Vegard Bruun Bratholm Wyller

• Nyengaard, Rebecca; Kallesøe, Karen Hansen; Rimvall, Martin Køster; Ørnbøl, Eva; Wellnitz, Kaare Bro & Olsen, Else Marie [Show all 8 contributors for this article] (2024). Hair cortisol and self-perceived stress in adolescents with multi-system functional somatic disorders. BMC Psychiatry. ISSN 1471-244X. 24(1). doi: 10.1186/s12888-024-05518-4.
• Sommen, Silke Lauren; Zhao, Zhi; Segtnan, Sunniva; Stiansen-Sonerud, Tonje; Selvakumar, Joel Pradeepkumar & Havdal, Lise Beier [Show all 9 contributors for this article] (2024). Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults. Journal of Translational Medicine. ISSN 1479-5876. 22(1). doi: 10.1186/s12967-024-05117-7.
• Havdal, Lise Beier; Selvakumar, Joel Pradeepkumar; Lund-Berven, Lise; Stiansen-Sonerud, Tonje; Zetterberg, Henrik & Blennow, Kaj [Show all 8 contributors for this article] (2024). Neurological involvement among non-hospitalized adolescents and young adults 6 months after acute COVID-19. Frontiers in Neurology. ISSN 1664-2295. 15. doi: 10.3389/fneur.2024.1345787.
• Christensen, Anders Haugom; Wyller, Vegard Bruun Bratholm; Nygaard, Sissel; Rolid, Katrine; Nytrøen, Kari & Gullestad, Lars [Show all 10 contributors for this article] (2023). Factors Associated with Sinoatrial Reinnervation after Heart Transplantation. Transplantation direct. ISSN 2373-8731. 9(12). doi: 10.1097/TXD.0000000000001553. Full text in Research Archive
• Fløtten, Kjersti Johanne Østrem; Aujoulat, Isabelle; Wyller, Vegard Bruun Bratholm & Solevåg, Anne Lee (2023). “I can’t pose a whole heap of questions that I know I don’t have time to follow up”—Exploring perceptions of an adolescent transition program. PLOS ONE. ISSN 1932-6203. 18(11). doi: 10.1371/journal.pone.0293947. Full text in Research Archive
• Alme, Tomas Nordheim; Andreasson, Anna; Asprusten, Tarjei Tørre; Bakken, Anne Karen; Beadsworth, Michael BJ & Boye, Birgitte [Show all 51 contributors for this article] (2023). Chronic fatigue syndromes: real illnesses that people can recover from. Scandinavian Journal of Primary Health Care. ISSN 0281-3432. 41(4), p. 372–376. doi: 10.1080/02813432.2023.2235609. Full text in Research Archive Show summary

  The ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

• White, Peter; Abbey, Susan; Angus, Brian; Ball, Harriet A; Buchwald, Dedra S & Burness, Christine [Show all 51 contributors for this article] (2023). Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 94(12), p. 1056–1063. doi: 10.1136/jnnp-2022-330463.
• Selvakumar, Joel Pradeepkumar; Havdal, Lise Beier; Drevvatne, Martin Solstrand; Brodwall, Elias Myrstad; Lund-Berven, Lise & Stiansen-Sonerud, Tonje [Show all 19 contributors for this article] (2023). Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults. JAMA Network Open. ISSN 2574-3805. 6(3). doi: 10.1001/jamanetworkopen.2023.5763. Full text in Research Archive
• Sommen, Silke Lauren; Havdal, Lise Beier; Selvakumar, Joel Pradeepkumar; Einvik, Gunnar; Leegaard, Truls Michael & Lund-Johansen, Fridtjof [Show all 12 contributors for this article] (2022). Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19. Frontiers in Immunology. ISSN 1664-3224. 13, p. 1–12. doi: 10.3389/fimmu.2022.1081718. Full text in Research Archive
• Fløtten, Kjersti Johanne Østrem; Aujoulat, Isabelle; Wyller, Vegard Bruun Bratholm & Solevåg, Anne Lee (2022). But what do we mean by “health”? A critical perspective on the concept of health in the adolescent transition program of a Norwegian university hospital. BMC Health Services Research. ISSN 1472-6963. 22(1), p. 1–9. doi: 10.1186/s12913-022-08903-5. Full text in Research Archive
• Nygaard, Sissel; Christensen, Anders Haugom; Sletner, Line; Rolid, Katrine; Nytrøen, Kari & Gullestad, Lars [Show all 11 contributors for this article] (2022). Predictors of Hypertension Development 1 Year after Heart Transplantation. Transplantation. ISSN 0041-1337. 106(8), p. 1656–1665. doi: 10.1097/TP.0000000000004068.
• Øie, Merete Glenne; Buer, Sofie; Sletten Bølgen, Maria; Pedersen, Maria; Asprusten, Tarjei Tørre & Wyller, Vegard Bruun Bratholm (2022). Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection. Journal of Psychosomatic Research. ISSN 0022-3999. 163, p. 1–6. doi: 10.1016/j.jpsychores.2022.111063. Full text in Research Archive
• Havdal, Lise Beier; Berven, Lise; Selvakumar, Joel Pradeepkumar; Stiansen-Sonerud, Tonje; Leegaard, Truls Michael & Tjade, Trygve Olav [Show all 9 contributors for this article] (2022). Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults. Frontiers in Neurology. ISSN 1664-2295. 13. doi: 10.3389/fneur.2022.915712. Full text in Research Archive
• Berven, Lise; Selvakumar, Joel Pradeepkumar; Havdal, Lise Beier; Stiansen-Sonerud, Tonje; Einvik, Gunnar & Leegaard, Truls Michael [Show all 10 contributors for this article] (2022). Inflammatory Markers, Pulmonary Function, and Clinical Symptoms in Acute COVID-19 Among Non-Hospitalized Adolescents and Young Adults. Frontiers in Immunology. ISSN 1664-3224. 13:837288, p. 1–11. doi: 10.3389/fimmu.2022.837288. Full text in Research Archive
• Fevang, Børre; Wyller, Vegard Bruun Bratholm; Mollnes, Tom Eirik; Pedersen, Maria; Asprusten, Tarjei Tørre & Michelsen, Annika Elisabet [Show all 8 contributors for this article] (2021). Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue. Frontiers in Immunology. ISSN 1664-3224. 12. doi: 10.3389/fimmu.2021.715102. Full text in Research Archive
• Christensen, Anders Haugom; Nygaard, Sissel; Rolid, Katrine; Nytrøen, Kari; Gullestad, Lars & Fiane, Arnt Eltvedt [Show all 10 contributors for this article] (2021). Strong evidence for parasympathetic sinoatrial reinnervation after heart transplantation. The Journal of Heart and Lung Transplantation. ISSN 1053-2498. p. 1–12. doi: 10.1016/j.healun.2021.11.005. Full text in Research Archive
• Sandler, Carolina X; Wyller, Vegard B. B; Moss-Morris, Rona; Buchwald, Dedra; Crawley, Esther & Hautvast, Jeannine [Show all 12 contributors for this article] (2021). Long COVID and post-infective fatigue syndrome: A review. Open Forum Infectious Diseases. ISSN 2328-8957. 8(10). doi: 10.1093/ofid/ofab440. Full text in Research Archive Show summary

  Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed “long-COVID”), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16–20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%–35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.

• Christensen, Anders Haugom; Nygaard, Sissel Irene; Rolid, Katrine; Nytrøen, Kari; Gullestad, Lars & Fiane, Arnt [Show all 10 contributors for this article] (2021). Early Signs of Sinoatrial Reinnervation in the Transplanted Heart. Transplantation. ISSN 0041-1337. 105(9), p. 2086–2096. doi: 10.1097/TP.0000000000003580.
• Asprusten, Tarjei Tørre; Sletner, Line & Wyller, Vegard Bruun Bratholm (2021). Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. Journal of Translational Medicine. ISSN 1479-5876. 19, p. 1–12. doi: 10.1186/s12967-021-02713-9. Full text in Research Archive
• Wyller, Vegard Bruun Bratholm; Nygaard, Sissel; Christensen, Anders Haugom; Rolid, Katrine; Nytrøen, Kari & Gullestad, Lars [Show all 10 contributors for this article] (2021). Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation. European Journal of Applied Physiology. ISSN 1439-6319. 121(3), p. 915–927. doi: 10.1007/s00421-020-04586-0. Full text in Research Archive
• Malik, Sadaf; Asprusten, Tarjei Tørre; Pedersen, Maria; Mangersnes, Julie; Trondalen, Gro & Van Roy, Betty [Show all 8 contributors for this article] (2020). Cognitive–behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a randomised controlled trial. BMJ Paediatrics Open. ISSN 2399-9772. 4:e000797, p. 1–10. doi: 10.1136/bmjpo-2020-000797. Full text in Research Archive Show summary

  Abstract Background Cognitive–behavioural therapy (CBT) is effective in chronic fatigue (CF) syndrome. However, CBT has not been investigated in postinfectious CF, nor is it known whether addition of therapeutic elements from other disciplines might be useful. We explored combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents. Methods Adolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months. Power analyses suggested that 120 participants would be needed in order to detect a moderate effect size. Results A total of 91 individuals with postinfectious CF were eligible, and a total of 43 were included (21 intervention group, 22 control group). Concern regarding school absence due to therapy sessions was the main reason for declining participation. Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, the primary endpoint (number of steps/day) did not differ significantly between the intervention group and the control group (difference (95% CI) =–1298 (–4874 to 2278)). Secondary outcome measures were also not significantly different among the two groups. Conclusion An intervention study of combined CBT and music therapy in postinfectious CF is feasible. A fully powered trial is needed to evaluate efficacy; participants’ concern regarding school absence should be properly addressed to secure recruitment. Trial registration number ClinicalTrials ID: NCT02499302, registered July 2015. http://dx.doi.org/10.1136/bmjpo-2020-000797

• Brodwall, Elias Myrstad; Pedersen, Maria; Asprusten, Tarjei Tørre & Wyller, Vegard Bruun Bratholm (2020). Pain in adolescent chronic fatigue following Epstein-Barr virus infection. Scandinavian Journal of Pain. ISSN 1877-8860. doi: 10.1515/sjpain-2020-0031.
• Trondalen, Gro; Mangersnes, Julie; Bonde, Lars Ole; Malik, Sadaf; Asprusten, Tarjei Tørre & Rødevand, Linn Nilsen [Show all 8 contributors for this article] (2020). Music therapy for chronic fatigue following epstein-barr virus infection in adolescents. Music and Medicine. ISSN 1943-863X. 12(2), p. 84–91. doi: 10.47513/mmd.v12i2.679.
• Nygaard, Sissel Irene; Christensen, Anders Haugom; Rolid, Katrine; Nytrøen, Kari; Gullestad, Lars & Fiane, Arnt E [Show all 11 contributors for this article] (2019). Autonomic cardiovascular control changes in recent heart transplant recipients lead to physiological limitations in response to orthostatic challenge and isometric exercise. European Journal of Applied Physiology. ISSN 1439-6319. 119(10), p. 2225–2236. doi: 10.1007/s00421-019-04207-5. Full text in Research Archive
• Asprusten, Tarjei Tørre; Pedersen, Maria; Skovlund, Eva & Wyller, Vegard Bruun Bratholm (2019). EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection. BMJ Paediatrics Open. ISSN 2399-9772. 3(1). doi: 10.1136/bmjpo-2018-000390. Full text in Research Archive
• Hov, Karen Roksund; Neerland, Bjørn Erik; Undseth, Øystein; Wyller, Vegard Bruun Bratholm; MacLullich, Alasdair M.J. & Qvigstad, Eirik [Show all 8 contributors for this article] (2019). The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. International Journal of Geriatric Psychiatry. ISSN 0885-6230. 34(7), p. 974–981. doi: 10.1002/gps.5098. Full text in Research Archive
• Kristiansen, Miriam Skjerven; Stabursvik, Julie; O'Leary, Elise Catriona Solberg; Pedersen, Maria; Asprusten, Tarjei Tørre & Leegaard, Truls Michael [Show all 11 contributors for this article] (2019). Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study. Brain, Behavior, and Immunity. ISSN 0889-1591. 80, p. 551–563. doi: 10.1016/j.bbi.2019.04.040. Full text in Research Archive
• Neerland, Bjørn Erik; Wyller, Torgeir Bruun & Wyller, Vegard Bruun Bratholm (2019). Autonomic cardiovascular control in older patients with acute infection and delirium: a pilot study of orthostatic stress responses. BMC Geriatrics. ISSN 1471-2318. 19(23), p. 1–8. doi: 10.1186/s12877-019-1035-0. Full text in Research Archive
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N. & Skovlund, Eva [Show all 9 contributors for this article] (2019). Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study. Journal of Psychosomatic Research. ISSN 0022-3999. 121, p. 46–59. doi: 10.1016/j.jpsychores.2019.04.008.
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N. & Skovlund, Eva [Show all 9 contributors for this article] (2019). Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later. Acta Paediatrica. ISSN 0803-5253. 108(8), p. 1521–1526. doi: 10.1111/apa.14728. Full text in Research Archive
• Nguyen, Chinh BKrong; Kumar, Surendra; Zucknick, Manuela; Kristensen, Vessela N.; Gjerstad, Johannes & Nilsen, Hilde Loge [Show all 7 contributors for this article] (2019). Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome. Brain, Behavior, and Immunity. ISSN 0889-1591. 76, p. 82–96. doi: 10.1016/j.bbi.2018.11.008. Full text in Research Archive Show summary

  Background Chronic Fatigue Syndrome (CFS) is one of the most important causes of disability among adolescents while limited knowledge exists on genetic determinants underlying disease pathophysiology. Methods We analyzed deregulated immune-gene modules using Pathifier software on whole blood gene expression data (29 CFS patients, 18 controls). Deconvolution of immune cell subtypes based on gene expression profile was performed using CIBERSORT. Supervised consensus clustering on pathway deregulation score (PDS) was used to define CFS subgroups. Associations between PDS and immune, neuroendocrine/autonomic and clinical markers were examined. The impact of plasma norepinephrine level on clinical markers over time was assessed in a larger cohort (91 patients). Results A group of 29 immune-gene sets was shown to differ patients from controls and detect subgroups within CFS. Group 1P (high PDS, low norepinephrine, low naïve CD4+ composition) had strong association with levels of serum C-reactive protein and Transforming Growth Factor-beta. Group 2P (low PDS, high norepinephrine, high naïve CD4+ composition) had strong associations with neuroendocrine/autonomic markers. The corresponding plasma norepinephrine level delineated 91 patients into two subgroups with significant differences in fatigue score. Conclusion We identified 29 immune-gene sets linked to plasma norepinephrine level that could delineate CFS subgroups. Plasma norepinephrine stratification revealed that lower levels of norepinephrine were associated with higher fatigue. Our data suggests potential involvement of neuro-immune dysregulation and genetic stratification in CFS.

• Katz, Ben Z; Collin, Simon M.; Murphy, Gabrielle; Moss-Morris, Rona; Wyller, Vegard Bruun Bratholm & Wensaas, Knut-Arne [Show all 15 contributors for this article] (2018). The international collaborative on fatigue following infection (COFFI). Fatigue: Biomedicine, Health & Behavior. ISSN 2164-1846. 6(2), p. 106–121. doi: 10.1080/21641846.2018.1426086.
• Valenza, Gaetano; Citi, Luca; Wyller, Vegard Bruun Bratholm & Barbieri, Riccardo (2018). ECG-derived sympathetic and parasympathetic activity in the healthy: An early lower-body negative pressure study using adaptive Kalman prediction. IEEE Engineering in Medicine and Biology Society. Conference Proceedings. ISSN 1557-170X. 2018:8513512-July, p. 5628–5631. doi: 10.1109/EMBC.2018.8513512.
• Asprusten, Tarjei Tørre; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Skovlund, Eva & Wyller, Vegard Bruun Bratholm (2018). Systemix exertion intolerance disease diagnostic criteria Applied on an adolescent chronic fatigue syndrom cohort: evaluation of subgroup differences and prognostic utility. BMJ Paediatrics Open. ISSN 2399-9772. 2:e000233, p. 1–8. doi: 10.1136/bmjpo-2017-000233. Full text in Research Archive
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N. & Skovlund, Eva [Show all 9 contributors for this article] (2018). Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: a prospective cohort study. Brain, Behavior, and Immunity. ISSN 0889-1591. 75, p. 94–100. doi: 10.1016/j.bbi.2018.09.023. Full text in Research Archive
• Hov, Karen Roksund; Neerland, Bjørn Erik; Andersen, Anders Mikal; Undseth, Øystein; Wyller, Vegard Bruun Bratholm & MacLullich, Alasdair M.J. [Show all 9 contributors for this article] (2018). The use of clonidine in elderly patients with delirium; pharmacokinetics and hemodynamic responses. BMC Pharmacology & Toxicology. ISSN 2050-6511. 19(29). doi: 10.1186/s40360-018-0218-1. Full text in Research Archive
• Wyller, Vegard Bruun Bratholm; Nguyen, Chinh Bkrong Thi Thuy; Ludviksen, Judith K & Mollnes, Tom Eirik (2017). Transforming growth factor beta (TGF‑β)in adolescent chronic fatigue syndrome. Journal of Translational Medicine. ISSN 1479-5876. 15(1). doi: 10.1186/s12967-017-1350-1. Full text in Research Archive
• Wyller, Hedda Bratholm ; Wyller, Vegard Bruun Bratholm; Crane, Catherine & Gjelsvik, Bergliot (2017). The relationship between sensory processing sensitivity and psychological distress: A model of underpinning mechanisms and an analysis of therapeutic possibilities. Scandinavian Psychologist. ISSN 1894-5570. doi: 10.15714/scandpsychol.4.e15.
• Pedersen, Maria; Ekstedt, Mirjam; Småstuen, Milada C; Wyller, Vegard Bruun Bratholm; Sulheim, Dag & Fagermoen, Frode Even [Show all 9 contributors for this article] (2017). Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. Journal of Sleep Research. ISSN 0962-1105. 26(5), p. 595–601. doi: 10.1111/jsr.12547. Show summary

  Chronic fatigue syndrome (CFS) is characterized by long-lasting, disabling and unexplained fatigue that is often accompanied by unrefreshing sleep. The aim of this cross-sectional study was to investigate sleep–wake rhythm and perceived sleep in adolescent CFS patients compared to healthy individuals. We analysed baseline data on 120 adolescent CFS patients and 39 healthy individuals included in the NorCAPITAL project. Activity measures from a uniaxial accelerometer (activPAL) were used to estimate mid-sleep time (mid-point of a period with sleep) and time in bed. Scores from the Karolinska Sleep Questionnaire (KSQ) were also assessed. The activity measures showed that the CFS patients stayed significantly longer in bed, had a significantly delayed mid-sleep time and a more varied sleep–wake rhythm during weekdays compared with healthy individuals. On the KSQ, the CFS patients reported significantly more insomnia symptoms, sleepiness, awakening problems and a longer sleep onset latency than healthy individuals. These results might indicate that disrupted sleep–wake phase could contribute to adolescent CFS; however, further investigations are warranted.

• Wyller, Vegard Bruun Bratholm (2017). The bedside rationing paradigm and the shortcomings of modernist ethics. Clinical Ethics. ISSN 1477-7509. 12(2), p. 70–75. doi: 10.1177/1477750917691888.
• Feiring, Berit; Laake, Ida; Bakken, Inger Johanne; Greve-Isdahl, Margrethe; Wyller, Vegard Bruun Bratholm & Håberg, Siri Eldevik [Show all 8 contributors for this article] (2017). HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine. ISSN 0264-410X. 35(33), p. 4203–4212. doi: 10.1016/j.vaccine.2017.06.031.
• Bakke, Laura A. Wortinger ; Øie, Merete Glenne; Endestad, Tor & Wyller, Vegard Bruun Bratholm (2017). Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome. PLOS ONE. ISSN 1932-6203. 12(9). doi: 10.1371/journal.pone.0184325. Full text in Research Archive Show summary

  Abstract Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants. Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI–PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI–PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.

• Nguyen, Chinh Bkrong Thi Thuy; Alsøe, Lene; Lindvall, Jessica Margareta; Sulheim, Dag; Fagermoen, Frode Even & Winger, Anette [Show all 9 contributors for this article] (2017). Whole blood gene expression in adolescent chronic fatigue syndrome: An exploratory cross-sectional study suggesting altered B cell differentiation and survival. Journal of Translational Medicine. ISSN 1479-5876. 15. doi: 10.1186/s12967-017-1201-0. Full text in Research Archive Show summary

  Background Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. Methods CFS patients (12–18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. Results A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. Conclusion Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise.

• Bakke, Laura A Wortinger; Endestad, Tor; Melinder, Annika Maria D; Øie, Merete Glenne; Sulheim, Dag & Fagermoen, Frode Even [Show all 7 contributors for this article] (2017). Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. Journal of Clinical and Experimental Neuropsychology. ISSN 1380-3395. 39(4), p. 355–368. doi: 10.1080/13803395.2016.1230180. Full text in Research Archive Show summary

  Introduction: Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control. Method: In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words. Results: Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity. Conclusions: These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS.

• Hall, Karhryn T.; Kossowsky, Joe; Oberlander, Tim F.; Kaptchuk, Ted J.; Saul, J. Philip & Wyller, Vegard Bruun [Show all 11 contributors for this article] (2016). Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome. The Pharmacogenomics Journal. ISSN 1470-269X. 16(5), p. 454–460. doi: 10.1038/tpj.2016.53. Full text in Research Archive Show summary

  Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene–drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine–COMT interaction effects in other conditions.

• Bakke, Laura A Wortinger; Endestad, Tor; Melinder, Annika Maria D; Øie, Merete Glenne; Nilsen, Andre Sevenius & Wyller, Vegard Bruun (2016). Aberrant resting-state functional connectivity in the Salience Network of adolescent Chronic Fatigue Syndrome. PLOS ONE. ISSN 1932-6203. 11(7). doi: 10.1371/journal.pone.0159351. Show summary

  Abstract Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

• Wyller, Vegard Bruun; Vitelli, Valeria; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette & Godang, Kristin [Show all 7 contributors for this article] (2016). Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. Journal of Translational Medicine. ISSN 1479-5876. 14(121). doi: 10.1186/s12967-016-0873-1. Full text in Research Archive
• Meyer, Benedicte; Nguyen, Chinh Bkrong Thi Thuy; Moen, Aurora ; Fagermoen, Frode Even; Sulheim, Dag & Nilsen, Hilde [Show all 8 contributors for this article] (2015). Maintenance of Chronic Fatigue Syndrome (CFS) in young CFS patients is associated with the 5-HTTLPR and SNP rs25531 A > G Genotype. PLOS ONE. ISSN 1932-6203. 10(10). doi: 10.1371/journal.pone.0140883. Show summary

  Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12–18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

• Neerland, Bjørn Erik; Hov, Karen Roksund; Wyller, Vegard Bruun; Qvigstad, Eirik; Skovlund, Eva & MacLullich, AM [Show all 7 contributors for this article] (2015). The protocol of the oslo study of clonidine in elderly patients with delirium; LUCID: A randomised placebo-controlled trial. BMC Geriatrics. ISSN 1471-2318. 15:7, p. 1–14. doi: 10.1186/s12877-015-0006-3.
• Asprusten, Tarjei Tørre; Fagermoen, Frode Even; Sulheim, Dag; Skovlund, Eva; Sørensen, Øystein & Mollnes, Tom Eirik [Show all 7 contributors for this article] (2015). Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome. Acta Paediatrica. ISSN 0803-5253. 104(5), p. 498–503. doi: 10.1111/apa.12950.
• Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Andersen, Anders Mikal; Gjerstad, Johannes & Godang, Kristin [Show all 10 contributors for this article] (2015). Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: A randomized controlled trial. BMC Pediatrics. ISSN 1471-2431. 15. doi: 10.1186/s12887-015-0428-2. Full text in Research Archive Show summary

  Background: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A–adrenoceptor agonist clonidine. Methods: A total of 176 adolescent CFS patients (12–18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model. Results: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period. Conclusions: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.

• Winger, Anette; Kvarstein, Gunnvald; Wyller, Vegard Bruun; Ekstedt, Mirjam; Sulheim, Dag & Fagermoen, Frode Even [Show all 8 contributors for this article] (2015). Health related quality of life in adolescents with chronic fatigue syndrome: A cross-sectional study. Health and Quality of Life Outcomes. ISSN 1477-7525. 13:96. doi: 10.1186/s12955-015-0288-3. Full text in Research Archive
• Mellingsæter, Marte; Wyller, Torgeir Bruun; Ranhoff, Anette Hylen; Bogdanovic, Nenad & Wyller, Vegard Bruun (2015). Reduced sympathetic response to head-up tilt in subjects with mild cognitive impairment or mild Alzheimer's dementia. Dementia and Geriatric Cognitive Disorders Extra. ISSN 1664-5464. 5(1), p. 107–115. doi: 10.1159/000375297. Full text in Research Archive
• Sulheim, Dag; Fagermoen, Frode Even; Sivertsen, Øyvind Stople; Winger, Anette; Wyller, Vegard Bruun & Øie, Merete Glenne (2015). Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study. Archives of Disease in Childhood. ISSN 0003-9888. 100(9), p. 838–844. doi: 10.1136/archdischild-2014-306764. Full text in Research Archive
• Wyller, Vegard Bruun; Sørensen, Øystein; Sulheim, Dag; Fagermoen, Frode Even; Ueland, Thor & Mollnes, Tom Eirik (2015). Plasma cytokine expression in adolescent chronic fatigue syndrome. Brain, Behavior, and Immunity. ISSN 0889-1591. 46, p. 80–86. doi: 10.1016/j.bbi.2014.12.025. Show summary

  Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12–18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p < 0.001) and inflammatory symptoms (p < 0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology.

• Mellingsæter, Marte; Wyller, Torgeir Bruun; Ranhoff, Anette Hylen & Wyller, Vegard Bruun (2015). Fit elderly men can also stand: orthostatic tolerance and autonomic cardiovascular control in elderly endurance athletes. Aging Clinical and Experimental Research. ISSN 1594-0667. 27(4), p. 499–505. doi: 10.1007/s40520-014-0303-2.
• Zeller, Bernward; Loge, Jon Håvard; Kanellopoulos, Adriani; Hamre, Hanne Mari; Wyller, Vegard Bruun & Ruud, Ellen (2014). Chronic fatigue in long-term survivors of childhood Lymphomas and Leukemia: Persistence and associated clinical factors. Journal of Pediatric Hematology/Oncology. ISSN 1077-4114. 36(6), p. 438–444. doi: 10.1097/MPH.0000000000000051.
• Winger, Anette; Kvarstein, Gunnvald; Wyller, Vegard Bruun; Sulheim, Dag; Fagermoen, Frode Even & Småstuen, Milada Cvancarova [Show all 7 contributors for this article] (2014). Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. BMJ Open. ISSN 2044-6055. 4(10). doi: 10.1136/bmjopen-2014-005920. Full text in Research Archive Show summary

  Objectives: Although pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC). Methods: This is a case–control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12–18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial. Results: Adolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001). Conclusions: We found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS.

• Wyller, Vegard Bruun; Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Skovlund, Eva & Saul, J. Philip (2014). Orthostatic responses in adolescent chronic fatigue syndrome: Contributions from expectancies as well as gravity. BioPsychoSocial Medicine. ISSN 1751-0759. 8. doi: 10.1186/1751-0759-8-22. Full text in Research Archive Show summary

  Background: Orthostatic intolerance is common in chronic fatigue syndrome (CFS), and several studies have documented an abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli. The aim of this study was to explore whether the expectancies towards standing are contributors to autonomic responses in addition to the gravitational stimulus itself. Methods: A total of 30 CFS patients (12–18 years of age) and 39 healthy controls underwent 20° head-up tilt test and a motor imagery protocol of standing upright. Beat-to-beat cardiovascular variables were recorded. Results: At supine rest, CFS patients had significantly higher heart rate, diastolic blood pressure, and mean arterial blood pressure, and lower stroke index and heart rate variability (HRV) indices. The response to 20° head-up tilt was identical in the two groups. The response to imaginary upright position was characterized by a stronger increase of HRV indices of sympathetic predominance (power in the low-frequency range as well as the ratio low-frequency: high-frequency power) among CFS patients. Conclusions: These results suggest that in CFS patients expectancies towards orthostatic challenge might be additional determinants of autonomic cardiovascular modulation along with the gravitational stimulus per se.

• Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Andersen, Anders Mikal; Godang, Kristin & Müller, Fredrik [Show all 11 contributors for this article] (2014). Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome: A Combined Cross-sectional and Randomized Clinical Trial. JAMA pediatrics. ISSN 2168-6203. 168(4), p. 351–360. doi: 10.1001/jamapediatrics.2013.4647. Full text in Research Archive
• Kristensen, Hanne; Ørbeck, Beate; Torgersen, Halvor; Hansen, Berit Marina Hjelde & Wyller, Vegard Bruun (2014). Somatic symptoms in children with anxiety disorders: an exploratory cross-sectional study of the relationship between subjective and objective measures. European Child and Adolescent Psychiatry. ISSN 1018-8827. 23(9), p. 795–803. doi: 10.1007/s00787-013-0512-9. Show summary

  Symptoms of childhood anxiety disorders include activation of bodily stress systems to fear stimuli, indicating alterations of the autonomic nervous system (ANS). Self-reported somatic symptoms are frequently reported, while studies including objective measures of ANS are scarce and show inconsistent results. Even less studied is the relationship between subjective and objective measures of somatic symptoms in anxious children. Increased knowledge of this relationship may have relevance for treatment programmes for anxiety disorders. This cross-sectional study examined subjective and objective measures of ANS responsiveness in a clinical sample of children with anxiety disorders (7–13 years; n = 23) and in healthy controls (HC; n = 22) with equal distributions of gender and age. The subjective measure used was the Multidimensional Anxiety Scale for Children (MASC), which includes a subscale on somatic symptoms. The objective measures consisted of an orthostatic challenge (head-up tilt test, HUT), and an isometric muscular exercise (handgrip) while the participants were attached to the Task Force Monitor, a combined hardware and software device used for continuous, non-invasive recording of cardiovascular variables. The anxiety disorder group reported significantly more somatic symptoms than HCs (both by mother and child reports). In contrast, no relevant differences in cardiovascular variables were demonstrated between the anxiety group and HCs. Finally, there were no significant correlations between subjective and objective measures in either group. Because of the small sample size, the findings must be interpreted carefully, but the results do not support previous reports of functional alterations of the ANS in anxious children.

• Wyller, Vegard Bruun & Helland, Ingrid B (2013). Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study. BioPsychoSocial Medicine. ISSN 1751-0759. doi: 10.1186/1751-0759-7-5.
• Wyller, Vegard Bruun; Gisvold, Sven Erik; Hagen, Egil Ragnar; Heggedal, Rune; Heimdal, Arnulf & Karlsen, Kjetil [Show all 10 contributors for this article] (2013). Reclaim the profession! Tidsskrift for Den norske legeforening. ISSN 0029-2001. doi: 10.4045/tidsskr.13.0238.
• Winger, Anette; Ekstedt, Mirjam; Wyller, Vegard Bruun & Helseth, Sølvi (2013). Sometimes it feels as if the world goes on without me: adolescents' experiences of living with chronic fatigue syndrome. Journal of Clinical Nursing (JCN). ISSN 0962-1067. doi: 10.1111/jocn.12522. Show summary

  AIMS AND OBJECTIVES: To explore the experience of being an adolescent with chronic fatigue syndrome. BACKGROUND: Despite ample research, chronic fatigue syndrome is still poorly understood, and there are still controversies related to the illness. Adolescents with chronic fatigue syndrome are often unable to attend school and lose social relations with friends. The challenges they face will affect their quality of life. DESIGN: A qualitative, phenomenological hermeneutical design. METHOD: Six boys and twelve girls, aged 12-18, were interviewed, emphasising their own experiences living with chronic fatigue syndrome. Analyses were performed using a phenomenological hermeneutical method. RESULTS: The core theme, 'Sometimes it feels as if the world goes on without me', encompasses the feelings an adolescent living with chronic fatigue syndrome might have about life. The core theme was supported by four subthemes: 'On the side of life - locked in and shut out'; 'the body, the illness and me'; 'if the illness is not visible to others, does it exist?'; and 'handling life while hoping for a better future'. The subthemes reflect the experience of social isolation, their own and others' understanding of the illness and hope for the future. CONCLUSIONS: Not being able to be with friends, or attend school, made the adolescents feel different and forgotten. They felt alienated in their own bodies and were struggling to be visible to themselves and to their surroundings. Spending less time with friends and more time with their parents constituted a threat to independence and development. Yet they managed to envision a better future despite all the difficulties. RELEVANCE FOR CLINICAL PRACTICE: To provide effective support and constructive relations to adolescents with chronic fatigue syndrome, all health professions involved need insight from the persons who are themselves ill. Health centres could function as resource centres for patients and healthcare professionals

• Elsais, Ahmed; Wyller, Vegard Bruun; Loge, Jon Håvard & Kerty, Emilia (2013). Fatigue in myasthenia gravis: is it more than muscular weakness? BMC Neurology. ISSN 1471-2377. 13. doi: 10.1186/1471-2377-13-132. Full text in Research Archive
• Mellingsæter, Marte; Wyller, Vegard Bruun; Wyller, Torgeir Bruun & Ranhoff, Anette Hylen (2013). Gender differences in orthostatic tolerance in the elderly. Aging Clinical and Experimental Research. ISSN 1594-0667. 25(6), p. 659–665. doi: 10.1007/s40520-013-0092-z.
• Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Andersen, Anders Mikal; Vethe, Nils Tore & Saul, J P [Show all 8 contributors for this article] (2012). Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Research Notes. ISSN 1756-0500. 5. doi: 10.1186/1756-0500-5-418. Full text in Research Archive
• Sulheim, Dag; Hurum, Harald; Helland, Ingrid B; Thaulow, Erik & Wyller, Vegard Bruun (2012). Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. BioPsychoSocial Medicine. ISSN 1751-0759. 6. doi: 10.1186/1751-0759-6-10.
• Wyller, Vegard Bruun; Aaberge, Lars; Thaulow, Erik & Døhlen, Gaute (2011). Percutaneous catheter-based implantation of artificial pulmonary valves in patients with congenital heart defects. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 13-14, p. 1289–1293. doi: 10.4045/tidsskr.10.0920. Show summary

  Bakgrunn. Perkutan kateterbasert innsetting av kunstige hjerteklaffer er en ny teknikk som kan få økende utbredelse i fremtiden og supplere kirurgiske inngrep. Vi rapporterer her våre første erfaringer med innsetting av kunstig pulmonalklaff hos barn med medfødt hjertefeil. Materiale og metode. Teknikken vurderes hos pasienter med hjertesviktsymptomer og stenose og/eller insuffisiens i et kunstig utløp fra høyre ventrikkel. Klaffen føres gjennom et kateter fra lyskevene eller halsvene. Behandlingseffekt vurderes ved symptombeskrivelse, ekkokardiografi, invasive målinger og angiografi. Vi rapporterer her våre behandlingsresultater i perioden april 2007 til september 2009. Resultater. Materialet består av ti pasienter (sju menn og tre kvinner, median alder 17 år). Prosedyren reduserte trykket i høyre ventrikkel (p = 0,008) og opphevet pulmonalinsuffisiensen hos alle ti pasienter. Median liggetid var to dager. Det oppsto ingen komplikasjoner med direkte forbindelse til innsettelsesprosedyren, men én pasient utviklet et pseudoaneurisme i a. femoralis, og en annen pasient fikk kortvarig feber to dager etter prosedyren. Hos én pasient måtte klaffen fjernes kirurgisk etter ni måneder pga. stentbrudd. Etter seks måneder rapporterte samtlige pasienter en symptombedring, trykkgradienten i høyre ventrikkel-utløp var redusert (p = 0,008) og pulmonalinsuffisiensen var bedret (p = 0,006). Disse resultatene vedvarte hos de fire pasientene som er blitt undersøkt etter 24 måneder. Fortolkning. Perkutan kateterbasert innsetting av kunstig pulmonalklaff bedrer høyre ventrikkels hemodynamikk hos utvalgte pasienter med medfødt hjertefeil. For sikrere kunnskap bør det imidlertid gjennomføres en randomisert, kontrollert studie.

• Hareide, Live; Finset, Arnstein & Wyller, Vegard Bruun (2011). Chronic fatigue syndrome: a qualitative investigation of young patient's beliefs and coping strategies. Disability and Rehabilitation. ISSN 0963-8288. 33(23-24), p. 2255–2263. doi: 10.3109/09638288.2011.568663.
• Hurum, Harald; Sulheim, Dag; Thaulow, Erik & Wyller, Vegard Bruun (2011). Elevated nocturnal blood pressure and heart rate in adolescent chronic fatigue syndrome. Acta Paediatrica. ISSN 0803-5253. 100(2), p. 289–292. doi: 10.1111/j.1651-2227.2010.02073.x.
• Wyller, Vegard Bruun; Barbieri, Riccardo & Saul, J. Philip (2011). Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress. European Journal of Applied Physiology. ISSN 1439-6319. 111(3), p. 497–507. doi: 10.1007/s00421-010-1670-9.
• Sommerfeldt, Line; Portilla, Helene; Jacobsen, Line Melå; Gjerstad, Johannes & Wyller, Vegard Bruun (2011). Polymorphisms of adrenergic cardiovascular control genes are associated with adolescent chronic fatigue syndrome. Acta Paediatrica. ISSN 0803-5253. 100(2), p. 293–298. doi: 10.1111/j.1651-2227.2010.02072.x. Show summary

  Aim: To explore the frequency of polymorphisms in adrenergic cardiovascular control genes in adolescent with chronic fatigue syndrome (CFS) and the relation of such polymorphisms to cardiovascular variables. Methods: DNA from 53 patients with CFS, 12–18 years old, was analysed for five single nucleotide polymorphisms (SNPs) in the genes catechol‐O‐methyltransferase (COMT), the β2‐adrenergic receptor (two SNPs), the β1‐adrenergic receptor and the α2a‐adrenergic receptor. Frequencies were compared to a reference population constructed from the National Center for Biotechnology Information (NCBI) database, and associations between frequencies and autonomic cardiovascular responses during a 20° head‐uptilt‐test were explored. Results: For the COMT SNP Rs4680, patients with CFS had a higher frequency of the AA genotype and a lower frequency of the G containing genotypes (AG and GG), when compared to the reference sample (p = 0.046). Also, the AA genotype was associated with a smaller increase in LF/HF ratio (low‐frequency:high‐frequency heart rate variability ratio, an index of cardiac sympathovagal balance) during head‐up tilt when compared to the AG/GG genotypes. For the β2‐adrenergic receptor SNP Rs1042714, patients with CFS had a lower frequency of the GG genotype and a higher frequency of the genotypes containing C (CG and CC) (p = 0.044). Conclusions: CFS might be related to polymorphisms of COMT and the β2‐adrenergic receptor. More details of the molecular mechanisms remain to be investigated.

• Wyller, Vegard Bruun; Evang, Johan Arild; Godang, Kristin; Solhjell, Kari Kittang & Bollerslev, Jens (2010). Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatrica. ISSN 0803-5253. 99(5), p. 770–773. doi: 10.1111/j.1651-2227.2010.01701.x.
• Gjone, Helene & Wyller, Vegard Bruun (2009). Chronic fatigue in adolescence-autonomic dysregulation and mental health: an exploratory study. Acta Paediatrica. ISSN 0803-5253. 98(8), p. 1313–1318. doi: 10.1111/j.1651-2227.2009.01323.x.
• Wyller, Vegard Bruun; Saul, JP; Walløe, Lars & Thaulow, E (2008). Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. European Journal of Applied Physiology. ISSN 1439-6319. 102. doi: 10.1007/s00421-007-0634-1.

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• Wyller, Vegard Bruun Bratholm & Hem, Erlend (2023). Failure to thrive = sviktende utvikling. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 143(13). doi: 10.4045/tidsskr.23.0096.
• Verveen, Anouk; Müller, Fabiola; Lloyd, Andrew; Moss-Morris, Rona; Omland, Torbjørn & Penninx, Brenda [Show all 14 contributors for this article] (2022). A research agenda for post-COVID-19 fatigue. Journal of Psychosomatic Research. ISSN 0022-3999. 154. doi: 10.1016/j.jpsychores.2022.110726.
• Nygaard, Sissel Irene; Rolid, Katrine; Nytrøen, Kari; Fiane, Arnt E; Wyller, Vegard Bruun Bratholm & Gullestad, Lars [Show all 7 contributors for this article] (2020). Heart Rate Response after Heart Transplantation. The Journal of Heart and Lung Transplantation. ISSN 1053-2498. 39(4), p. S285–S286. doi: 10.1016/j.healun.2020.01.630.
• Wyller, Vegard Bruun Bratholm (2019). Chronic fatigue is characterized by a relative lack of abnormalities in biological markers. Brain, Behavior, and Immunity. ISSN 0889-1591. 80. doi: 10.1016/j.bbi.2019.05.043.
• Wyller, Vegard Bruun Bratholm (2019). Autonomic and inflammatory disturbances do not seem to explain symptoms in chronic fatigue. Brain, Behavior, and Immunity. ISSN 0889-1591. 80. doi: 10.1016/j.bbi.2019.05.037.
• Wyller, Vegard Bruun Bratholm (2019). Pain is common in chronic fatigue syndrome-current knowledge and future perspectives. Scandinavian Journal of Pain. ISSN 1877-8860. 19(1), p. 5–8. doi: 10.1515/sjpain-2018-2007.
• Nordin, Succora; Donkor, Hilde Mjell; Wyller, Vegard Bruun Bratholm; Farstad, Teresa; Borthne, Arne Sigmund & Moen, Atle [Show all 7 contributors for this article] (2018). Pericarditis in a newborn child. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 138(5). doi: 10.4045/tidsskr.17.0555.
• Bratholm, Hedda & Wyller, Vegard Bruun Bratholm (2018). Feilinformasjon om kronisk utmattelsessyndrom. Tidsskrift for Norsk Psykologforening. ISSN 0332-6470. 55(2), p. 126–127.
• Wyller, Vegard Bruun Bratholm; Vitelli, Valeria; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette & Godang, Kristin [Show all 7 contributors for this article] (2017). Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: A cross-sectional study. Journal of Translational Medicine. ISSN 1479-5876. 15(157). doi: 10.1186/s12967-017-1261-1.
• Wyller, Vegard Bruun Bratholm (2016). Den brysomme samvittigheten. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 136(7), p. 595–595. doi: 10.4045/tidsskr.16.0268.
• Vogt, Henrik; Ulvestad, Elling & Wyller, Vegard Bruun Bratholm (2016). Metabolic features of chronic fatigue syndrome revisited. Proceedings of the National Academy of Sciences of the United States of America. ISSN 0027-8424. 113(46), p. E7140–E7141. doi: 10.1073/pnas.1615143113.
• Wyller, Vegard Bruun; Reme, Silje & Mollnes, Tom Eirik (2016). Kronisk utmattelsessyndrom/myalgisk encefalopati - sykdomsmekanismer, diagnostikk og behandling. Fysioterapeuten. ISSN 0016-3384. 83(2), p. 24–27.
• Wyller, Vegard Bruun; Jacobsen, Kristine; Dahl, Mai Britt; Nilsen, Hilde; Proske, Simone & Horter, Thorsten [Show all 7 contributors for this article] (2016). Interferon gamma may improve cardiac function in Friedreich's ataxia cardiomyopathy. International Journal of Cardiology. ISSN 0167-5273. 221, p. 376–378. doi: 10.1016/j.ijcard.2016.06.288.
• Wyller, Vegard Bruun (2015). Re: Hva er egentlig myalgisk encefalopati? Tidsskrift for Den norske legeforening. ISSN 0029-2001. 135(22), p. 2021–2021. doi: 10.4045/tidsskr.15.1186.
• Wyller, Vegard Bruun (2015). Re: Hva er egentlig myalgisk encefalopati? Tidsskrift for Den norske legeforening. ISSN 0029-2001. 135(22). doi: 10.4045/tidsskr.15.1184.
• Wyller, Vegard Bruun (2015). Helsepolitikk – mer ideologi enn fornuft? :. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 135(16). doi: 10.4045/tidsskr.15.0882.
• Wyller, Vegard Bruun; Reme, Silje & Mollnes, Tom Eirik (2015). Kronisk utmattelsessyndrom/myalgisk encefalopati – sykdomsmekanismer, diagnostikk og behandling. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 135(23/24), p. 2172–2175. doi: 10.4045/tidsskr.15.1180.
• Wyller, Vegard Bruun (2015). Elefanten i rommet. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 135(6). doi: 10.4045/tidsskr.15.0343.
• Wyller, Vegard Bruun Bratholm (2013). Når kronisk syke barn blir voksne. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 133(3). doi: 10.4045/tidsskr.13.0026.
• Winger, Anette; Ekstedt, Mirjam; Wyller, Vegard Bruun & Helseth, Sølvi (2013). "Sometimes it Feels as if The World Goes on Without Me" Adolescents experiences of living with chronic fatigue syndrome.
• Njølstad, Berit Widerøe; Sveen, Unni & Wyller, Vegard Bruun (2012). Gradert aktivitetstilpasning hos ungdom med kronisk utmattelsessyndrom - nyttig eller unyttig? Ergoterapeuten. ISSN 0800-3475. 55(3), p. 25–30.
• Sinnes, Tommy; Melinder, Annika Maria D; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette & Wessel, Ellen Sofie [Show all 8 contributors for this article] (2012). Emotional Stroop and CFS: An fMRI Study.
• Winger, Anette; Wyller, Vegard Bruun; Ekstedt, Mirijam & Helseth, Sølvi (2011). Pain and quality of life among adolescents with chronic fatigue syndrome.
• Vogt, Henrik; Getz, Linn; Ulvestad, Elling & Wyller, Vegard Bruun (2011). Det udelte mennesket. Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116.

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