Moderators of the treatment response to guided self-instruction for chronic fatigue syndrome

Abstract:

OBJECTIVE: The efficiency and efficacy of guided self-instruction for chronic fatigue syndrome (CFS) can be enhanced if it is known which patients will benefit from the intervention. This study aimed to identify moderators of treatment response.

METHODS: This study is a secondary analysis of two randomized controlled trials evaluating the efficacy of guided self-instruction for CFS. A sample of 261 patients fulfilling US Center for Disease Control and Prevention criteria for CFS was randomly allocated to guided self-instruction or a wait list. The following potential treatment moderators were selected from the literature: age, fatigue severity, level of physical functioning, pain, level of depressive symptoms, self-efficacy with respect to fatigue, somatic attributions, avoidance of activity, and focus on bodily symptoms. Logistic and linear regression analyses were used with interaction term between treatment response and the potential moderator.

RESULTS: Age, level of depression, and avoidance of activity moderated the response to guided self-instruction. Patients who were young, had low levels of depressive symptoms, and who had a low tendency to avoid activity benefited more from the intervention than older patients and patients with high levels of depressive symptoms and a strong tendency to avoid activity.

CONCLUSION: Guided self-instruction is exclusively aimed at cognitions and behaviours that perpetuate fatigue. Patients with severe depressive symptom may need more specific interventions aimed at the reduction of depressive symptoms to profit from the intervention. Therefore we suggest that patients with substantial depressive symptoms be directly referred to regular cognitive behaviour therapy.

Copyright © 2013 Elsevier Inc. All rights reserved.

 

Source: Tummers M, Knoop H, van Dam A, Bleijenberg G. Moderators of the treatment response to guided self-instruction for chronic fatigue syndrome. J Psychosom Res. 2013 May;74(5):373-7. doi: 10.1016/j.jpsychores.2013.01.007. Epub 2013 Mar 5. https://www.ncbi.nlm.nih.gov/pubmed/23597323

 

Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients

Abstract:

AIMS: Tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GCH) are the rate-limiting enzymes for the biosynthesis of catecholamines and tetrahydrobiopterin (BH4), respectively. Since catecholamines and BH4 are thought to be involved in the pathophysiology of CFS, we explored the genetic factors that influence CFS development and examined the possible association between the SNPs of the TH and GCH genes and the various characteristics of CFS patients.

MAIN METHODS: After drawing venous blood from CFS patients and controls, genomic DNA was then extracted from whole blood in accordance with standard procedures. Digestion patterns of the PCR products were used for genotyping the SNPs of GCH (rs841; C+243T) and TH (rs10770141; C-824T). We also performed questionnaires consisting of fatigue-scale and temperament and character inventory scale (TCI) to CFS patients.

KEY FINDINGS: Our results demonstrated that the allele differences for the GCH and TH SNPs were not associated with CFS patients. We did find that the GCH gene with the C+243T polymorphism affected harm avoidance, while the TH gene with the C-824T polymorphism affected persistence in the CFS patients. The concept of persistence has been linked to specific personality, such as perfectionism, in CFS.

SIGNIFICANCE: Our results suggest that the biosynthetic pathways of the monoamine neurotransmitters that are mediated by TH and GCH might be associated with the CFS clinical findings, because persistence is one of the typical personality traits observed in CFS and patients with major depressive disorder exhibit a higher harm avoidance score.

Copyright © 2012 Elsevier Inc. All rights reserved.

 

Source: Fukuda S, Horiguchi M, Yamaguti K, Nakatomi Y, Kuratsune H, Ichinose H, Watanabe Y. Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients. Life Sci. 2013 Feb 27;92(3):183-6. doi: 10.1016/j.lfs.2012.11.016. Epub 2012 Dec 13. https://www.ncbi.nlm.nih.gov/pubmed/23246742

 

Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome

Abstract:

BACKGROUND: Previous research has suggested that depressed mood may predict outcome and moderate response to treatment in chronic fatigue syndrome, although findings have differed between studies.

AIMS: To examine potential moderators of response to pragmatic rehabilitation v. general practitioner treatment as usual in a recent randomised trial for patients with chronic fatigue syndrome in primary care (IRCTN74156610).

METHOD: Simple regressions, with weighting adjustments to allow for missing data, were calculated. Demographic, medical and psychological variables, and treatment arm, were entered separately and as an interaction term. The outcome variable in each case was change in Chalder Fatigue Scale scores, from baseline to 1-year follow-up, our primary outcome point.

RESULTS: Longer illness durations predicted poorer outcome across the two treatment arms. For patients allocated to pragmatic rehabilitation compared with those allocated to treatment as usual, higher levels of depressive symptoms at baseline were associated with smaller improvements in fatigue (P = 0.022).

CONCLUSIONS: For patients in primary care with higher levels of depressive symptoms, either more intensive or longer pragmatic rehabilitation, or cognitive-behavioural therapy, may be required in order to show a significant improvement in fatigue.

 

Source: Wearden AJ, Dunn G, Dowrick C, Morriss RK. Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome. Br J Psychiatry. 2012 Sep;201(3):227-32. doi: 10.1192/bjp.bp.111.107474. Epub 2012 Jul 26. http://bjp.rcpsych.org/content/201/3/227.long (Full article)

 

Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression

Abstract:

BACKGROUND: Depression is an inflammatory disorder while many authors declare myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to be a functional disorder. The aim of the present study is to compare inflammatory and cell-mediated immune (CMI) responses between depression and ME/CFS.

METHODS: We measured two proinflammatory cytokines (PICs) in plasma, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), with enzyme-linked immunosorbent assays, and serum neopterin with a radioimmunoassay in controls, ME/CFS and depressive patients.

RESULTS: Plasma PICs were significantly higher in ME/CFS than in depression and higher in both patient groups than in controls. Increased PIC levels in depression were attributable to the presence of fatigue and physio-somatic symptoms. Serum neopterin did not differ significantly between depression and ME/CFS but was higher in both patient groups than in controls. The significant positive correlations between neopterin and either IL-1 or TNF-α were significantly greater in depression than in ME/CFS.

CONCLUSIONS: Since PICs cause depression-like behaviors and fatigue/malaise, we suggest that inflammation may play a role in the pathophysiology of ME/CFS and depression. Increased neopterin also seems to contribute to the pathophysiology of both disorders. This study has detected a shared ‘pathway phenotype’, i.e. disorders in inflammatory and CMI pathways, which underpins both ME/CFS and depression and, therefore, may explain the co-occurrence of both disorders. ME/CFS and depression are discriminated from each other by increased PICs in ME/CFS and differences in the immune cell communication networks.

Copyright © 2012 S. Karger AG, Basel.

 

Source: Maes M, Twisk FN, Ringel K. Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom. 2012;81(5):286-95. doi: 10.1159/000336803. Epub 2012 Jul 20. https://www.ncbi.nlm.nih.gov/pubmed/22832503

 

Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

METHODS: This paper reviews the evidence that such symptoms are organically based. We use the term “physio-somatic” to describe these symptoms.

RESULTS: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.

CONCLUSIONS: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated “pathway phenotype”. These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Anderson G, Maes M, Berk M. Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome. Med Hypotheses. 2012 Jun;78(6):752-6. doi: 10.1016/j.mehy.2012.02.023. Epub 2012 Mar 23. https://www.ncbi.nlm.nih.gov/pubmed/22445460

 

Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study

Abstract:

In addition to fatigue, many patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain. We aimed at examining the role of catastrophizing, coping, kinesiophobia, and depression in the chronic pain complaints and in the daily functioning of CFS patients.

A consecutive sample of 103 CFS patients experiencing chronic widespread musculoskeletal pain completed a battery of questionnaires evaluating pain, daily functioning, and psychological characteristics (depression, kinesiophobia, pain coping, and catastrophizing).

Thirty-nine patients participated in the 6-12-month follow-up, consisting of questionnaires evaluating pain and pressure pain algometry. Correlation and linear regression analyses were performed to identify predictors. The strongest correlations with pain intensity were found for catastrophizing (r = -.462, p < .001) and depression (r = -.439, p < .001). The stepwise multiple regression analysis revealed that catastrophizing was both the immediate main predictor for pain (20.2%) and the main predictor on the longer term (20.1%). The degree of depression was responsible for 10% in the observed variance of the VAS pain after 6-12 months.

No significant correlation with pain thresholds could be revealed. The strongest correlations with daily functioning at baseline were found for catastrophizing (r = .435, p < .001) and depression (r = .481, p < .001). Depression was the main predictor for restrictions in daily functioning (23.1%) at baseline. Pain catastrophizing and depression were immediate and long-term main predictors for pain in patients with CFS having chronic widespread musculoskeletal pain. They were also correlated to daily functioning, with depression as the main predictor for restrictions in daily functioning at baseline.

 

Source: Meeus M, Nijs J, Van Mol E, Truijen S, De Meirleir K. Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study. Clin Rheumatol. 2012 Jun;31(6):921-9. doi: 10.1007/s10067-012-1946-z. Epub 2012 Feb 16. https://www.ncbi.nlm.nih.gov/pubmed/22349876

 

Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey

Abstract:

OBJECTIVE: To assess the accuracy of diagnoses made by referrers to a chronic fatigue syndrome (CFS) service.

DESIGN: Retrospective service evaluation surveys of both rejected referral letters and medical case-notes after full clinical assessment.

SETTING: A specialist CFS clinic in London, UK.

PARTICIPANTS: In the first survey, we assessed rejected referral letters between March 2007 and September 2008. In the second survey, we ascertained the primary diagnosis made in case-notes of 250 consecutive new patients assessed between April 2007 and November 2008.

MAIN OUTCOME MEASURES: Reasons for rejection of referrals and primary diagnosis in those assessed.

RESULTS: In the first survey, 154 out of 418 referrals (37%) were rejected. Of these, 77 out of the available 127 referrals (61%) had a likely alternative diagnosis. In the second survey of clinically assessed patients, 107 (43%) had alternative medical/psychiatric diagnoses, while 137 out of 250 (54%) patients received a diagnosis of CFS. The commonest alternative medical diagnoses of those assessed were sleep disorders and the commonest alternative psychiatric diagnosis was depressive illness. Altogether 184 of 377 (49%) patients had alternative diagnoses to CFS.

CONCLUSIONS: Half of all the referred patients to a specialist CFS clinic had alternative medical and psychiatric diagnoses. Specialist medical assessment for patients with unexplained, disabling, chronic fatigue needs to incorporate both medical and psychiatric assessments.

 

Source: Devasahayam A, Lawn T, Murphy M, White PD. Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey. JRSM Short Rep. 2012 Jan;3(1):4. doi: 10.1258/shorts.2011.011127. Epub 2012 Jan 12.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269106/ (Full article)

 

Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression

Abstract:

Patients with chronic fatigue syndrome (CFS) often report a comorbid depressive disorder. Comorbid depression may negatively influence the long-term outcome of CFS therefore it must be correctly diagnosed and treated. The aim of the present study is to provide a clinical and psychometric assessment of CFS patients with and without depressive features.

A comparative analysis between 57 CFS subjects (CDC, 1994), 17 of whom with a comorbid depression, and 55 matched healthy volunteers was assessed to evaluate the presence of any psychophysical distress and alexithymic traits, by means of Symptom Checklist-90-R (SCL-90R) and Toronto Alexithymia Scale (TAS-20). The severity of fatigue was also assessed in all CFS patients using the Fatigue Impact Scale (FIS). With regard to psychiatric comorbidity, the SCL-90R scores showed higher levels of somatic complaints in CFS patients than in healthy subjects, whereas augmented depressive and obsessive-compulsive symptoms were observed only in the depressed CFS subgroup.

When comparing the TAS-20 scores, we observed a selective impairment in the capacity to identify feelings and emotions, as measured by the Difficulty in Identifying Feelings subscale (DIF), non-depressed CFS patients showing an intermediate score between depressed CFS and healthy controls. Finally, in terms of FIS scores, a statistical trend versus a higher fatigue severity in depressed CFS patients, with respect to non-depressed ones, was observed. In conclusion, comorbid depression in CFS significantly increased the level of psychophysical distress and the severity of alexithymic traits. These findings suggest an urgent need to address and treat depressive disorders in the clinical care of CFS cases, to improve social functioning and quality of life in such patients.

 

Source: Sepede G, Racciatti D, Gorgoretti V, Nacci M, Pizzigallo E, Onofrj M, Di Giannantonio M, Niolu C, Salerno RM, Gambi F. Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression. Int J Immunopathol Pharmacol. 2011 Oct-Dec;24(4):1017-25. https://www.ncbi.nlm.nih.gov/pubmed/22230407

 

Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression

Abstract:

BACKGROUND: Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms.

METHODS: We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα.

DISCUSSION: Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Maes M, Mihaylova I, Kubera M, Ringel K. Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):169-75. doi: 10.1016/j.pnpbp.2011.09.006. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/21945535

 

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology

Abstract:

BACKGROUND: There is evidence that depression is accompanied by oxidative and nitrosative stress (O&NS), as indicated by increased free radical levels, lipid peroxidation, and lowered antioxidant levels. The aims of the present study are to examine whether depression is accompanied by autoimmune responses directed against a) neoepitopes that are formed following O&NS damage; and b) the major anchorage molecules, i.e. palmitic and myristic acids and S-farnesyl-L-cysteine.

METHODS: We examined serum IgM antibodies to the conjugated fatty acids, palmitic and myristic acids; acetylcholine; S-farnesyl-L-cysteine; and NO-modified adducts in 26 depressed patients and 17 normal controls. Severity of depression was measured with the Hamilton Depression Rating Scale and severity of fatigue and somatic (F&S) symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: The prevalences and mean values for the serum IgM levels directed against conjugated palmitic and myristic acids, acetylcholine, S-farnesyl-L-cysteine; and the conjugated NO adducts, NO-tyrosine, NO-phenylalanine, NO-aspartate, NO-histidine, and NO-creatine were significantly higher in depressed patients than in normal controls. The autoimmune responses were significantly related to FF symptoms, such as fatigue and a flu-like malaise, whereas the indicants of nitrosative stress were related to gastro-intestinal and autonomic symptoms.

DISCUSSION: Depression is characterized by IgM-related autoimmune responses directed against a) neoepitopes that are normally not detected by the immune system but that due to damage by O&NS have become immunogenic; and b) anchorage epitopes, i.e. palmitic and myristic acids, and S-farnesyl-L-cysteine. These autoimmune responses play a role in the inflammatory and O&NS pathophysiology of depression and may mediate the cellular dysfunctions that contribute to neuroprogression, e.g. aberrations in signal transduction, cellular differentiation and apoptosis.

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

 

Source: Maes M, Mihaylova I, Kubera M, Leunis JC, Geffard M. IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J Affect Disord. 2011 Dec;135(1-3):414-8. doi: 10.1016/j.jad.2011.08.023. Epub 2011 Sep 17. https://www.ncbi.nlm.nih.gov/pubmed/21930301