocation. Primary outcomes are parent-reported brain injury symptoms in children and parenting self-efficacy at 9 months of follow-up. Secondary outcomes include child-reported brain injury symptoms, quality of life, executive functioning in daily life, parent emotional symptoms, family functioning, and unmet family health care needs. A process evaluation will be conducted. DISCUSSION: The current study provides an innovative approach to rehabilitation for children in the chronic phase of ABI and their families. This complex intervention may contribute to the development of evidence-based, high-quality rehabilitation for a large patient group, which is underrepresented in clinical research. It may also improve collaboration between specialized rehabilitation facilities, schools, and local health care services. Inclusion for the trial started in April 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04798859 . Registered on March 15, 2021.

Offering alphabet support in the Trail Making Test: Increasing validity for participants with insufficient automatization of the alphabet.

Insufficient automatization of the alphabet may falsely impair performance on the Trail Making Test among persons with dyslexia or persons not accustomed to the Latin alphabet. We analyze whether writing the alphabet on top of the test sheet changes performance in these risk groups, and whether alphabet support reduces the complexity of the set-shifting task.One-hundred and seventy patients referred to neuropsychological assessment participated and were given both a TMT-version offering alphabet support and the D-KEFS TMT. The discrepancy between the D-KEFS subtask where lines are drawn successively between numbers only, and the task where lines are drawn between letters only, was operationalized as measuring insufficient alphabet automatization.Both the possible dyslexia group, and persons taught to read with another alphabet, had a larger discrepancy score than the remaining sample. Regression analyses showed that the discrepancy scores explained 3.4% of the variance beyond age and speed when giving alphabet support. The corresponding percentage for the D-KEFS Switching task was 17.5%. The findings indicate that alphabet support alleviated effects of non-automatization. The TMT-B-NR: TMT-A ratio score was equivalent to what is found when not applying alphabet support, showing that alphabet support did not contaminate the test as a EF-measure.

Factor structure of the new Scandinavian WISC-V version: Support for a five-factor model.

The fifth version of Wechsler Intelligence Scale for Children is designed to measure five distinct aspects of intelligence, incorporating a new fluid reasoning index to the four indexes of the previous fourth version. Several factor analyses, however, have failed to support the fifth factor. The Scandinavian version is the only national version not showing clear superiority for the five-factor solution in the Manual. In the present study, we analyze WISC-V protocols from a clinical sample of 237 children tested with the new Scandinavian version. We perform six confirmatory factor analyses (CFA) testing three hierarchical-, two bifactor-, and one correlated candidate factor models. The study shows that the three-factor model does not fit the data, and that all four- and five-factor models showed good fit. The four-factor bifactor model was somewhat better than the five-bifactor and hierarchical models, but the correlated five-factor model was the superior model. Finding support for five-factors in a clinical sample representative of those most probable to be tested with the test, strengthen the claim that also the Scandinavian version measure a distinct fluid factor as intended by the test owners, and thus that clinicians may use the index scores as their main level of analysis. Review of previous CFAs show that the choice of statistical methods for CFA, bifactor or hierarchical/correlated, influence whether second order factor models are better than g-factor models.

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.

Following H.N. over 21 years: recency change and reduced retention predict later impairment in memory, and recency ratio may combine both effects.

The study follows an intellectually superior patient from initial subjective memory complaints to MCI and dementia over 21 years. Primary memory measures, process- and reliable change-measures from 12 assessments with the California Verbal Learning Test (CVLT) were analyzed as well as experimental measures of retrieval and Recency-Ratio (Rr) combining traditional recency measures with selective retrieval impairments of recency items.Recency change preceded normatively impaired memory by four years, and retention percentage by two years. Rr indicated risk for MCI conversion 13 years prior to receiving that diagnosis, and is an interesting measure for early detection of dementia in CVLT.

Individual Variability in Reaction Time and Prediction of Clinical Response to Methylphenidate in Adult ADHD: A Prospective Open Label Study Using Conners' Continuous Performance Test II.

Objective: The aim of this study was to examine whether reaction time parameters in adult patients with ADHD could predict their response to methylphenidate (MPH). Method: Previously unmedicated patients (N = 123) were administered the Conners' Continuous Performance Test II (CPT II) at baseline and after 6 weeks of treatment with immediate-release MPH. In addition to traditional CPT measures, we extracted intraindividual raw data and analyzed time series using linear and nonlinear mathematical models. Results: Clinical responders, assessed with the Clinical Global Impression-Improvement scale, showed significant normalization of target failures, reduced variability and skewness, and increased complexity of reaction time series after 6 weeks of treatment, while nonresponders showed no significant changes. Prior to treatment, responders had significantly higher variability and skewness, combined with lower complexity, compared with nonresponders. Conclusion: These results show that the CPT test is useful in the evaluation of treatment response to MPH.

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.

Effect of high-intensity interval training on cardiorespiratory fitness, physical activity and body composition in people with schizophrenia: a randomized controlled trial.

BACKGROUND: Exercise may improve cardiorespiratory fitness in people with schizophrenia, however, possible condition-specific cardiorespiratory disadvantages, a scarcity of methodologically sound studies, and conflicting results raise questions about the effect of exercise on maximal oxygen uptake (VO2max) in this group. The primary aim of this study, therefore, was to investigate the effect of high-intensity interval training on VO2max in people with schizophrenia. Second, we sought to determine whether the intervention would have an effect on general physical activity (PA) level and body composition. METHODS: Eighty-two patients with schizophrenia were randomly assigned to supervised high-intensity interval training or computer gaming skills training, performed twice a week for 12 weeks. Oxygen uptake was measured directly, during a maximum exercise session on a treadmill. PA level were assessed using ActiGraph accelerometer, and body composition was assessed by bioelectrical impedance. Differences between groups were assessed by analysis of variance using a univariate general linear model. RESULTS: There were no significant differences between the groups on any of the cardiorespiratory variables neither at baseline nor after the program. There were also no significant within-group differences in any of the cardiorespiratory fitness variables between the baseline and post-program time points, despite that 61% of the participants performing high-intensity interval training showed a significant increase in workload on the treadmill. However, 47% of the participants in the high-intensity interval training group had a ≥ 5% increase in VO2max. Participants supervised by mental health care providers with PA competence (e.g. rehabilitation center staff, sport scientist, physical trainer) had a much larger increase in VO2max compared to participants supervised by mental health workers without such competence, and when adding PA competence to the model, the intervention group increased VO2max significantly compared to the comparison group. The intervention had no significant effect on PA level or body composition. CONCLUSIONS: The intervention did not improve VO2max, PA level or body composition but succeeded in increasing workload on the treadmill. With regard to VO2max, approximately half of the patients may be considered responders. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT02205684 , registered July 2014.

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.