|
Volume 2, Number 3 |
1st September 1999 |
Vojdani A and Lapp CW. Interferon-induced proteins are elevated in blood samples of patients with chemically or virally induced chronic fatigue syndrome. Immunopharmacology and Immunotoxicology, 1999, 21, 2, 175-202.
Overlapping symptomatologies between CFS and chemical sensitivity have been observed by different investigators. Therefore, it is of great importance to develop biomarker(s) for possible differentiation between viral induced CFS (without sensitivity to chemicals) versus chemically induced CFS. Since interferon induced proteins 2-5A Synthetase and Protein Kinase RNA (PKR) have been implicated in the viral induction of CFS, the objective of this study was to utilise 2-5A and PKR activity for differentiation between CFS induced by either viruses or chemicals.
Twenty patients with CFS (CDC criteria '94) who were positive for viral genome(s) (mainly HHV6; HTLVII, EBV, and CMV) and did not have any history of exposure to toxic chemicals were included in this study. As a comparison, a second group of fatigued patients consisted of twenty individuals from the same geographical area who were negative for viral genomes but had been exposed to methyl tertiary-butyl ether concentrations of up to 70 ppb and benzene concentrations up to 14 ppb (in contaminated drinking water). All the subjects complained of fatigue although some symptoms (exhaustion, malaise, dizziness, and tender glands) were more common among the viral-induced CFS group. From all 40 patients, blood was drawn, leukocyte extract was prepared and assayed for 2-5A Synthetase and PKR activity.
Clinical specimens which were positive for viral genomes showed a 2.2-38.7 fold increase in 2-5A activity and a 1.3-13.5 fold increase in PKR activities over the background of the healthy controls. Similarly, the second group (negative for viral genomes, but exposed to chemicals) showed a 1.1-29.2 fold increase in 2-5A Synthetase and a 1.3-11.6 fold increase in PKR when they were compared to healthy subjects.
To elucidate mechanisms involved in viral versus chemical induction of 2-5A Synthetase and PKR, MDBK (Madin-Darby Bovine Kidney) cell lines were cultured either in the presence or absence of HHV6, MTBE (methyl tertiary-butyl ether), or benzene, heat shock proteins (HSP) and interferon-ß. 2-5A and PKR activities were measured in all the above conditions.
A clear induction of 2-5A and PKR was observed when MDBK cells were exposed to HHV6, MTBE, and benzene. This induction was more significant with heat shock protein (HSP90, HSP70) and IFN-ß indicating their involvement in the mechanism of action. However, when MDBK cells were incubated either with MTBE + benzene or HHV6 in the presence or absence of anti IFN-ß or anti-HSP-70, the activities of both 2-5A and PKR in HHV6 infected cells were inhibited by more than 90% due to addition of anti IFN-ß, and only 20% by addition of anti-HSP70. While in MTBE + benzene exposed cells anti IFN-beta reduced the activity of these enzymes by 40% and anti-HSP70 by more than 90%. This variation in the induction of 2-5A and PKR by anti-HSP70 or IFN-ß indicates involvement of IFN-ß in viral induction 2-5A and PKR, and HSP involvement in chemical induction of these enzymes.
The researchers conclude that 2-5A and PKR are not only biomarkers for viral induction of CFS, but biomarkers to other stressors that include MTBE and benzene.
[Ed. note: In relation to myalgic encephalopathy (ME), it may not be so easy to differentiate between viral and chemically induced onset. The viruses listed are latent in most adults. Moreover, exposure to chemicals has been implicated in some cases of ME. In one epidemic (Franklin, Kentucky 1965), the attack rate was greater in a factory where people had been exposed over two days to mercury added as a fungicide to paint (115/1000), than in those not exposed in the community (5/1000). This suggests that the paint vapour induced symptoms in workers who might otherwise have had a subclinical infection.MTBE and benzene may also be cofactors, suppressing the interferon pathway induced by viral agents.]
Gimenez, HB., Cash, P., Laing, RBS and Douglas, JG. Cytokine expression and morphology of in vitro grown monocytes from patients with chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 47-60.
Blood samples (peripheral blood monocytes) from 25 patients with CFS (CDC criteria '94) and 23 healthy controls were investigated. The samples were fractionated as adherent cells (monocyte-enriched fraction) and non-adherent cells.
It was observed that the morphology (shape and size) of adherent cells from the patients, co-cultivated with homologous non-adherent cells, differed from those of the controls in 84% of the samples. There was evidence of a disturbance of in vitro monocyte maturation. Also notable was the pattern of interleukin-1ß (IL-1ß) expression by unstimulated monocytes; the basal level of cytokine expression was higher in 71% of patients tested (n=14), indicating chronic stimulation by an unknown event. Moreover, tumour necrosis factor-a (TGFa) expression was higher in half of the patients (n=14) compared to the controls.
The proportional increase of Il-ß and TGFa following stimulation with lipopolysaccharide (LPS) was lower for the majority of patients, suggesting that the monocytes from people with CFS were less responsive to LPS than the healthy controls. This may reflect abnormalities associated with in vitro monocyte maturation.
Marcusson, JA., Lindh, G and Evengard, B. Chronic fatigue syndrome and nickel allergy. Contact Dermatitis, 1999, 40, 5, 269-272.
Fifty patients with CFS (CDC criteria '94) and 73 controls with no history of metal allergy or fatigue, were patch tested with 8 metal allergens.
There was an overrepresentation of allergies among the CFS patients, but this was not significant. An allergy to nickel was found in 36% of patients in the CFS group and in 19% of subjects in the control group (p<0.05). The high frequency of nickel allergy was more noteworthy in females with CFS than among female controls (52% and 24%, respectively, p<0.05). In the males the rates were 14% and 9%.
The researchers suggest that in vivo immunoactivation by ions of nickel, or metal cross-reacting with nickel, could be an aetiological factor in CFS.
Behan, WMH., Holt, IJ., Kay, DH and Moonie, P. In vitro study of muscle aerobic metabolism in chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 3-16.
Study comparing 16 patients with CFS (CDC '94 criteria, all post-exertional fatigue) with 10 healthy controls.
Biopsies were taken from the vastus lateralis muscle and myoblast cultures were established.
Myoblasts from 10 of the 16 patients had defects in aerobic metabolism; two had increased lactate/pyruvate (L/P) ratios, suggestive of a defect in oxidative phosporylation. Eight had decreased ratios, consistent with a deficiency in pyruvate dehydrogenase. There was a statistically significant broader range of L/P ratios in the patients' cultures, compared to controls.
"This in vitro study confirms that there is convincing evidence of mild aerobic defects in skeletal muscle in some cases of CFS".
Himmel, PB and Seligman, TM. A pilot study employing dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. Journal of Clinical Rheumatology, 1999, 5, 2, 56-59.
The purpose of this uncontrolled, prospective, 6 month study of 116 women aged 35-55 was to identify patients with CFS (CDC criteria '88) who had suboptimal serum levels of DHEA-sulphate (DHEA-S), defined as DHEA-S <2.0 µg/mL, and to treat those patients with oral DHEA.
DHEA-S levels were measured again after 4-6 weeks of oral DHEA therapy (25 mg). If DHEA-S remained low or if no clinical response was achieved after 4-6 weeks of therapy, then an increased dose of DHEA was given (up to 100 mg). Physical and psychological impairment and disability status were measured by the MHAQII before DHEA intervention and at 3-month intervals.
Of the initially screened patients with CFS, 89% (103 of 116) had suboptimal production of DHEA-S. Supplementation with DHEA to 23 CFS patients led to a significant reduction in the symptoms of CFS: pain (improved by 18%, p=0.035), fatigue (decreased by 21%, p=0.009), activities of daily living (improved by 8.5%, p=0.058), helplessness (decreased by 11%, p=0.015), anxiety (decreased by 35%, p<0.01), thinking (improved by 26%, p<0.01), memory (improved by 17%, p<0.05), and sexual problems (improved by 22%, p=0.06) over the period of the trial. The main side-effect was acne. "Further study is necessary to determine the safety and efficacy of supplementation of DHEA to this population in a controlled setting."
See also Scott et al below.
LaManca JJ., Peckerman A., Walker J., Kesil, W., Cook S., Taylor A and Natelson BH. Cardiovascular response during head-up tilt in chronic fatigue syndrome. Clinical Physiology, 1999, 19, 2, 111-120.
The researchers compared 39 patients with CFS (CDC criteria '88 and '94) and 31 healthy, sedentary controls for cardiovascular response to orthostatic [postural] challenge, and incidence and mechanisms of neurally mediated hypotension in CFS during a head-up tilt test.
They found that: "there are baseline differences in the cardiovascular profiles of CFS patients when compared with control subjects and that this profile is maintained during head-up tilt". However, the frequency of positive tilts and the haemodynamic adjustments made to this orthostatic challenge were not different between the groups. (Positive tilt tests were noted in 11 CFS patients and 12 controls). The researchers conclude that outcome of a head-up tilt test cannot be used to make or support a diagnosis of CFS.
Scott, LV., Salahuddin, F., Cooney, J., Svec, F and Dinan, TG. Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. Journal of Affective Disorders, 1999, 54, 1-2, 129-137.
This study examined cortisol levels as well as levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone. The subjects were 15 patients with CFS (CFS criteria '94, no current psychopathology), 15 people with major depression and 11 healthy controls.
DHEA and DHEA-S levels were significantly lower in the CFS patients compared to the healthy controls; DHEA-S levels, but not DHEA, were lower in the people with depression while cortisol and 17-alphahydroxyprogesterone did not differ between the three groups. The cortisol:DHEA-S ratio was significantly greater in the CFS group compared to the controls.
The researchers hypothesise that the findings in the CFS group may relate to the reduced size of the adrenal gland (cf. Teh et al 1998). "A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested".
Ax, S. Coping differences between chronic fatigue syndrome sufferers and their carers. Journal of Chronic Fatigue Syndrome, 1999, 5, 2, 27-62.
A study of 155 patients with CFS (no criteria) and 95 carers. All were sent a copy of the Ways of Coping Questionnaire, modified for use by British CFS/ME patients.
There were no gender differences in terms of strategies used by patients. There were also no differences between patients with and without a carer. However, carer husbands used fewer coping strategies than female carers. Patients used both emotion focused and problem focused strategies.
Barsky, AJ and Borus, JF. Functional somatic syndromes. Annals of Internal Medicine, 1999, 130, 11, 910-921.
This review suggests that CFS has much in common with functional somatic disorders, defined here as syndromes "characterized more by symptoms, suffering, and disability than by consistently demonstrable tissue abnormality." However, the main body of the text is more specific, giving the impression that it may be more accurately conceptualised as a variant of somatisation disorder, where "benign symptoms and self-limited conditions" are amplified and reattributed to external factors (viruses, toxins etc.). This phenomenon is reinforced by media publicity, sympathetic physicians, special clinics, litigation and "hotlines". Chronicity is associated with secondary gains. The conclusion acknowledges the suffering and distress associated with these conditions and argues for a more accurate and sophisticated model of these syndromes (i.e. one that includes biological and psychological factors).
[Ed. note. The arguments in this paper rely heavily on other people's opinions, e.g. Elaine Showalter. The authors stereotype patients (cf. Showalter, Shorter) and portray them in a uniformly negative light (highly suggestible, misguided, influenced by litigation, not very sensible). They ignore or distort research evidence; a trend also evident in other recent articles by psychiatrists (e.g. Henningsen and Priebe 1999, Reid and Wessely 1999, Lynch and Clare 1999). Quite simply, it's terribly biased.The authors also consistently refer to articles on fatigue when focusing on CFS. Medical explanations for CFS are dismissed as premature, although this does not apply to theories relating to phobic avoidance etc. If one study suggests a psycho-social influence, the authors imply that this is relevant to all patients with these syndromes. They also argue that their theory is supported by the effectiveness of CBT.
The articles which formed the basis for this paper were identified through Medline ("1966 to the present"), although the search seems to have missed all the studies and reviews suggesting that biological factors play a major role. Or for that matter, the various studies challenging the effectiveness of CBT.
This revisionist article provides further support for the introduction of evidence-based psychiatry. Comments made in the MCCSQ in relation to the editorial by Henningsen and Priebe and the book by Showalter apply here as well.*]
Buckley, L., MacHale, SM., Cavanagh, JTO., Sharpe, M., Deary, IJ and Lawrie, SM. Personality dimensions in chronic fatigue syndrome and depression. Journal of Psychosomatic Research, 1999, 46, 4, 395-400.
The researchers examined personality dimensions in 30 nondepressed patients with CFS (CDC criteria '94), 20 patients with major depressive disorder (MDD) and 15 healthy controls.
On the Revised NEO Five-Factor Inventory (NEO-FFI), patients with CFS scored significantly lower than healthy controls on the extraversion subscale. On the neuroticism dimension of the Eysenck Personality Questionnaire (EPQ), patients with MDD scored higher than those with CFS, who in turn scored significantly higher than the healthy controls. CFS patients rated themselves as higher on neuroticism and less extroverted when ill than when they were well (for neuroticism: 12.7 versus 8.7; for extraversion: 9.0 versus 13.8 respectively).
"Our results suggest that high scores on neuroticism and low scores on extraversion in CFS could be a reaction to chronic illness".
[Ed. note: an earlier study by Goudsmit compared 40 patients with physician-diagnosed ME and 50 people with multiple sclerosis (MS) on a similar measure (EPI). The ME group had a mean neuroticism score of 12 while the MS group had a score of 13.25. The mean for the 40 healthy controls was 10.1.Splitting the group according to duration of illness (<5 years versus>10 years) showed that those who had been ill longer had a higher neuroticism score (14.75 versus 10.84, NS). On the extraversion scale, the ME group scored 11.85, the MS group scored 10.33 and the healthy controls scored 12.55. These results could not be published in medical journals due to unwillingness of editors to accept papers on ME.]
Crowe, SF and Casey, A. A neuropsychological study of the chronic fatigue syndrome: support for a deficit in memory function independent of depression. Australian Psychologist, 1999, 34, 1, 70-75.
This study examined cognitive functioning in CFS after the effects of depression had been partialled out. Twenty-six people with CFS (criteria consistent with Oxford guidelines, recruited from a CFS/ME support group) and twenty-six matched controls were compared on measures including the Chronic Fatigue Symptom Checklist, the Illness Behaviour Questionnaire (IBQ), the Beck Depression Inventory (BDI), Performance IQ from the WAIS-R and the Rey Auditory Verbal Learning Test (RAVLT). The measures of attention and concentration included the Digit Span Test, the Paced Auditory Serial Addition Test (PASAT), and Simple and Choice Reaction Time.
The CFS group were impaired on various measures, particularly those assessing new verbal learning (RAVLT) and choice reaction time. The scores on the PASAT were correlated with depression as well as scores on the IBQ. Once the effects of depression had been partialled out, the significantly lower performance on the RAVLT persisted.
"This indicates that a pattern of impairment characteristic of this group has been observed and supports the notion of central nervous system compromise in these participants." The findings also support previous reports on specific deficits, but undermine the view that CFS is a type of depression.
Green, J., Romei, J and Natelson, BH. Stigma and chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1999, 5, 2, 63-75.
Questionnaires assessing stigma, satisfaction with intimate relationships, reliance on household members, symptoms and labelling of symptoms by doctors were completed by 45 patients with CFS (CDC criteria '88 and '94 with additions).
Most of the patients (95%) had feelings of estrangement, 70% believed that others attributed their symptoms to psychological causes, 77% tried to educate others about CFS (disclosure) while 39% felt a need to be secretive about their illness.
Most subjects were labelled as psychological cases (77%) by one or more physicians but the tendency to attribute to psychological causes was far less among non-medical practitioners (4% affecting 8% of patients). Significantly more male doctors labelled symptoms as psychological. Disclosure was correlated with the physician's labelling of symptoms. Stigma was linked with a longer duration of illness and with the severity of symptoms.
Doctors reconstructed reality to signify that the illness of the patient was "not real". They played a potentially damaging role in delegitimising the illness experience. There was also a subtle infantalization of patients.
The researchers suggest that cumulative interactions with sceptics have a greater influence on stigmatisation than physicians.
Theorell, T., Blomkvist, V., Lindh, G and Evengard, B. Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a non-specific life crisis. Psychosomatic Medicine, 1999, 61, 3, 304-310.
The purpose of this study was to describe the sequence of psychosocial events and infections preceding the onset of CFS. Information was also obtained about the relationship between onset and the development of cardinal symptoms, namely, fatigue, sadness, irritability, pain, and fever.
A personal interview was conducted in 46 patients with CFS (CDC criteria '94, severity unclear). These patients were matched with regard to age and gender to 46 carefully matched control subjects. The patient at first identified the month that coincided with the onset of CFS. Similarly, each control subject was asked to identify a "very difficult period" within approximately the same period as the patient with whom the control subject was matched. A list of 14 different life events was perused. Participants were asked to identify for each month whether each of the listed events had occurred. Furthermore, they were asked to rate the importance of the events they had experienced. In addition, for each of the cardinal symptoms (fatigue, sadness, irritability, pain, and feeling of fever) and for each month, the subjects were asked to rate, on a visual analogue scale, the symptom intensity. Also, the number of infections was noted. The onset of CFS occurred between 12 months and 13 years before the interview.
A statistically significant group difference in fatigue intensity existed during the period 4 to 10 months before the onset or diagnosis of CFS. During the 3 months preceding the diagnosis for the CFS patients or the peak of the crisis for the control group, there was a dramatic rise in fatigue in both groups. The CFS group reached a much higher fatigue level, which levelled off somewhat during the first year of follow-up but still remained very high in comparison with the control group, which reached precrisis levels 4 months after the peak. Similar patterns were observed for fever and pain. With regard to sadness and irritability, no group difference was observed during the period preceding the crisis.
For infections, the prevalence increased successively during the four quarters preceding CFS. There was no significant excess of negative life events during the year, although there were more cases of separation and changes in job responsibility and there was an increase in number of events during the last quarter before the onset of CFS.
The differences between the groups in fatigue, pain and feeling of fever during the months preceding the crisis may be related to the increased number of infections. Alternatively, the life events may have increased the patients' vulnerability to CFS. It is of interest that there were no pre-illness group differences in depressive and irritable feelings. "These findings must be replicated in longitudinal studies."
Tiersky, LA., Cicerone, KD., Natelson, BH and DeLuca, J. Neuropsychological functioning in chronic fatigue syndrome and mild traumatic brain injury: a comparison. Clinical Neuropsychologist, 1998, 12, 4, 503-512.
Thirty people with CFS (CDC criteria '88 and '92 plus modifications), 33 individuals who had sustained a mild traumatic brain injury with postconcussive symptoms (MTBI) and 20 healthy controls who were age and education-matched, were compared on measures of complex information processing, attention/concentration, memory and higher-order cognitive processes.
MTBI and CFS patients demonstrated a similar deficit in complex information processing and verbal learning. Overall, however, individuals who suffered a MTBI demonstrated a greater degree of impairment than did individuals with CFS, who in turn performed less well than healthy controls.
Natelson, BH., Denny, T., Zhou, XD., LaManca, JJ., Ottenweller, JE., Tiersky, L., DeLuca, J and Gause, WC. Is depression associated with immune activation? Journal of Affective Disorders, 1999, 53, 2, 179-184.
Blood was taken from 30 patients with CFS (CDC criteria '88 plus additions), all of whom also suffered from major depression following illness onset, 21 people suffering from major depression alone and 87 healthy, sedentary controls. Subjects also completed the Centers for Epidemiological Study-Depression (CES-D) questionnaire and a fatigue measure.
CES-D scores were high in both patient groups and did not differ significantly. The researchers found no evidence for immune activation in either patient group. Instead the data suggested immunological downregulation in those with depression.
The researchers note that earlier findings of immune activation in depressed patients were limited to individuals with melancholic depression and suggest that the results may have been an epiphenomenon (e.g. due to the stress of hospitalisation?). The differences between the CFS and depressed groups indicate that "depression in CFS reflects a different psychopathological process than in depression without CFS".
Wagner-Raphael LI., Jason LA and Ferrari JR. Chronic fatigue syndrome, chronic fatigue, and psychiatric disorders: predictors of functional status in a national nursing sample. Journal of Occupational Health Psychology, 1999, 4, 1, 63-71.
A study of 71 nurses with chronic fatigue lasting at least one month identified 32 with CFS (CDC criteria '94). Questionnaires assessed fatigue, pain, quality of life, physical, role and social functioning. They were also examined for psychiatric illness (DIS).
Statistical analysis showed that as fatigue increased, quality of life was reduced. Nurses with CFS reported a lower quality of life than nurses with chronic fatigue. Patients with CFS also had higher fatigue scores than nurses with chronic fatigue. The findings support the view that CFS is a distinct entity and not the "arbitrarily defined end of a spectrum of severity".
Reyes, M., Dobbins, JG., Nisenbaum, R., Subedar, NS., Randall, B and Reeves, WC. Chronic fatigue syndrome progression and self-defined recovery: evidence from the CDC Surveillance System. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 17-27.
A group of 155 patients with CFS (CDC criteria '88 at enrolment, duration median 4.4. years) were interviewed. It was estimated that the probability of recovery amongst these patients was 31.4% during the first 5 years and 48.1% during the first ten years. Sudden onset cases (33.5% of the total sample) differed from gradual onset cases in terms of having more symptoms at onset, more infection related symptoms, cognitive dysfunction and depression. As the illness progressed, these differences disappeared although the gradual onset group reported more hypersomnia. After 15 years, the gradual onset cases had higher recovery probabilities. After reporting recovery, 25% subsequently relapsed.
Hickie, I. Nefazodone for patients with chronic fatigue syndrome Australian and New Zealand Journal of Psychiatry, 1999, 33, 2, 278-280.
Ten patients with CFS (CDC criteria '94) presenting for assessment by a specialist psychiatrist were treated with nefazodone. They were also advised to engage in appropriate behavioural and sleep-wake cycle strategies to improve their level of functioning. Four had a history of affective disorder, six had concurrent major depression. Mean duration of treatment was 20.8 (4-40) weeks.
Of the 10 patients, eight reported at least some improvement in the key symptom of fatigue, with four (40%) reporting moderate or marked symptom relief. Additionally, sleep disturbance and mood were both moderately or markedly improved in seven and eight of the patients, respectively. Five of the patients achieved at least a moderate improvement in overall functional outcome and were able to return to work or their previous level of role function. The mean dose of nefazodone was 370 mg/day (range: 200-800 mg), with a strong preference for nocturnal dosing. The drug was introduced slowly (initially 50 mg at night). Seven of the patients had previously failed to respond to moclobemide, while seven had previously failed to respond to conventional antidepressant therapy.
"Nefazodone appears to be worthy of further systematic investigation in patients with CFS."
Buskila, D. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Current Opinion in Rheumatology, 1999, 11, 119-126.
Short review which includes a discussion of some of the most interesting research on fibromyalgia and CFS.
Fischler, B. Review of clinical and psychobiological dimensions of the chronic fatigue syndrome: differentiation from depression and contribution of sleep dysfunctions. Sleep Medicine Reviews, 1999, 3, 2, 131-146.
This short review emphasises the research by psychiatrists and classifies CFS as a somatoform disorder. The author concludes that a classical conceptualisation of masked or somatised expression of depression is no longer tenable. He suggests that sleep disorders play an important role which deserves further study.
[Ed. note: this review gives an out-of-date and thus rather misleading view of the research into immunological factors, muscle dysfunction and other non-psychiatric factors.]
Marshall, GS. Report of a workshop on the epidemiology, natural history, and pathogenesis of chronic fatigue syndrome in adolescents. Journal of Pediatrics, 1999, 134, 4, 395-405.
Review of the research relating to adolescents with CFS.
Anderson, R. Pilot study using the experience sampling method (ESM) with a group of chronic fatigue syndrome (CFS) patients (Meeting Abstract). Australian and New Zealand Journal of Psychiatry, 1999, 33 (Suppl.), A32.
ESM is a method of sampling cognitions which avoids the problems of retrospective recall. Subjects record their activities, moods and cognitions in a diary at ten random intervals per day over a five-day period. CFS patients were more amenable to ESM than depressed subjects.
The data showed that patients with CFS were more fatigued but less sad than two other groups (unspecified) but none of the measures distinguished between CFS and CFS-depressed subjects.
Baschetti, R. Cortisol deficiency may account for elevated apoptotic cell population in patients with chronic fatigue syndrome. Journal of Internal Medicine, 1999, 245, 4, 409-410.
Letter suggesting that hypocortisolism may explain the immunological abnormalities and enhanced apoptosis found in patients with CFS.
In his reply (p. 410), Vojdani discusses the possible role of infectious agents, which Baschetti dismissed. However, given that similar abnormalities were also documented in other patient populations (e.g. patients exposed to toxic chemicals), he agrees that other factors may be important. Thus the cause of apoptosis in these patients remains unclear.
Bohr, T. Sociomatics and illness in CFS. Psychosomatic Medicine, 1999, 61, 256.
Letter implying that CFS is a somatoform disorder.
[Ed. note: this author expresses extreme views. It is noteworthy because it illustrates the continuing hostility of some clinicians, as well as the misinformation and prejudice surrounding CFS.]
Brunello, N., Akiskal, H., Boyer, P., Gessa, GL., Howland, RH., Langer, SZ., Mendlewicz, J., de Souza, MP., Placidi, GF., Racagni, G and Wessely, S. Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas. Journal of Affective Disorders, 1999, 52, 275-290.
Consensus statement including section by Simon Wessely (p. 283-285). He notes that "dysthymia is possibly related to chronic fatigue rather than CFS". Regarding CFS, neurasthenia and dysthymia, he suggests that "a population perspective is likely to conclude that all three lie in dimensional space on an axis somewhere between anxiety and depression".
[Ed. note: readers who are interested in the classification of diseases might like to compare Prof. Wessely's view in this article with that expressed in Reid and Wessely. See below.]
Goudsmit, EM. A response to Lynch and Clare. Modern Medicine of Ireland, 1999, 29, 7-8, 67-69.
Letter criticising a review by Lynch and Clare (ibid.), 1999, 29, 5, 22-24.
Scadding, JG. Fatigue syndromes. Quarterly Journal of Medicine, 1999, 92, 5, 293-294.
Letter noting that the findings relating to post-Q-fever fatigue syndrome do not necessarily apply to other cases of CFS. Moreover, if there is evidence of a causal factor, the subset should be acknowledged in the name. The author disapproves of the term ME, regarding it as inaccurate.
[Ed. note: the author suggests a lack of evidence for an inflammatory process in ME. For details of the relevant literature, see Introduction and Factsheets on Axford's Abode]
Denborough, P., Kinsella, S., Stevens, J and Lubitz, L. Psychological correlates in adolescents with chronic fatigue syndrome (Meeting Abstract). Australian and New Zealand Journal of Psychiatry, 1999, 33, (Suppl.), A33.
A battery of psychometric tests were administered to 22 adolescents with CFS (not defined) before and following an inpatient rehabilitation programme (see also Lubitz et al, below). Significant improvements were found for depression, self-esteem, affective involvement and behavioural control.
Dunstan, RH., McGregor, NR., Butt, HL and Roberts, TK. Biochemical and microbiological anomalies in chronic fatigue syndrome: the development of laboratory based tests and the possible role of toxic chemicals. Journal of Nutritional & Environmental Medicine, 1999, 9, 97-108.
Article reviewing some of the research on the heterogeneity of CFS, based on data from laboratory tests.
Endicott, NA. Chronic fatigue syndrome in psychiatric patients: evidence of premorbid anomalous patterns of brain organisation. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 29-45.
A study of patients attending a psychiatrist: 46 with CFS (CDC criteria '92, 89% with lifetime major depression), 92 physically healthy patients and 46 others. They were compared for the presence of anomalous brain conditions or phenomena (ABCP), such as dyslexia, migraine, speech disorder, nail biting, left-handedness, fainting, nausea and vomiting, motion sickness and seizures.
The results suggest that psychiatric patients who subsequently developed CFS had more pre-CFS ABCP than psychiatric patients who did not develop CFS.
Findley, LJ and Cox, DL. Letter. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 127-128.
Letter responding to the study by Essame et al (ibid., 1998, 4, 2, 51-60.)
The authors note that the majority of patients in this study had a co-morbid mood disorder or chronic somatisation disorder (84%). This may have influenced rehabilitation. Moreover, some patients may not have been severely disabled. However, the authors agree with the conclusions drawn by the researchers (e.g. that phobic avoidance and belief in a physical cause hinder a successful outcome.
Goodnick, PJ and Jorge, CM. Treatment of chronic fatigue syndrome with nefazodone. American Journal of Psychiatry, 1999, 156, 5, 797-798.
Letter reporting that nefazodone helped three patients with CFS, particularly with pain and insomnia.
Heap, LC., Peters, TJ and Wessely, S. Vitamin B status in patients with chronic fatigue syndrome. Journal of the Royal Society of Medicine, 1999, 92, 183-185.
Results of tests on 12 patients with CFS (Oxford criteria, 2 working full-time) revealed a functional deficiency of B vitamins, particularly pyridoxine, compared to 18 healthy controls. Low levels of pyridoxine have been associated with depression.
Jason, LA., Melrose, H., Lerman, A., Burroughs, V., Lewis, K., King CP and Frankenberry EL. Managing chronic fatigue syndrome: overview and case study. AAOHN Journal, 1999 47, 1, 17-21.
Short article discussing CFS and the management of fatigue from the perspective of the envelope theory.
Jiaxu, C and Weiyi, Y. Treatment of chronic fatigue syndrome with Chinese medicine. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, 61-65.
Short article discussing the approach to fatigue in China, particularly the use of Chinese herbs.
Laylander, JA. Nutrient/toxin interaction theory of the etiology and pathogenesis of chronic pain-fatigue syndromes. Journal of Chronic Fatigue Syndrome, 1999, 5, 1, part 1: 67-91 and part 2: 93-126.
Hypothesis suggesting that CFS and related disorders (like Gulf War Syndrome and fibromyalgia) may be the result of a relative excess of fluoride and relative deficiency of magnesium.
Lubitz, L., Denborough, P and Lim, T. Chronic Fatigue Syndrome - Long-term outcome following intensive inpatient rehabilitation program (Meeting Abstract) Australian and New Zealand Journal of Psychiatry, 1999, 33, (Suppl.), A32.
Report on a four-week intensive, multidisciplinary, in-patient programme for adolescents with CFS (not defined). Of the 26 patients, 24 felt better though 16 reported some fatigue. They rated the programme as helpful or very helpful in their recovery.
Martin, WJ. Stealth adaptation of an African green monkey simian cytomegalovirus. Experimental Molecular Pathology, 1999, 66, 3-7.
Details of a cytopathic virus isolated from a patient with a CFS-like illness.
See also Martin and Anderson. (Experimental and Molecular Pathology, 1999, 66, 19-30.) This article on a child with neurological and behavioural problems links the latter with a stealth viral infection. It also mentions that this virus induced illness in mice.
Plioplys, AV. Letter. Journal of Chronic Fatigue Syndrome, 1999, 5, 2, 97-98.
Response to Arzomand (ibid., 1998, 4, 59-69.) Plioplys asks whether the different rates of CFS among school attenders in Sutton and Merton might not be related to a difference in socio-economic status and associated variations in diet (particularly salt intake).
Reid, S and Wessely, S. Somatoform disorders. Current Opinion in Psychiatry, 1999, 12, 163-168.
Short paper implying that CFS is a somatoform disorder (SD). Patients with the latter "may selectively perceive bodily sensations and misinterpret them as pathological".
[Ed. note: this paper seems to confuse somatoform disorders with what used to be referred to as psychosomatic conditions. By accepting that the former may have biological substrates, and by ignoring the view that the symptoms of SD generally express emotional distress, the authors extend the concept of SD and make this an even broader category than it was before. The short discussion misrepresents the research into CFS, particularly in relation to CBT and the effects of attribution on outcome.]
Scholey, A., McCue, P., Mackay, I., Moss, M and Wesnes, K. Cognitive defects in chronic fatigue syndrome are reversed by oxygen administration. Paper presented at the BPS conference, Belfast, April 8-11th, 1999. Proceedings of the British Psychological Society, 1999, 7, 2, 137.
In the first study, 20 "confirmed" CFS patients were tested using the Cognitive Drug Research (CDR) computerised assessment battery. On most tests, the impairment in CFS was comparable to that seen in mild to moderate Alzheimer's disease.
In the second study, 16 individuals with CFS inspired either oxygen or air (placebo) and were administered tests from the CDR battery. Following oxygen inspiration, participants showed significantly improved simple and choice reaction times and a trend towards improved word recall. Mood scores were unaffected.
A separate study by Scholey et al (reported on the same page), provides further support for the suggestion that cognitive performance is 'fuel limited'.
Simpson, LO. ME versus CFS. New Zealand Medical Journal, 1999, 112, 1083, 82.
Letter listing some of the reasons why ME (myalgic encephalopathy) should be "considered a sub-section of chronic fatigue syndromes".
Simpson, LO. The outcome for patients with ME in New Zealand. New Zealand Medical Journal, 1999, 112, 1084, 104-105.
Letter discussing the abnormalities in the blood of patients with ME, some of whom were self-diagnosed. The majority had "flat" cells. After two years, over 60% had not recovered. Some reported having benefited from vitamin B12 and evening primrose oil.
Stewart, JM., Gewitz, MH., Weldon, A., Arlievsky, N., Li, K and Munoz, J. Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics, 1999, 103, 1, 116-121.
The researchers investigated the heart rate and blood pressure (BP) responses to 80' head-up tilt (HUT) in 26 adolescents with CFS (CDC criteria '94). The results were compared with responses in a group of adolescents referred for the evaluation of simple faint and to responses in 13 normal healthy control children of similar age.
A total of 4/13 of the controls and 18/26 simple faint patients experienced typical faints with an abrupt decrease in BP and heart rate associated with loss of consciousness.
One CFS patient had a normal HUT. A total of 25/26 CFS patients experienced severe orthostatic symptoms, associated with syncope in 7/25, orthostatic tachycardia with hypotension in 15/25, and orthostatic tachycardia without significant hypotension in 3/25. Acrocyanosis, cool extremities and oedema indicated venous pooling in 18/25. None of the control or simple faint patients experienced comparable acral or tachycardic findings.
The researchers conclude that CFS is highly related to OI in adolescents. The OI of CFS often has heart rate and BP responses similar to responses in the syndrome of orthostatic tachycardia, suggesting that a partial autonomic defect may contribute to symptomatology in these patients.
Various. Low-dose hydrocortisone for chronic fatigue syndrome. Journal of the American Medical Association, 1999, 281, 20, 1887-1889.
Letters responding to McKenzie et al (ibid., 280, 1061-1066). Baschetti (1997) notes that the dosage of hydrocortisone may have been too high since the adrenal insufficiency was mild. He also questions the timing of the second dose (2 p.m.), if the reduction in cortisol levels occurred in the evening. He believes that hydrocortisone plus fludrocortisone may be more beneficial.
Teitelbaum et al (p. 1887-1888) suggest that dosages of 7.5 to 20 mg/d are safe and effective. They describe the results of their own double-blind study which support the use of low dose hydrocortisone for CFS (n=7).
Friedman and Poland (p. 1888) note the mineralcorticoid properties of hydrocortisone. It also induces euphoria so would make anyone feel better. They ask whether a low salt diet may have affected the symptoms.
In their reply (p. 1888-1889), Straus et al explain how they determined the dose but admit that a lower dose may be effective. They add that they are currently assessing the effect of fludrocortisone.
Watson, WS., Chaudhuri, A., McCreath, GT and Behan, PO. A possible cell membrane defect in chronic fatigue syndrome and syndrome X. Chest Pain with Normal Coronary Angiograms, Pathogenesis, Diagnosis and Management. Developments in Cardiovascular Medicine, 1999, 213, 143-149.
Short review discussing the similarities between CFS and syndrome X, and the theory that CFS may be linked to a cell membrane defect.
Wright, B., Williams, C and Partridge, I. Management advice for children with chronic fatigue syndrome: a systematic study of information from the internet. Irish Journal of Psychological Medicine, 1999, 16, 67-71.
The researchers analysed 13 websites providing information for children with CFS. They concluded that few "provide useful management advice" and noted that some of the advice was either contrary to current research evidence or not supported by it.
[Ed. note: The survey did not include this website featuring the ME and CFS Capita Selecta Quarterly.]
Kirk, KM et al. Fatigue as related to anxiety and depression in a community-based sample of twins aged over 50. Social Psychiatry and Psychiatric Epidemiology, 1999, 34, 2, 85-90.
Measures of fatigue, anxiety and depression were administered in self-report questionnaire format to a community-based sample of 2703 Australian twins aged over 50. Factor analysis indicated that a two-factor solution was appropriate and demonstrated a clear separation between fatigue-related and anxiety/depression items.
Pruessner, JC et al. Burnout, perceived stress, and cortisol responses to awakening. Psychosomatic Medicine, 1999, 61, 197-204.
The effects of burnout and perceived stress on early morning free cortisol levels after awakening were investigated in a group of teachers. Previous studies revealed that cortisol levels show a significant increase after awakening.
Sixty-six teachers from local public schools were asked to provides samples of saliva for cortisol analysis on 3 consecutive days. On each day, cortisol levels were measured at the time of awakening and 15, 30, and 60 minutes thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone orally to test glucocorticoid feedback inhibition. Burnout and perceived stress were measured by three different questionnaires. (There's no information about duration of symptoms).
As expected, levels of cortisol increased after awakening. Teachers scoring high on burnout showed lower overall cortisol secretion on all sampling days, and a higher suppression of cortisol secretion after dexamethasone administration. The subgroup with burnout and high levels of perceived stress showed the lowest self-esteem, the highest external locus of control, and the highest number of somatic complaints. Perceived stress was not related to cortisol levels on the first two days, but data from the third day revealed initial suppression of cortisol followed by increased levels during the first hour after awakening after dexamethasone pre-treatment. Thus the effects of burnout and perceived stress on cortisol secretion appear to be independent from each other. The researchers suggest that a key factor differentiating the two may be chronicity and exhaustion.
See also Melamed et al. Journal of Psychosomatic Research, 1999, 46, 591-598. This study assessed non-shift blue-collar workers on one day and found elevated cortisol levels in those with burnout (up to 6 months).
Bartha, L et al. Multiple chemical sensitivity: a 1999 consensus. Archives of Environmental Health, 1999, 54, 3, 147-149.
Updated set of diagnostic criteria for multiple chemical sensitivity, devised by a group of specialists.
Bell, IR et al. Differing patterns of cognitive dysfunction and heart rate reactivity in chemically-intolerant individuals with and without lifestyle changes. Journal of Chronic Fatigue Syndrome, 1999, 5, 2, 3-25.
Study suggesting that people with chemical intolerances are a heterogeneous population.
Ivanyi, B et al. Late onset polio sequelae: disabilities and handicaps in a population-based cohort of the 1956 poliomyelitis outbreak in the Netherlands. Archives of Physical Medicine and Rehabilitation, 1999, 80, 687-690.
This study of polio survivors from the community (n=233) revealed an increase in neuromuscular complaints and fatigue in recent years. Fifty-six per cent reported increased muscle weakness compared to the stable period. The findings support the link between chronic overuse of muscles and post polio sequelae.
Bell, DS., Robinson, MZ., Pollard, J., Robinson, T and Floyd, B. A parents' guide to CFIDS. How to be an advocate for your child with chronic fatigue immune dysfunction syndrome. NY: Haworth Press. 1999. Pb. 161pp. $22.00 (outside US). E-mail for orders; getinfo@haworthpressinc.com
Practical guide for parents with a child suffering from CFS/ME. Although the information regarding the education system only applies to America, the book has an excellent description of symptoms and many useful tips about coping with ME and its effects.
* Due to the authors' obvious lack of respect for colleagues with a different view, a draft of these comments was not forwarded for their response (our normal editorial policy).
** The opinions expressed are those of the author and do not necessarily reflect the views of the editorial team.
This issue was compiled by Dr. EM Goudsmit, Dr. A. Macintyre and Mrs S. Howes. We gratefully acknowledge the help and support from Dr. C. Shepherd, the Haworth Press and Mr. D. Axford.
The ME and CFS Capita Selecta Quarterly is funded by donations.
Copyright EM. Goudsmit 1999.
©
Psychologist/Archivist, London.
All rights reserved. This article may not be reproduced without
permission from the author. See the full
copyright
notice.
Be sure to see the many other valuable articles at our Main M.E. Home Page
