Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.
Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity).



We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls.



The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups.



CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS.
Expert Centre for Chronic Fatigue, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen. Electronic address: marieke.vandershcaaf@donders.ru.nl.
Marieke E
ME
van der Schaaf
Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen.
Floris P
FP
De Lange
Expert Centre for Chronic Fatigue, Nijmegen.
Iris C
IC
Schmits
Department of Psychiatry, Radboud University Medical Center, Nijmegen; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroimaging, Radboud University Nijmegen, Nijmegen; Adult Personality Disorder Service, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
Dirk E M
DEM
Geurts
Expert Centre for Chronic Fatigue, Nijmegen.
Karin
K
Roelofs
Department of Internal Medicine, Nijmegen.
Jos W M
JWM
van der Meer
Expert Centre for Chronic Fatigue, Nijmegen.
Ivan
I
Toni
Expert Centre for Chronic Fatigue, Nijmegen; Department of Medical Psychology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Hans
H
Knoop
D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D010146:Pain / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult
D005971:Glutamates; D001224:Aspartic Acid; C000179:N-acetylaspartate; C016195:N-acetylglutamic acid; D003401:Creatine
Chronic fatigue syndrome; Dorsolateral prefrontal cortex; Gray matter volume; Magnetic resonance spectroscopy; N-acetylaspartate; Voxel-based morphometry