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Neuropsychological Performance in Persons With Chronic Fatigue Syndrome: Results From a Population-Based Study

Majer, Matthias PhD; Welberg, Leonie A. M. PhD; Capuron, Lucile PhD; Miller, Andrew H. MD; Pagnoni, Giuseppe PhD; Reeves, William C. MD, MSc

doi: 10.1097/PSY.0b013e31817b9793
Original Articles

Objective: To examine the neuropsychological function characterized in subjects with chronic fatigue syndrome (CFS) at the same time controlling for relevant confounding factors. CFS is associated with symptoms of neuropsychological dysfunction. Objective measures of neuropsychological performance have yielded inconsistent results possibly due to sample selection bias, diagnostic heterogeneity, comorbid psychiatric disorders, and medication usage.

Method: CFS subjects (n = 58) and well controls (n = 104) from a population-based sample were evaluated, using standardized symptom severity criteria. Subjects who had major psychiatric disorders or took medications known to influence cognition were excluded. Neuropsychological function was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results: Compared with controls, CFS subjects exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task. CFS subjects also exhibited alterations in working memory as manifested by a less efficient search strategy on the spatial working memory task, fewer % correct responses on the spatial recognition task, and prolonged latency to a correct response on the pattern recognition task. A significantly higher percentage of CFS subjects versus controls exhibited evidence of neuropsychological impairment (defined by performance 1 standard deviation below the CANTAB normative mean) in tasks of motor speed and spatial working memory. Impairment in CFS subjects versus control subjects ranged from 20% versus 4.8% in five-choice movement time (p = .002) to 27.8% versus 10.6% in search strategy on the spatial working memory task (p = .006).

Conclusions: These results confirm and quantify alterations in motor speed and working memory in CFS subjects independent of comorbid psychiatric disease and medication usage.

CFS = chronic fatigue syndrome; MFI = Multidimensional Fatigue Inventory; SCID = Structured Clinical Interview for DSM-IV; SDS = Zung Self-Rating Depression Scale; WRAT-3 = Wide Range Achievement Test 3; CANTAB = Cambridge Neuropsychological Test Automated Battery; RTI = reaction time; RVIP = rapid visual information processing; SWM = spatial working memory; PRM = pattern recognition memory; SRM = spatial recognition memory; EDS = extra-dimensional shift; ANCOVA = analysis of covariance; MANCOVA = multivariate analysis of covariance.

From the Department of Psychiatry and Behavioral Sciences (M.M., L.A.M.W., L.C., A.H.M., G.P.), Emory University School of Medicine, Atlanta, Georgia; 2Chronic Viral Diseases Branch (W.C.R.), Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

Address correspondence and reprint requests to William C. Reeves, Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop A15, Atlanta, GA 30333. E-mail:

Received for publication May 22, 2007; revision received February 28, 2008.

The study was fully funded by the US Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.

Copyright © 2008 by American Psychosomatic Society
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