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      Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction

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          Abstract

          Objectives

          To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction.

          Methods

          Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV).

          Results

          Cognitive performance in unselected CFS patients is in average range on most measures. However, 0–23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition.

          Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050).

          Conclusion

          Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed.

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          Most cited references24

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          Pattern span: a tool for unwelding visuo-spatial memory.

          Evidence showing that non-verbal short-term memory has distinct visual and spatial/sequential components is reviewed. A new test, The Visual Patterns Test (VPT), which was designed to measure short-term visual memory largely shorn of its spatio-sequential component, is described. Correlational studies of the VPT and the Corsi Blocks Test with healthy subjects and brain-damaged patients indicate a separation between visual and sequential abilities. This separation of function is supported by double dissociations shown by patients. Moreover, in a selective interference experiment, the VPT and the Corsi tests were found to show a double dissociation pattern of interference from visual and spatio sequential subsidiary tasks, respectively. The present results are discussed in relation to other findings in the literature, and it is concluded that non-verbal short-term memory can indeed be viewed as comprising distinct visual and spatio-sequential components. The VPT will be a useful neuropsychological instrument for measuring the visual component.
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            Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review.

            The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects.
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              Symptoms of autonomic dysfunction in chronic fatigue syndrome.

              Chronic fatigue syndrome (CFS) is common and its cause is unknown. To study the prevalence of autonomic dysfunction in CFS, and to develop diagnostic criteria. Cross-sectional study with independent derivation and validation phases. Symptoms of autonomic dysfunction were assessed using the Composite Autonomic Symptom Scale (COMPASS). Fatigue was assessed using the Fatigue Impact Scale (FIS). Subjects were studied in two groups: phase 1 (derivation phase), 40 CFS patients and 40 age- and sex-matched controls; phase 2 (validation phase), 30 CFS patients, 37 normal controls and 60 patients with primary biliary cirrhosis. Symptoms of autonomic dysfunction were strongly and reproducibly associated with the presence of CFS or primary biliary cirrhosis (PBC), and correlated with severity of fatigue. Total COMPASS score >32.5 was identified in phase 1 as a diagnostic criterion for autonomic dysfunction in CFS patients, and was shown in phase 2 to have a positive predictive value of 0.96 (95%CI 0.86-0.99) and a negative predictive value of 0.84 (0.70-0.93) for the diagnosis of CFS. Autonomic dysfunction is strongly associated with fatigue in some, but not all, CFS and PBC patients. We postulate the existence of a 'cross-cutting' aetiological process of dysautonomia-associated fatigue (DAF). COMPASS >32.5 is a valid diagnostic criterion for autonomic dysfunction in CFS and PBC, and can be used to identify patients for targeted intervention studies.
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                Author and article information

                Contributors
                Role: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 February 2019
                2019
                : 14
                : 2
                : e0210394
                Affiliations
                [1 ] School of Psychology, Newcastle University, Newcastle, United Kingdom, and Northumbria Healthcare NHS Foundation Trust, Newcastle, United Kingdom
                [2 ] Institute of Neuroscience, Newcastle University, The Henry Wellcome Building, Framlington Place, Newcastle upon Tyne, United Kingdom
                [3 ] Academic Psychiatry and Regional Affective Disorders Service Newcastle University, Newcastle upon Tyne, United Kingdom, and Northumberland, Tyne and Wear Foundation Trust, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom
                [4 ] Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom
                [5 ] Newcastle Hospitals NHS Foundation Trust, Newcastle, United Kingdom
                Texas Technical University Health Sciences Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-2558-3367
                http://orcid.org/0000-0002-1249-5253
                Article
                PONE-D-18-17107
                10.1371/journal.pone.0210394
                6363139
                30721241
                256ba370-a43b-474c-acba-43cdd22ae21b
                © 2019 Robinson et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 June 2018
                : 21 December 2018
                Page count
                Figures: 0, Tables: 2, Pages: 12
                Funding
                Funded by: Medical Research Council UK
                Award Recipient :
                This research was funded by the Medical research Council, UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
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                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
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                Medicine and Health Sciences
                Neurology
                Neuromuscular Diseases
                Chronic Fatigue Syndrome
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