Publications
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Kongsnes, Berit Elise Bergem; Asprusten, Tarjei Tørre; Wyller, Vegard Bruun Bratholm & Pedersen, Maria
(2026).
The association between hair cortisol levels, Epstein-Barr virus infections and chronic fatigue in adolescents.
Stress.
ISSN 1025-3890.
29(1).
doi:
10.1080/10253890.2026.2638303.
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Brodwall, Elias Myrstad; Selvakumar, Joel Pradeepkumar; Havdal, Lise Beier; Sommen, Silke Lauren; Lund-Berven, Lise & Cvejic, Erin
[Show all 8 contributors for this article]
(2025).
Predictors of fatigue progression in long COVID among young people.
Brain, Behavior, and Immunity - Health (BBI - Health).
45.
doi:
10.1016/j.bbih.2025.100982.
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Long COVID, or post-COVID-19 condition (PCC), has emerged as a significant health concern, with fatigue being the most prevalent persistent symptom among young people. However, research on predictors of fatigue progression in young populations is limited. This study aimed to investigate factors during acute SARS-CoV-2 infection that could predict fatigue progression between six and 12 months post-infection in a cohort of young people with chronic fatigue following COVID-19. Data from the Long-Term Effects of COVID-19 in Adolescents (LoTECA) project were analyzed. A total of 93 participants (mean age 18.5 years, 84 % female) with chronic fatigue at six months, completed the 12-month follow-up. Multivariate analyses identified non-European ethnicity, higher interferon gamma (IFN-γ) levels, and lower RR-interval (higher resting heart rate) during acute infection as significant predictors of fatigue progression from six to 12 months. These three factors explained 21 % of the variance in the fatigue score, highlighting the importance of ethnicity, immune response, and autonomic function in the trajectory of long COVID fatigue. Early identification and targeted interventions, particularly for ethnic minorities and those with specific immune or autonomic markers during acute infection, may be helpful in reducing long-term fatigue. Further research is needed to explore treatment strategies for affected young populations.
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Nerli, Tom Farmen; Selvakumar, Joel Pradeepkumar; Cvejic, Erin; Heier, Ingar; Pedersen, Maria & Johnsen, Tone Langjordet
[Show all 7 contributors for this article]
(2024).
Brief Outpatient Rehabilitation Program for Post-COVID-19 Condition: A Randomized Clinical Trial.
JAMA Network Open.
7(12),
p. 1–16.
doi:
10.1001/jamanetworkopen.2024.50744.
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Importance Post–COVID-19 condition (PCC) is emerging as a common and debilitating condition with few treatment options. Objective To assess the effectiveness of a brief outpatient rehabilitation program based on a cognitive and behavioral approach for patients with PCC. Design, Setting, and Participants Patients with mild to moderate PCC were randomized 1:1 to an established transdiagnostic rehabilitation program or care as usual at a single referral center recruiting from the region of the South-Eastern Norway Regional Health Authority. Participants were followed up after treatment completion and 12 months after enrollment using participant-reported outcome measures. Data were collected from February 22, 2022, until April 15, 2024. Intention-to-treat analysis was performed. Intervention The program consisted of 2 to 8 outpatient encounters with approximately 2 to 6 weeks between each encounter. The intervention was theoretically grounded in the cognitive activation theory of stress, and physicians and physiotherapists were trained in cognitive and behavioral approaches with targeted negative stimuli and response outcome expectancies being particularly important. Main Outcomes and Measures Participant-reported physical function assessed by the Short-Form Health Survey 36 Physical Function Subscale (SF-36-PFS) served as the primary outcome. Secondary outcome measures were the remaining subscales of the SF-36, return to work self-efficacy and symptom scores on fatigue, postexertional malaise, breathlessness, cognitive difficulties, sleep problems, anxiety and depression symptoms, and smell and taste abnormalities. Safety measures included primary health care contacts; hospital admissions; initiation of pharmacologic and/or nonpharmacologic therapy; occurrence of novel disease, illness, or other health problems; worsening of selected key symptoms; working abilities; and thoughts of suicide. Results A total of 473 patients with mild to moderate PCC were assessed for eligibility (n = 364 physician referred; n = 109 self-referred); 314 were included (225 females [72%]; mean [SD] age, 43 [12] years) and 231 completed the primary end point evaluation. The SF-36-PFS scores improved statistically and clinically significantly in the intervention group (score difference between groups, 9.2; 95% CI, 4.3-14.2; P < .001; Cohen d = 0.43; intention-to-treat analysis). The effect was sustained over time. Most secondary and safety measures favored the intervention. Conclusions and Relevance In this randomized clinical trial, a brief outpatient rehabilitation program with a cognitive and behavioral approach in patients with PCC was effective and safe. This trial adds to the evidence supporting such interventions in routine clinical care. Future research should investigate which elements of this approach are the most effective and identify subgroups for which the current treatment is most relevant. Trial Registration ClinicalTrials.gov Identifier: NCT05196451
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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.
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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.
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Øie, Merete Glenne; Buer, Sofie; Bølgen, Maria Sletten; 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.
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Objective Cognitive difficulties are among the most disruptive and disabling problems reported by chronic fatigue syndrome (CFS) sufferers. Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and CFS. The aim of this study was to investigate subjectively reported and objectively measured cognitive functioning in fatigued and non-fatigued adolescents six months after EBV infection. Methods A total of 195 adolescents (12–19 years) with acute EBV infection were followed prospectively for six months, after which they were grouped as chronically fatigued (CF+) and non-fatigued (CF−) cases based on questionnaire score; the CF+-group was further subgrouped according to CFS diagnosis. A group of 70 healthy controls was also included. Groups were cross-sectionally compared on objective measures of processing speed, executive functions and memory, and subjective cognitive functioning. Results There were no group differences regarding objective cognitive measures, but the CF+-group reported significantly (p < 0.001) more cognitive problems (cognitive symptoms sum score = 9.5) compared to the CF−-group (cognitive symptoms sum score = 5.3) and the healthy control group (cognitive symptoms sum score = 6.4). The CFS subgroup rated symptoms scores even higher but did not differ on cognitive performance tests. Conclusion Subjective experiences of cognitive difficulties characterize adolescents with CF and CFS six months after acute EBV infection, whereas objective measures of cognitive impairment are inconspicuous.
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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.
12.
doi:
10.3389/fimmu.2021.715102.
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Background: Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics. Methods: Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated in vitro (n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91, in vitro and plasma cohorts, respectively. Results: Broad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased β-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group. Conclusion: Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.
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Malik, Sadaf; Asprusten, Tarjei Tørre; Pedersen, Maria; Mangersnes, Julie; Trondalen, Gro & Roy, Betty Van
[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.
4:e000797,
p. 1–10.
doi:
10.1136/bmjpo-2020-000797.
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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
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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.
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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.
3(1).
doi:
10.1136/bmjpo-2018-000390.
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We assessed referring medical practitioner’s ability to predict chronic fatigue development in adolescents presenting with acute infectious mononucleosis. Compared with ‘not fatigued’ being predicted as ‘unsurely fatigued’ and ‘likely fatigued’ were both strongly associated with developing fatigue 6 months later (OR 2.5, 95% CI 1.16% to 5.47% and 3.2, 95% CI 1.19% to 8.61%, respectively, P=0.012). The positive and negative predictive values were 66% and 62%, respectively. Disentangling the physician’s intuition may be of interest in further investigations of risk factors and prophylactic factors for fatigue development.
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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.
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Aim: Acute Epstein-Barr virus (EBV) infection is a trigger of prolonged fatigue. This study investigated baseline predictors of physical activity six months after an acute EBV infection. Methods: A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. In this exploratory study, we performed linear regression analysis to assess possible associations between baseline predictors and steps per day at six months. Results: In the final multiple linear regression model, physical activity six months after acute EBV infection was significantly and independently predicted by baseline physical activity (steps per day), substance use (alcohol and illicit drugs) and human growth hormone (adjusted R2 = 0.20). Conclusion: Baseline physical activity, substance use and plasma growth hormone are independent predictors of physical activity six months after an acute EBV infection in adolescents, whereas markers of the infection and associated immune response do not seem to be associated with physical activity six months later.
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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.
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Introduction Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to explore clinical symptoms as well as markers of disease mechanisms in fatigued and non-fatigued adolescents 6 months after EBV-infection, and in healthy controls. Materials and methods A total of 200 adolescents (12–20 years old) with acute EBV infection were assessed 6 months after the initial infectious event and divided into fatigued (EBV CF+) and non-fatigued (EBV CF−) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of 70 healthy controls with similar distribution of sex and age was included. Symptoms were mapped with a questionnaire. Laboratory assays included EBV PCR and serology; detailed blood leukocyte phenotyping and serum high-sensitive C-reactive protein; and plasma and urine cortisol and catecholamines. Assessment of autonomic activity was performed with continuous, non-invasive monitoring of cardiovascular variables during supine rest, controlled breathing and upright standing. Differences between EBV CF+ and EBV CF− were assessed by simple and multiple linear regression adjusting for sex as well as symptoms of depression and anxiety. A p-value ≤ 0.05 was considered statistically significant. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). Results The EBV CF+ group had significantly higher scores for all clinical symptoms. All markers of infection and most immune, neuroendocrine and autonomic markers were similar across the EBV CF+ and EBV CF− group. However, the EBV CF+ group had slightly higher serum C-reactive protein (0.48 vs 0.43 mg/L, p = 0.031, high-sensitive assay), total T cell (CD3+) count (median 1573 vs 1481 × 106 cells/L, p = 0.012), plasma norepinephrine (1420 vs 1113 pmol/L, p = 0.01) and plasma epinephrine (363 vs 237 nmol/L, p = 0.032); lower low-frequency:high frequency (LF/HF) ratio of heart rate variability at supine rest (0.63 vs 0.76, p = 0.008); and an attenuated decline in LF/HF ratio during controlled breathing (−0.11 vs −0.25, p = 0.002). Subgrouping according to different CFS diagnostic criteria did not significantly alter the results. Within the EBV CF+ group, there were no strong correlations between clinical symptoms and markers of disease mechanisms. In a multiple regression analysis, serum CRP levels were independently associated with serum cortisol (B = 4.5 × 10−4, p < 0.001), urine norepinephrine (B = 9.6 × 10−2, p = 0.044) and high-frequency power of heart rate variability (B = –3.7 × 10−2, p = 0.024). Conclusions In adolescents, CF and CFS 6 months after acute EBV infection are associated with high symptom burden, but no signs of increased viral load and only subtle alterations of immune, autonomic, and neuroendocrine markers of which no one is strongly correlated with symptom scores. A slight sympathetic over parasympathetic predominance is evident in CF and might explain slightly increased CRP levels.
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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.
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Introduction Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. Materials and methods A total of 200 adolescents (12–20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). Results In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09–1.6]), pain severity (0.2[0.02–0.3]), functional impairment (1000 steps/day) (−0.3[−0.5 to −0.08]), negative emotions (anxiety) (0.4[0.2–0.6]), verbal memory (correct word recognition) (1.7[0.1–3.3]), plasma C-reactive protein (2.8[1.1–4.4] for CRP values >0.86) and plasma Vitamin B12 (−0.005[−0.01 to −0.001]). Conclusions Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes.
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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.
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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.
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Reme, Silje Endresen; Landmark, Live; Asprusten, Tarjei Tørre; Suvatne, Christer; Herner, Linn Breen & Drivenes, Elin
[Show all 63 contributors for this article]
(2026).
Gi pasientene livet tilbake.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
146.
doi:
10.4045/tidsskr.26.0480.
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Vi vet nok til å kunne hjelpe langt flere pasienter med langvarige symptomer. Likevel holder vi tilbake håpet, av frykt for å skuffe. Det kan koste pasientene store deler av livet.
Denne kronikken er et faglig opprop fra 63 klinikere, forskere og fagpersoner fra hele landet. Vi har klinisk og forskningsmessig erfaring med vedvarende fysiske symptomer, som smerter, utmattelse, «hjernetåke», svimmelhet og mageplager og har samlet oss om et felles budskap: Ny kunnskap om hvordan slike symptomer oppstår og opprettholdes gir grunn til langt større håp om bedring enn mange pasienter får formidlet i dag.
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Boye, Birgitte; Abrahamsen, Cathrine; Helgeland, Helene; Kristiansen, Hege; Diseth, Trond Haaken & Elgen, Irene Bircow
[Show all 8 contributors for this article]
(2026).
Jan Christian Vestre, Helse Midt-Norge | Jan Christian Vestre: Leger krever krafttak mot funksjonelle lidelser.
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Én av tre pasienter ved norske sykehus lider av plager leger ikke finner ut av. Samfunnskostnadene er enorme.
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Published
Nov. 3, 2022 1:55 PM
- Last modified
Apr. 12, 2023 3:04 PM
