Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls

Abstract:

OBJECT: Chronic fatigue syndrome (CFS) patients report usually cognitive complaints. They also have frequently comorbid depression that can be considered a possible explanation for their cognitive dysfunction. We evaluated the cognitive performance of patients with CFS in comparison with a control group of healthy volunteers and a group of patients with MDD.

PATIENTS AND METHODS: Twenty-five patients with CFS, 25 patients with major depressive disorder (MDD), and 25 healthy control subjects were given standardized tests of attention, working memory, and verbal and visual episodic memory, and were also tested for effects related to lack of effort/simulation, suggestibility, and fatigue.

RESULTS: Patients with CFS had slower phasic alertness, and also had impaired working, visual and verbal episodic memory compared to controls. They were, however, no more sensitive than the other groups to suggestibility or to fatigue induced during the cognitive session. Cognitive impairments in MDD patients were strongly associated with depression and subjective fatigue; in patients with CFS, there was a weaker correlation between cognition and depression (and no correlation with fatigue).

CONCLUSIONS: This study confirms the presence of an objective impairment in attention and memory in patients with CFS but with good mobilization of effort and without exaggerated suggestibility.

Copyright © 2011 Elsevier B.V. All rights reserved.

 

Source: Constant EL, Adam S, Gillain B, Lambert M, Masquelier E, Seron X. Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls. Clin Neurol Neurosurg. 2011 May;113(4):295-302. doi: 10.1016/j.clineuro.2010.12.002. Epub 2011 Jan 20. https://www.ncbi.nlm.nih.gov/pubmed/21255911

 

The role of depression in cognitive impairment in patients with chronic fatigue syndrome

Abstract:

BACKGROUND AND OBJECTIVE: To analyze the role of depression in cognitive deficits of patients with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: 57 women with CFS were assessed by neuropsychological tests that included measures of attention: CalCap, Mental control of the WMS-III, PASAT, forward and backward digits (WAIS-III), symbol digit modalities test (SDMT); executive functions: Stroop Test, Trail Making Test (TMT A y B), FAS, Tower of London; memory: Auditory-Verbal Learning Test (AVL), Rey Complex Figure (RCF), and psychomotor skills: Grooved Pegboard. The raw scores on the tests were adjusted according to normative data and transformed to T scores. The sample was divided into two groups based on the presence or absence of depression, assessed by clinical interview and administration of the Hospital Anxiety and Depression Scale (HADS). This study compared neuropsychological test scores between the two groups.

RESULTS: CFS patients showed cognitive deficit in attention and executive functions, regardless of the presence of depression. There were no significant differences between the two CFS groups.

CONCLUSIONS: The cognitive impairments in patients with CFS are not secondary to the presence of depression. These results should be taken into account in the implementation of therapeutic programs in these patients.

Copyright © 2010 Elsevier España, S.L. All rights reserved.

 

Source: Santamarina-Pérez P, Freniche V, Eiroa-Orosa FJ, Llobet G, Sáez N, Alegre J, Jacas C. The role of depression in cognitive impairment in patients with chronic fatigue syndrome. Med Clin (Barc). 2011 Mar 12;136(6):239-43. doi: 10.1016/j.medcli.2010.07.022. Epub 2010 Dec 9. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21145567

 

Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder

Abstract:

Chronic fatigue syndrome (CFS), a complex illness characterized by fatigue, impaired concentration, and musculoskeletal pain, is often misdiagnosed as a psychiatric illness due to the overlap of its symptoms with mood and anxiety disorders. Using proton magnetic resonance spectroscopic imaging ((1)H MRSI), we previously measured levels of the major brain metabolites in CFS, in generalized anxiety disorder (GAD), and in healthy control subjects, and found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in CFS compared to the other two groups.

In the present study, we sought to assess the specificity of this observation for CFS by comparing ventricular lactate levels in a new cohort of 17 CFS subjects with those in 19 healthy volunteers and in 21 subjects with major depressive disorder (MDD), which, like GAD, is a neuropsychiatric disorder that has significant symptom overlap with CFS.

Ventricular CSF lactate was significantly elevated in CFS compared to healthy volunteers, replicating the major result of our previous study. Ventricular lactate measures in MDD did not differ from those in either CFS or healthy volunteers. We found a significant correlation between ventricular CSF lactate and severity of mental fatigue that was specific to the CFS group.

In an exploratory analysis, we did not find evidence for altered levels of the amino acid neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate + glutamine (‘Glx’), in CFS compared to MDD or healthy controls. Future (1)H MRS studies with larger sample sizes and well-characterized populations will be necessary to further clarify the sensitivity and specificity of neurometabolic abnormalities in CFS and MDD.

 

Source: Murrough JW, Mao X, Collins KA, Kelly C, Andrade G, Nestadt P, Levine SM, Mathew SJ, Shungu DC. Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR Biomed. 2010 Jul;23(6):643-50. doi: 10.1002/nbm.1512. https://www.ncbi.nlm.nih.gov/pubmed/20661876

 

Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction

Abstract:

OBJECTIVES: To evaluate electromyogram (EMG) profiles in patients with three related conditions: fibromyalgia, chronic fatigue syndrome, and depression.

METHODS: We studied 44 healthy volunteers, 22 patients with fibromyalgia, 11 patients with chronic fatigue syndrome, and 10 patients admitted for depression. The trapezius electromyogram was recorded during maximally sustained, bilateral, 90 degrees abduction of the shoulders. EMG signal frequency and amplitude were measured throughout the test.

RESULTS: In the fibromyalgia group, isometric contraction duration was significantly shorter than in the other two patient groups (P<0.001) and the EMG frequency and amplitude pattern indicated premature discontinuation of the muscle contraction. Findings in the chronic fatigue patients were similar to those in the healthy controls. The patients with depression had a distinctive EMG profile characterized by excessive initial motor-unit recruitment with a shift in the frequency spectrum.

CONCLUSIONS: Fibromyalgia was associated with a specific EMG pattern indicating premature discontinuation of the muscle contraction. Therefore, maximal voluntary muscle contraction tests may be of limited value for assessing function in fibromyalgia patients. Chronic fatigue syndrome patients had similar EMG findings to those in the healthy controls. The EMG alterations in the patients with depression were consistent with manifestations of psychomotor retardation.

Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

 

Source: Maquet D, Croisier JL, Dupont C, Moutschen M, Ansseau M, Zeevaert B, Crielaard JM. Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction. Joint Bone Spine. 2010 May;77(3):264-7. doi: 10.1016/j.jbspin.2010.02.003. Epub 2010 Apr 22. https://www.ncbi.nlm.nih.gov/pubmed/20417143

 

Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis / chronic fatigue syndrome

Abstract:

BACKGROUND: There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue syndrome(ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e. activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways.

OBJECTIVE: The aim of the present study was to examine the urinary excretion of 8-hydroxy-deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS.

METHODS: Toward this end, morning urine was sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25 with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale.

RESULTS: We found that 49.0% of the variance in the urinary excretion of 8-OHdG was predicted by the regression on creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the residualized 8-OHdG values after partialling out the effects of creatinine and not by computing the 8-OHdG / creatinine ratio. We found that the residualized urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in patients with depression and ME/CFS than in normal controls and all other patients. In the patient group, there were significant correlations between the urinary 8-OHdG and the total score on the FF scale and sadness and flu-like malaise.

CONCLUSIONS: The findings show increased oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore, further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and neurodegenerative processes in depression.

 

Source: Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis / chronic fatigue syndrome. Neuro Endocrinol Lett. 2009;30(6):715-22. https://www.ncbi.nlm.nih.gov/pubmed/20035260

 

Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study

Abstract:

BACKGROUND: Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder (MDD) reported similarities as well as differences between the two disorders. However, whereas psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited. Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded inconsistent results. This study hence directly compares fine psychomotor functioning in both syndromes.

METHODS: Thirty-eight patients diagnosed with CFS without a current major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two computerized copying tasks differing in complexity: a line-copying task that mainly requires motor effort and a figure-copying task requiring additional cognitive efforts. All participants were female. A multivariate general linear model was used to compute group differences.

RESULT: Overall, both patient groups performed more slowly than the controls. Compared to CFS patients, patients with MDD needed significantly more time to copy the single lines but no such between-group performance difference was observed for the figure reproductions. In this latter copying task, the increasing complexity of the figures resulted in prolonged reaction times for all three participant groups with the effect being larger and the magnitude similar for the two patient groups.

LIMITATIONS: All patients were female and most were on psychotropic medication.

CONCLUSIONS: Both the MDD and CFS patients tested demonstrated an overall fine motor slowing, with the motor component being more affected in the MDD patients than in the CFS patients while both patient groups showed similar cognitive impairments.

 

Source: Schrijvers D, Van Den Eede F, Maas Y, Cosyns P, Hulstijn W, Sabbe BG. Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study. J Affect Disord. 2009 May;115(1-2):46-53. doi: 10.1016/j.jad.2008.08.010. Epub 2008 Sep 24. https://www.ncbi.nlm.nih.gov/pubmed/18817977

 

An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS

Abstract:

BACKGROUND: It has been shown that chronic fatigue syndrome (CFS) and major depression (MDD) are accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS and MDD are accompanied by an IgM-mediated immune response directed against nitro-serum bovine albumin (BSA), which is a neoepitope of BSA formed by damage caused by nitrosative stress.

AIMS: Toward this end, we examined serum IgM antibodies to nitro-BSA in 13 patients with CFS, 14 subjects with partial CFS, 16 patients with MDD and 11 normal controls.

RESULTS: We found that the prevalence and mean values for the serum IgM levels directed against nitro-BSA were significantly greater in patients with partial CFS, CFS and MDD than in normal controls, and significantly greater in CFS than in those with partial CFS and MDD. We found significant and positive correlations between serum IgM levels directed against nitro-BSA and symptoms of the FibroFatigue scale, i.e. aches and pain and muscular tension. There was also a strong positive correlation between serum IgM titers directed against nitro-BSA and an index of increased gut permeability (“leaky gut”), i.e. serum IgM and IgA directed against LPS of different gram-negative enterobacteria.

DISCUSSION: The above mentioned results indicate that both CFS and MDD are accompanied by a) an increased gut permeability which has allowed an exaggerated passage of BSA through a compromised epithelial barrier; b) increased nitrosative stress which has induced damage to BSA; and c) an IgM-mediated immune response which is directed against the nitro-BSA neoepitopes. Nitrosative stress is one of the factors underpinning the comorbidity and clinical overlap between CFS and MDD.

 

Source: Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9. https://www.ncbi.nlm.nih.gov/pubmed/18580855

 

A systematic review of chronic fatigue syndrome: don’t assume it’s depression

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is characterized by profound, debilitating fatigue and a combination of several other symptoms resulting in substantial reduction in occupational, personal, social, and educational status. CFS is often misdiagnosed as depression. The objective of this study was to evaluate and discuss different etiologies, approaches, and management strategies of CFS and to present ways to differentiate it from the fatigue symptom of depression.

DATA SOURCES: A MEDLINE search was conducted to identify existing information about CFS and depression using the headings chronic fatigue syndrome AND depression. The alternative terms major depressive disorder and mood disorder were also searched in conjunction with the term chronic fatigue syndrome. Additionally, MEDLINE was searched using the term chronic fatigue. All searches were limited to articles published within the last 10 years, in English. A total of 302 articles were identified by these searches. Also, the term chronic fatigue syndrome was searched by itself. This search was limited to articles published within the last 5 years, in English, and resulted in an additional 460 articles. Additional publications were identified by manually searching the reference lists of the articles from both searches.

STUDY SELECTION AND DATA EXTRACTION: CFS definitions, etiologies, differential diagnoses (especially depression) and management strategies were extracted, reviewed, and summarized to meet the objectives of this article.

DATA SYNTHESIS: CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression. Genetic, immunologic, infectious, metabolic, and neurologic etiologies were suggested to explain CFS. A biopsychosocial model was suggested for evaluating, managing, and differentiating CFS from depression.

CONCLUSIONS: Evaluating and managing chronic fatigue is a challenging situation for physicians, as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.

 

Source: Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: don’t assume it’s depression. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/ (Full article)

 

Differential diagnosis of chronic fatigue syndrome and major depressive disorder

Abstract:

The goal of this study was to identify variables that successfully differentiated patients with chronic fatigue syndrome, major depressive disorder, and controls. Fifteen participants were recruited for each of these three groups, and discriminant function analyses were conducted.

Using symptom occurrence and severity data from the Fukuda et al. (1994) definitional criteria, the best predictors were postexertional malaise, unrefreshing sleep, and impaired memory-concentration. Symptom occurrence variables only correctly classified 84.4% of cases, whereas 91.1% were correctly classified when using symptom severity ratings. Finally, when using percentage of time fatigue reported, postexertional malaise severity, unrefreshing sleep severity, confusion-disorientation severity, shortness of breath severity, and self-reproach to predict group membership, 100% were classified correctly.

 

Source: Hawk C, Jason LA, Torres-Harding S. Differential diagnosis of chronic fatigue syndrome and major depressive disorder. Int J Behav Med. 2006;13(3):244-51. https://www.ncbi.nlm.nih.gov/pubmed/17078775

 

Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease which defined as medically unexplained, disabling fatigue of 6 months or more duration and often accompanied by several of a long list of physical complaints. We aimed to investigate abnormalities of hypothalamic-pituitary-gonadal (HPG) axis hormones and cortisol concentrations in premenopausal women with CFS and find out effects of depression rate on these hormones.

METHODS: We examined follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and cortisol concentrations in 43 premenopausal women (mean age: 32.86 +/- 7.11) with CFS and compared matched 35 healthy controls (mean age: 31.14 +/- 6.19). Patients were divided according to menstrual cycle phases (follicular and luteal) and compared with matched phase controls. Depression rate was assessed by Beck Depression Inventory (BDI), and patients with high BDI scores were compared to patients with low BDI scores.

RESULTS: There were no significant differences in FSH, LH, estradiol and progesterone levels in both of menstrual phases of patients versus controls. Cortisol levels were significantly lower in patients compared to controls. There were no significant differences in all hormone levels in patients with high depression scores versus patients with low depression scores.

CONCLUSION: In spite of high depression rate, low cortisol concentration and normal HPG axis hormones of both menstrual phases are detected in premenopausal women with CFS. There is no differentiation between patients with high and low depression rate in all hormone levels. Depression condition of CFS may be different from classical depression and evaluation of HPG and HPA axis should be performed for understanding of pathophysiology of CFS and planning of treatment.

 

Source: Cevik R, Gur A, Acar S, Nas K, Sarac AJ. Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones. BMC Musculoskelet Disord. 2004 Dec 8;5:47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539265/ (Full article)