Gry Bang-Kittilsen

• Bang-Kittilsen, Gry; Egeland, Jens; Ueland, Thor; Andersen, Eivind; Bigseth, Therese Torgersen & Holmen, Tom Langerud [Show all 9 contributors for this article] (2023). The relationship between the brain-derived neurotrophic factor and neurocognitive response to physical exercise in individuals with schizophrenia. Psychoneuroendocrinology. ISSN 0306-4530. 157. doi: 10.1016/j.psyneuen.2023.106356. Show summary

  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 VO 2 max 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 VO 2 max 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.

• Bigseth, Therese Torgersen; Engh, John Bjarne Abel; Andersen, Eivind; Bang-Kittilsen, Gry; Egeland, Jens & Falk, Ragnhild Sørum [Show all 12 contributors for this article] (2023). Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia—a randomized controlled trial. Frontiers in Psychiatry. ISSN 1664-0640. 14. doi: 10.3389/fpsyt.2023.1175171. Full text in Research Archive Show summary

  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.

• Bang-Kittilsen, Gry; Engh, John; Holst, Rene; Holmen, Tom Langerud; Bigseth, Therese Torgersen & Andersen, Eivind [Show all 8 contributors for this article] (2022). High-intensity interval training may reduce depressive symptoms in individuals with schizophrenia, putatively through improved VO 2 max: A randomized controlled trial. Frontiers in Psychiatry. ISSN 1664-0640. 13, p. 1–15. doi: 10.3389/fpsyt.2022.921689. Show summary

  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.

• Bigseth, Therese Torgersen; Engh, John; Egeland, Jens; Andersen, Eivind; Andreassen, Ole & Bang-Kittilsen, Gry [Show all 15 contributors for this article] (2021). Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms. BMC Psychiatry. ISSN 1471-244X. 21(1), p. 1–10. doi: 10.1186/s12888-021-03522-6. Full text in Research Archive Show summary

  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.

• Bigseth, Therese Torgersen; Fredriksen, Mats; Egeland, Jens; Andersen, Eivind; Andreassen, Ole Andreas & Bang-Kittilsen, Gry [Show all 15 contributors for this article] (2021). Elevated levels of soluble urokinase plasminogen activator receptor as a low-grade inflammation marker in schizophrenia: A case-control study. Schizophrenia Research. ISSN 0920-9964. 228, p. 190–192. doi: 10.1016/j.schres.2020.11.051.
• Bang-Kittilsen, Gry; Egeland, Jens; Holmen, Tom Langerud; Bigseth, Therese Torgersen; Andersen, Eivind & Mordal, Jon [Show all 8 contributors for this article] (2020). High-intensity interval training and active video gaming improve neurocognition in schizophrenia: a randomized controlled trial. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. 271(2), p. 339–353. doi: 10.1007/s00406-020-01200-4. Show summary

  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

• Andersen, Eivind; Bang-Kittilsen, Gry; Bigseth, Therese Torgersen; Egeland, Jens; Holmen, Tom Langerud & Martinsen, Egil Wilhelm [Show all 8 contributors for this article] (2020). Effect of high-intensity interval training on cardiorespiratory fitness, physical activity and body composition in people with schizophrenia: a randomized controlled trial. BMC Psychiatry. ISSN 1471-244X. 20, p. 1–12. doi: 10.1186/s12888-020-02827-2. Full text in Research Archive Show summary

  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.

• Holmen, Tom Langerud; Egeland, Jens; Andersen, Eivind; Mordal, Jon; Andreassen, Ole Andreas & Ueland, Thor [Show all 9 contributors for this article] (2019). 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. Frontiers in Psychiatry. ISSN 1664-0640. 10:785, p. 1–7. doi: 10.3389/fpsyt.2019.00785. Full text in Research Archive Show summary

  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.

• Engh, John; Egeland, Jens; Andreassen, Ole Andreas; Bang-Kittilsen, Gry; Bigseth, Therese Torgersen & Holmen, Tom Langerud [Show all 9 contributors for this article] (2019). 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. Frontiers in Psychiatry. ISSN 1664-0640. 10. doi: 10.3389/fpsyt.2019.00082. Full text in Research Archive
• Egeland, Jens; Holmen, Tom Langerud; Bang-Kittilsen, Gry; Bigseth, Therese Torgersen; Vaskinn, Anja & Engh, John (2019). Body language reading of emotion and outcome in schizophrenia. Cognitive Neuropsychiatry. ISSN 1354-6805. 24(1), p. 54–64. doi: 10.1080/13546805.2019.1568234. Full text in Research Archive
• Holmen, Tom Langerud; Engh, John; Andersen, Eivind; Andreassen, Ole Andreas; Martinsen, Egil Wilhelm & Bigseth, Therese Torgersen [Show all 8 contributors for this article] (2018). Cardio-respiratory fitness is associated with a verbal factor across cognitive domains in schizophrenia. Schizophrenia Research. ISSN 0920-9964. doi: 10.1016/j.schres.2018.11.033. Full text in Research Archive Show summary

  Abstract Objective We investigated whether the relationship between cardio-respiratory fitness (CRF) and cognition in schizophrenia is general, or due to selective relationships between CRF and specific aspects of cognitive function. Method Eighty outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale version 4 General Ability Index (WAIS GAI), the MATRICS Consensus Cognitive Battery (MCCB) and the Emotion in Biological Motion (EBM) test. CRF was assessed with peak oxygen uptake measured directly during maximum exercise using a modified Balke protocol. Partial correlations, controlling for sex and age, were obtained for the perceptual and the verbal indices of WAIS GAI, six cognitive domains of MCCB, and the EBM total score. A factor analysis was conducted on all 15 subtests of the WAIS GAI and the MCCB, and the factors were subjected to separate regression analyses with CRF as predictor. Results Significant, moderately sized correlations were found between CRF and all cognitive domains except processing speed. The correlation appeared strongest for CRF and the Verbal Comprehension Index of WAIS GAI (r = 0.29, p = .005). The factor analysis identified three factors: one speed/attention/executive function factor, one verbal factor, and one perceptual factor. Regression analyses showed that VO2peak explained a significant amount of variance in the verbal factor only (R2 = 0.06, β = 0.329, p = .03). Conclusion The results indicate that the relationship between CRF and cognition in schizophrenia is selectively tied to a modality-specific association with verbal cognitive abilities. These findings have implications for understanding the relation between cognitive factors and physical health in schizophrenia.

• Andersen, Eivind; Holmen, Tom Langerud; Egeland, Jens; Martinsen, Egil Wilhelm; Bigseth, Therese Torgersen & Bang-Kittilsen, Gry [Show all 9 contributors for this article] (2018). Physical activity pattern and cardiorespiratory fitness in individuals with schizophrenia compared with a population-based sample. Schizophrenia Research. ISSN 0920-9964. doi: 10.1016/j.schres.2018.05.038. Full text in Research Archive Show summary

  Objective: Thorough description of objectively assessed physical activity (PA) and sedentary time in people with schizophrenia is lacking, and previous studies comparing PA and cardiorespiratory fitness levels with healthy controls are limited by their small sample size and/or poor methodology. Method: PA, sedentary behavior, and cardiorespiratory fitness level were assessed in 67 adults diagnosed with schizophrenia (EPHAPS study) and compared with a population-based sample of 2809 adults (NPASS study). Results: Fifty-five percent of the participants with schizophrenia had the unhealthy combination of not meeting the PA recommendations and sitting >7.5 h per day compared to 32% in the population-based sample. The PA level was especially low on weekday afternoons and evenings and throughout most of the day on weekends. The peak oxygen uptake for EPHAPS women was on average 23% lower than that for NPASS women, while EPHAPS men achieved on average 34% lower oxygen uptake on the exercise test compared with NPASS men. Conclusion: People with schizophrenia are significantly less physically active, more sedentary, and have a poorer cardiorespiratory fitness level compared with the general population. Tailor-made PA interventions for people with schizophrenia should target their PA and sedentary behavior on afternoons and weekends especially.

• Egeland, Jens; Holmen, Tom Langerud; Bang-Kittilsen, Gry; Bigseth, Therese Torgersen & Engh, John (2018). Category fluency in schizophrenia: opposing effects of negative and positive symptoms? Cognitive Neuropsychiatry. ISSN 1354-6805. 23(1), p. 28–42. doi: 10.1080/13546805.2017.1418306.

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• Bang-Kittilsen, Gry; Egeland, Jens; Holmen, Tom Langerud; Andersen, Eivind; Ulleberg, Pål & Bigseth, Therese Torgersen [Show all 8 contributors for this article] (2020). Shared and differential neurocognitive effects comparing high-intensity interval training and active video-gaming in schizophrenia - results from an rct. Schizophrenia Bulletin. ISSN 0586-7614. 46, p. S9–S9.

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