Depression and CFIDS

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Depression and CFIDS

I am a librarian, not a medical person - and I needed to turn around the thinking of two psychiatrists who believed that CFS was a form of depression.

To begin with, neither was aware that there was any solid medical literature, a published case definition, or acceptance at any level by the CDC or NIH.

I put together some material (from NIH, CDC, AACFS, and others) and also did a medline search. The search was done only for items in English that also had abstracts. From what was retrieved, I selected about 250 abstracts that I thought were decent and might spark a physician's interest.

From the 250 abstracts, I selected about 30 abstracts that I felt spoke directly to some of the differences between CFS and depression. I then wrote a one page summary, that weaved the references in, and attached the abstracts.

I was not sure of the accuracy of all of my statements in the summary (actually-still am not, and tossed in some material related to Fibromyalgia), but the collection of abstracts did a powerful job of educating and resulted in a turn-around in thinking and an interest in learning more.

Notes compiled by Christyn Billinsky (non-medical person)

Chronic Fatigue Syndrome - a serious chronic illness/condition that impacts many different body systems - brain, central & autonomic nervous system, endocrine system, metabolic system, immune system, GI system, ...

While prolonged fatigue and chronic fatigue are common medical complaints, Chronic Fatigue Syndrome is a very small subset of patients presenting with fatigue. Recent prevalence studies indicate that only 1 or 2 people per 1,000 meet the current CDC case definition for Chronic Fatigue Syndrome.

CFS & DEPRESSION - Though mild to moderate anxiety and depression are common symptoms of the clinical presentation of CFS, roughly 1/3 of people with CFS do not have depression or any other psychiatric illness (NIH, 1996).

Depression is increasingly viewed as another aspect or piece of CFS, not its cause. It is considered to be - 1) part of the disease process (primary biological CNS factors), and 2) a natural reaction to the reality of chronic illness (secondary psychological reaction). When present, it requires aggressive treatment, but within the context of CFS.

CFS depression is frequently treatment resistant. Psychiatrists and other therapists are encouraged to become familiar with CFS as a diagnosis to consider when a depressed patient's mood improves with treatment, but other problems do not. Other problems would include fatigue, lethargy, painful lymph nodes, headaches, muscle pain, joint pain, unrefreshing sleep, cognitive and memory problems, post exertional malaise, inability to do sustained aerobic activity, lightheadedness, dizziness, balance problems, muscle twitching, night sweats, chronic intermittent low grade fevers, ...

Though CFS and depression share some characteristics, the biology behind them appears to differ.

ANTIDEPRESSANT TREATMENT - Most people with CFS cannot tolerate standard therapeutic doses of antidepressants. What frequently works best is lower doses of combinations of antidepressant and antianxiety medications. (Goodnick,1993; Goldenberg,1995,1996; Godfrey,1996)

BRAIN IMAGING STUDIES - While various brain imaging studies have revealed abnormalities that appear to be common to both CFS and depression, differences are also apparent - both in the degree of abnormalities, and the areas of abnormalities. (Schwartz,1994; Mountz,1995; Fischler,1996) A significant area of difference is the brainstem. SPECT scans show hypoperfusion in the brainstem of people with CFS, but not in people with depression (Costa,1995). PET scans show hypometabolism in the brainstem of people with CFS, but not in people with depression (Tavio, AACFS Conf 1996). Brainstem abnormalities are considered to be a likely source of many CFS symptoms.

COGNITIVE PROBLEMS - Cognitive difficulties associated with CFS present different patterns than those associated with depression, and do not resolve with successful treatment of the depressed mood. Impairment in complex information processing speed and efficiency appears to be the source of CFS cognitive difficulties experienced as problems with attention, concentration and memory. Recent studies indicate that this impairment cannot be attributed to affective disorder or other psychopathology. (DeLuca, Schmaling, Marshall, Grafman, AACFS Conf 1996) (DeLuca,1993; Sandman,1993; Smith,1993; Johnson,1994; DeLuca,1995; DeLuca,1997)

EXERCISE - Sustained exercise generally improves depression, but causes serious relapse in CFS. To avoid relapse, a program of extremely low level, carefully graded exercise/activity is recommended for CFS. (McCully,1996; NIH,1996)

NEUROENDOCRINE RESPONSES - Demitrack and others have studied various aspects of contrasting neuroendocrine responses seen in CFS and depression. (Demitrack,1991,1996; Bakheit,1992; Crofford,1994; Gold,1995) " confirm that depression is associated with hypercortisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioral dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders." (Cleare,1995)

SLEEP DISORDER - The sleep disorder in CFS is in non-REM phases, while the sleep disorder in depression is in REM phases. Moldofsky (Moldofsky,1989,1992,1993,1995,1996) has reported extensively on the sleep disorders of CFS, fibromyalgia and depression.


(NIH 1996) Chronic Fatigue Syndrome: Information for Physicians. National Institute of Allergy and Infectious Diseases, National Institutes of Health. NIH Publication No. 96-484. September 1996.

Full text available on the WEB:


(Goodnick 1993) Goodnick PJ, Sandoval R. Psychotropic treatment of Chronic Fatigue Syndrome and related disorders. J CLIN PSYCHIATRY 1993 Jan; 54(1): p13-20.

(Goldenberg 1995) Goldenberg DL, Mayskly M, Mossey C, Ruthazer R, Schmid C. The independent and combined efficacy of fluoxetine and amitriptyline in the treatment of fibromyalgia. ARTHRITIS AND REUMATISM 1995 38(Suppl 9): pS229.

(Goldenberg 1996) Goldenberg DL, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of Fibromyalgia. ARTHRITIS RHEUM 1996 Nov; 39(11): p1852-9.

(Godfrey 1996) Godfrey RG. A guide to the understanding and use of tricyclic antidepressants in the overall management of Fibromyalgia and other chronic pain syndromes. ARCH INTERN MED 1996 May 27; 156(10): p1047-52.


(Schwartz 1994) Schwartz RB, Komaroff AL, Garada BM, Gleit M, Doolittle TH, Bates DW, Vasile RG, Holman BL. SPECT imaging of the brain: comparison of findings in patients with Chronic Fatigue Syndrome, AIDS dementia complex, and major unipolar depression. AJR AM J ROENTGENOL 1994 Apr; 162(4): p943-51.

(Mountz 1995) Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcon GS, Mountz JD. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. ARTHRITIS RHEUM 1995 Jul; 38(7): p926-38.

(Fischler 1996) Fischler B, Dhaenen H, Cluydts R, Michiels V, Demets K, Bossuyt A, Kaufman L, Demeirleir K. Comparison of Tc-99m HMPAO SPECT scan between Chronic Fatigue Syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. NEUROPSYCHOBIOLOGY 1996 34(4): p175-183.

(Costa 1995) Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in Chronic Fatigue Syndrome. QJM 1995 Nov; 88(11): p767-73.

(Tavio, AACFS Conf 1996) Tavio M. Brain Positron Emission Tomography (PET) findings of patients with Chronic Fatigue Syndrome: A Useful Tool for Differential Diagnosis. Presented at the annual meeting of the AACFS, October 1996, San Francisco, CA.

Summary available on the WEB:


(DeLuca, Schmaling, Marshall, Graffman, AACFS Conf 1996) DeLuca J, Schmaling K, Marshall P, Graffman J. Neuropsychological Functioning in CFS. Presented at the annual meeting of the AACFS, October 13, 1996, San Francisco, CA.

Summary available on the WEB:

(DeLuca 1993) DeLuca J, Johnson SK, Natelson BH. Information processing efficiency in Chronic Fatigue Syndrome and Multiple Sclerosis. ARCH NEUROL 1993 Mar; 50(3): p301-4.

(Sandman 1993) Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F. Memory deficits associated with Chronic Fatigue Immune Dysfunction Syndrome. BIOL PSYCHIATRY 1993 Apr 15-May 1; 33(8-9): p618-23.

(Smith 1993) Smith AP, Behan PO, Bell W, Millar K, Bakheit M. Behavioural problems associated with the Chronic Fatigue Syndrome. BR J PSYCHOL 1993 Aug; 84 (Pt 3): p411-23.

(Johnson 1994) Johnson SK, DeLuca J, Fiedler N, Natelson BH. Cognitive functioning of patients with Chronic Fatigue Syndrome. CLIN INFECT DIS 1994 Jan; 18(Suppl 1): pS84-5.

(DeLuca 1995) DeLuca J, Johnson SK, Beldowicz D, Natelson BH. Neuropsychological impairments in Chronic Fatigue Syndrome, Multiple Sclerosis, and depression. J NEUROL NEUROSURG PSYCHIATRY 1995 Jan; 58(1): p38-43.

DeLuca 1997) DeLuca J, Johnson SK, Ellis SP, Natelson BH. Cognitive functioning is impaired in patients with Chronic Fatigue Syndrome devoid of psychiatric disease. J NEUROL NEUROSURG PSYCHIATRY 1997 Feb; 62(2): p151-5.


(McCully 1996) McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of Chronic Fatigue Syndrome. SPORTS MED 1996 Jan; 21(1): p35-48.

(NIH 1996) Chronic Fatigue Syndrome: Information for Physicians. National Institute of Allergy and Infectious Diseases, National Institutes of Health. NIH Publication No. 96-484. September 1996.

Full text available on the WEB:


(Demitrack 1991) Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW. Evidence for impaired activation of the hypothalamic- pituitary-adrenal axis in patients with Chronic Fatigue Syndrome. J CLIN ENDOCRINOL METAB 1991 Dec; 73(6): p1224-34.

(Demitrack 1996) Crofford LJ, Demitrack MA. Evidence that abnormalities of central neurohormonal systems are key to understanding Fibromyalgia and Chronic Fatigue Syndrome RHEUMATIC DISEASE CLINICS OF NORTH AMERICA 1996 May; 22 (2): p267&.

(Bakheit 1992) Bakheit AM, Behan PO, Dinan TG, Gray CE, O'Keane V. Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. BMJ 1992 Apr 18; 304(6833): p1010-2.

(Crofford 1994) Crofford LJ, Pillemer SR, Kalogeras KT, Cash JM, Michelson D, Kling MA, Sternberg EM, Gold PW, Chrousos GP, Wilder RL. Hypothalamic-pituitary- adrenal axis perturbations in patients with Fibromyalgia. ARTHRITIS RHEUM 1994 Nov; 37(11): p1583-92.

(Gold 1995) Gold PW, Licinio J, Wong ML, Chrousos GP. Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. ANN N Y ACAD SCI 1995 Dec 29; 771: p716-29.

(Cleare 1995) Cleare AJ, Bearn J, Allain T, McGregor A, Wessely S, Murray RM, O'Keane V. Contrasting neuroendocrine responses in depression and Chronic Fatigue Syndrome. J AFFECT DISORD 1995 Aug 18; 34(4): p283-9.


(Moldofsky 1989) Moldofsky H. Nonrestorative sleep and symptoms after a febrile illness in patients with fibrositis and Chronic Fatigue Syndromes. J RHEUMATOL SUPPL 1989 Nov; 19: p150-3.

(Moldofsky 1992) Whelton CL, Salit I, Moldofsky H. Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in Chronic Fatigue Syndrome. J RHEUMATOL 1992 Jun; 19(6): p939-43.

(Moldofsky 1993) Moldofsky H. Fibromyalgia, sleep disorder and Chronic Fatigue Syndrome. CIBA FOUND SYMP 1993 173: p262-71; discussion p272-9.

(Moldofsky 1995) Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in Fibromyalgia and Chronic Fatigue Syndrome. ADV NEUROIMMUNOL 1995 5(1): p39- 56.

(Moldofsky 1996) MacFarlane JG, Shahal B, Mously C, Moldofsky H. Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters. SLEEP 1996 Apr; 19(3): p200-4.

© Christyn Billinsky, 1997

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