Fatigue and inflammation
: A psychoneuroimmunological approach o chronic fatigue

Student thesis: Doctoral ThesisDoctor of Philosophy


Chronic Fatigue Syndrome (CFS) is characterised by severe fatigue, endured
for at least six months, together with symptoms including impaired cognitive
function, sleep disturbance, and musculoskeletal pain. The pathogenesis is still
unknown, resulting in a lack of treatment options and the stigmatization of
patients. Both psychological and biological factors have been implicated in the
development of CFS. To date, evidence has come largely from cross-sectional
studies, and there have been a paucity of longitudinal studies.
The aim of this study was to explore interferon-alpha (IFN-α) induced persistent
fatigue as a proxy model of CFS. IFN-α is an immunotherapy for chronic
Hepatitis C Virus (HCV) infection. It induces a range of side effects including
fatigue, which in some patients persists post-treatment. This model allows for
the identification of risk factors and monitoring of biological and behavioural
changes from the perspective of the trigger, to determine factors relevant to the
persistence of fatigue after the original stimulus is no longer present. Fifty-five
patients undergoing IFN-α treatment for chronic HCV were assessed at
baseline, during treatment, and six-months post-treatment. Clinical,
inflammatory and cortisol measures were obtained. Fifty-four CFS patients and
57 healthy volunteers completed the same measures at a one-off assessment,
which were compared with post-treatment measures from HCV persistent and
resolved fatigue patients.
IFN-α induced persistent fatigue was associated with an exaggerated response
to IFN-α, with increased fatigue, depressive symptoms, and perceived stress, a
greater decline in health status, and higher inflammation. This higher
symptomatology during treatment put these patients at a disadvantage for their
subsequent recovery. Neither IFN-α induced persistent fatigue nor CFS was
associated with continued peripheral inflammation, emphasising the importance
of the response to the initial trigger. Future studies are needed to elucidate the
mechanisms behind the exaggerated response, and the ‘conversion’ to chronic
illness in the absence of peripheral immune activation.
Date of Award2017
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorCarmine Pariante (Supervisor) & Patricia Zunszain (Supervisor)

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