The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

 

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559

 

Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses.

METHODS: Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration.

RESULTS: CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs.

CONCLUSIONS: The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms.

 

Source: Arnold MC, Papanicolaou DA, O’Grady JA, Lotsikas A, Dale JK, Straus SE, Grafman J. Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome. Psychol Med. 2002 Aug;32(6):1075-89. http://www.ncbi.nlm.nih.gov/pubmed/12214788

 

A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome

Abstract:

The present study had two objectives: 1) to determine the characteristics that differentiated subjects with multiple chemical sensitivities (MCS), chemical sensitivities (CS), and chronic fatigue syndrome (CFS); and 2) to evaluate the psychiatric and neuropsychological complaints of these groups relative to normal controls.

A cross-sectional comparison was made of the following groups matched for age, sex, and education: 1) patients whose sensitivities to multiple low level chemical exposures began with a defined exposure (MCS; N = 23); 2) patients with sensitivities to multiple chemicals without a clear date of onset (CS; N = 13); 3) patients meeting CDC criteria for Chronic Fatigue Syndrome (CFS; N = 18); and 4) normal controls (N = 18).

Subjects with sensitivities to chemicals (MCS and CS) reported significantly more lifestyle changes due to chemical sensitivities and significantly more chemical substances that made them ill compared with chronic fatigue and normal controls. MCS, CS, and CFS patients had significantly higher rates of current psychiatric disorders than normal controls and reported significantly more physical symptoms with no medical explanation.

Seventy-four percent of MCS and 61% of CFS did not qualify for any current Axis I psychiatric diagnosis. Chemically sensitive subjects without a defined date of onset (CS) had the highest rate of Axis I psychiatric disorders (69%). On the MMPI-2, 44% of MCS, 42% of CS, 53% of CFS, and none of the controls achieved clinically significant elevations on scales associated with somatoform disorders.

With the exception of one complex test of visual memory, no significant differences were noted among the groups on tests of neuropsychological function. Standardized measures of psychiatric and neuropsychological function did not differentiate subjects with sensitivities to chemicals from those with chronic fatigue. Subjects with sensitivities to chemicals and no clear date of onset had the highest rate of psychiatric morbidity. Standardized neuropsychological tests did not substantiate the cognitive impairment reported symptomatically. Cognitive deficits may become apparent under controlled exposure conditions.

 

Source: Fiedler N, Kipen HM, DeLuca J, Kelly-McNeil K, Natelson B. A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome. Psychosom Med. 1996 Jan-Feb;58(1):38-49. http://www.ncbi.nlm.nih.gov/pubmed/8677287

 

Dimensional assessment of chronic fatigue syndrome

Abstract:

The absence of laboratory tests and clear criteria to identify homogeneous (sub)groups in patients presenting with unexplained fatigue, and to assess clinical status and disability in these patients, calls for further assessment methods. In the present study, a multi-dimensional approach to the assessment of chronic fatigue syndrome (CFS) is evaluated.

Two-hundred and ninety-eight patients with CFS completed a set of postal questionnaires that assessed the behavioural, emotional, social, and cognitive aspects of CFS. By means of statistical analyses nine relatively independent dimensions of CFS were identified along which CFS-assessment and CFS-research can be directed.

These dimensions were named: psychological well-being, functional impairment in daily life, sleep disturbances, avoidance of physical activity, neuropsychological impairment, causal attributions related to the complaints, social functioning, self-efficacy expectations, and subjective experience of the personal situation. A description of the study sample on these dimensions is presented.

 

Source: Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994 Jul;38(5):383-92. http://www.ncbi.nlm.nih.gov/pubmed/7965927

 

Chronic fatigue syndrome in Minnesota

Abstract:

Chronic fatigue syndrome (CFS), an illness characterized by debilitating fatigue and a number of associated symptoms, was identified in 135 patients using the case definition provided in 1988. The demographic features of these patients, 97% of whom resided in Minnesota, were similar to those reported elsewhere.

About three-fourths of the cases occurred between 1984 and 1989, and in 123 (91.1%), the illness began with what appeared to be an acute infection. Patients had been ill for an average of 4.3 years before enrollment in the study.

Fatigue was their most troublesome symptom, although a majority of the patients rated most of the general symptoms and neuropsychological complaints associated with CFS as moderate or severe. Follow-up data obtained on 62 patients one year after initial evaluation revealed that none had completely recovered. However, about 40% reported some improvement in each of the CFS symptoms.

 

Source: Peterson PK, Schenck CH, Sherman R. Chronic fatigue syndrome in Minnesota. Minn Med. 1991 May;74(5):21-6. http://www.ncbi.nlm.nih.gov/pubmed/1861659