Tag: depression

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

 

Self-esteem mediates the relationship between maladaptive perfectionism and depression in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) often experience depression which may negatively affect prognosis and treatment outcome. Research has shown that depression in CFS is associated with maladaptive or self-critical perfectionism. However, currently, little is known about factors that may explain this relationship, but studies in nonclinical samples suggest that low self-esteem may be an important mediator of this relationship. The present study therefore examined whether self-esteem mediated the cross-sectional association between maladaptive perfectionism and severity of depression in 192 patients meeting Centres for Disease Control and Prevention criteria for CFS.

Patients completed self-report measures of maladaptive perfectionism, self-esteem, depression, and fatigue. Regression analyses and more direct tests of indirect effects (i.e., the Sobel test and bootstrapping) were used to test for mediation. Congruent with expectations, we found that self-esteem fully mediated the relationship between maladaptive perfectionism and depression in CFS. Findings from this study suggest that self-esteem may explain the link between maladaptive perfectionism and depression in CFS, which may have important implications for the treatment and prevention of depression in these patients.

 

Source: Kempke S, Luyten P, Van Houdenhove B, Goossens L, Bekaert P, Van Wambeke P. Self-esteem mediates the relationship between maladaptive perfectionism and depression in chronic fatigue syndrome. Clin Rheumatol. 2011 Dec;30(12):1543-8. doi: 10.1007/s10067-011-1772-8. Epub 2011 May 17. https://www.ncbi.nlm.nih.gov/pubmed/21584732

 

Self-critical perfectionism, stress generation, and stress sensitivity in patients with chronic fatigue syndrome: relationship with severity of depression

Abstract:

Chronic Fatigue Syndrome (CFS) is a highly disabling disorder that is part of a broader spectrum of chronic pain and fatiguedisorders. Although the etiology and pathogenesis of CFS largely remain unclear, there is increasing evidence that CFS shares important pathophysiological disturbances with mood disorders in terms of disturbances in the stress response and the stress system.

From a psycho-dynamic perspective, self-critical perfectionism and related personality factors are hypothesized to explain in part impairments of the stress response in both depression and CFS. Yet, although there is ample evidence that high levels of self-critical perfectionism are associated with stress generation and increased stress sensitivity in depression, evidence supporting this hypothesis in CFS is currently lacking.

This study therefore set out to investigate the relationship between self-critical perfectionism, the active generation of stress, stress sensitivity, and levels of depression in a sample of 57 patients diagnosed with CFS using an ecological momentary assessment approach.

Results showed, congruent with theoretical assumptions, that self-critical perfectionism was associated with the generation of daily hassles, which in turn predicted higher levels of depression. Moreover, multilevel analyses showed that self-critical perfectionism was related to increased stress sensitivity in CFS patients over a 14-day period, and that increased stress sensitivity in turn was related to increased levels of depression. The implications of these findings for future research and particularly for the development of psychodynamic treatment approaches of CFS and related conditions are discussed.

 

Source: Luyten P, Kempke S, Van Wambeke P, Claes S, Blatt SJ, Van Houdenhove B. Self-critical perfectionism, stress generation, and stress sensitivity in patients with chronic fatigue syndrome: relationship with severity of depression. Psychiatry. 2011 Spring;74(1):21-30. doi: 10.1521/psyc.2011.74.1.21. https://www.ncbi.nlm.nih.gov/pubmed/21463167

 

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways

Abstract:

There is a significant ‘comorbidity’ between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy.

This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2′-5′ oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS.

Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways.

Depression and ME/CFS are not ‘comorbid’ disorders, but should be regarded as ‘co-associated disorders’ that are clinical manifestations of shared pathways.

Copyright © 2010 Elsevier Inc. All rights reserved.

 

Source: Maes M. An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):784-94. doi: 10.1016/j.pnpbp.2010.06.023. Epub 2010 Jul 4. https://www.ncbi.nlm.nih.gov/pubmed/20609377

 

Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness

Abstract:

INTRODUCTION: There is now evidence that major depression is accompanied by an induction of inflammatory and oxidative and nitrosative stress (IO&NS) pathways and by a lowered antioxidant status. Coenzyme Q10 (CoQ10) is a strong antioxidant that has anti-inflammatory effects.

METHODS: This paper examines the plasma concentrations of CoQ10 in 35 depressed patients and 22 normal volunteers and the relationships between plasma CoQ10 and treatment resistant depression (TRD), the severity of illness as measured by means of the Hamilton Depression Rating Scale (HDRS) and the presence of chronic fatigue syndrome (CFS).

RESULTS: We found that plasma CoQ10 was significantly (p=0.0002) lower in depressed patients than in normal controls. 51.4% of the depressed patients had plasma CoQ10 values that were lower than the lowest plasma CoQ10 value detected in the controls. Plasma CoQ10 was significantly lower in patients with TRD and with CFS than in the other depressed patients. There were no significant correlations between plasma CoQ10 and the HDRS.

DISCUSSION: The results show that lower CoQ10 plays a role in the pathophysiology of depression and in particular in TRD and CFS accompanying depression. It is suggested that depressed patients may benefit from CoQ10 supplementation. The findings that lower CoQ10 is a risk factor to coronary artery disease and chronic heart failure (CHF) and mortality due to CHF suggest that low CoQ10 is another factor explaining the risk to cardiovascular disorder in depression. Since statins significantly lower plasma CoQ10, depressed patients and in particular those with TRD and CFS represent populations at risk to statin treatment.

 

Source: Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocrinol Lett. 2009;30(4):462-9. https://www.ncbi.nlm.nih.gov/pubmed/20010493

 

The role of coping in the relationship between depression and illness severity in chronic fatigue syndrome

Abstract:

The self-regulatory model (SRM) proposes that both cognitive and emotional illness representations influence the coping processes adopted in response to an illness.

AIM: This study used the SRM to explore the role of coping in the relationship between depression and self-appraisals of illness severity in a population of patients with chronic fatigue syndrome (CFS).

METHODS: The sample comprised 156 participants, 34 men and 121 women, aged between 18 and 78 yrs, who had been medically diagnosed with CFS. Participants were asked to complete three questionnaires: the Cardiac Depression Scale, Ways of Coping Questionnaire, and Severity Subscale of the Illness Perceptions Questionnaire-Revised.

RESULTS: Analyses revealed that almost 70% of the participants were moderately or severely depressed. Additionally, two particular subscales, social support seeking and positive reappraisals, emerged as positively contributing to self-appraisals of illness severity (beta = 0.20 [p < 0.05] and beta = 0.21 [p < 0.05], respectively), thereby supporting the SRM. Furthermore, results indicated that a combination of depression and coping was a better predictor of illness severity than depression alone, accounting for 22% of the variance compared with 8%, respectively.

CONCLUSIONS: The findings suggest that focusing on depression, and particularly coping styles, during treatment interventions could have important implications for therapeutic interventions. This could lead to better treatment strategies for health professionals who work with patients with CFS.

 

Source: Walker K, Lindner H, Noonan M. The role of coping in the relationship between depression and illness severity in chronic fatigue syndrome. J Allied Health. 2009 Summer;38(2):91-9. https://www.ncbi.nlm.nih.gov/pubmed/19623790

 

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders

Abstract:

AIMS: Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two-year prospective follow-up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders.

METHODS: A total of 155 patients who met the Japanese case definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow-up interview approximately 24 months later.

RESULTS: Of the 70 patients with chronic fatigue syndrome, 33 patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome.

CONCLUSIONS: Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is necessary in addition to the medical treatment given for chronic fatigue syndrome.

 

Source: Matsuda Y, Matsui T, Kataoka K, Fukada R, Fukuda S, Kuratsune H, Tajima S, Yamaguti K, Kato YH, Kiriike N. A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders. Psychiatry Clin Neurosci. 2009 Jun;63(3):365-73. doi: 10.1111/j.1440-1819.2009.01954.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1819.2009.01954.x/full (Full article)

 

Does depression mediate the relation between fatigue severity and disability in chronic fatigue syndrome sufferers?

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is often associated with significant levels of disability. Although fatigue and depression have been found to be independently related to severity of disability, it is not clear how these three factors are mutually related. The present study sought to address this issue by specifically testing a model of mediation whereby depression was hypothesized to influence relations between fatigue and disability.

METHODS: Participants included 90 individuals seeking treatment for CFS at a tertiary care facility. Each provided demographic information and completed standardized measures of depression and fatigue severity, as well as a measure of disability, which assessed difficulties in physical, psychosocial, and independence domains.

RESULTS: Analyses indicated that depression and fatigue were positively correlated with one another, as well as all three disability domains. Analyses of mediation indicated that depression completely mediated the relation between fatigue and psychosocial disability and partially mediated the relation between fatigue and the other two disability domains. Indirect effects tests indicated that the inclusion of depression in the statistical models was statistically meaningful.

CONCLUSIONS: These results replicate previous findings that fatigue and depression are independently related to disability in those with CFS. A more complex statistical model, however, suggested that depression severity substantially influenced the strength of the relation between fatigue and disability levels across a range of domains, including complete mediation in areas involving psychosocial functioning. These results may aid in clarifying contemporary conceptualizations of CFS and provide guidance in the identification of appropriate treatment targets.

 

Source: Hadlandsmyth K, Vowles KE. Does depression mediate the relation between fatigue severity and disability in chronic fatigue syndrome sufferers? J Psychosom Res. 2009 Jan;66(1):31-5. doi: 10.1016/j.jpsychores.2008.08.002. Epub 2008 Nov 22. https://www.ncbi.nlm.nih.gov/pubmed/19073290

 

Symptoms, impairment and illness intrusiveness–their relationship with depression in women with CFS/ME

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an illness in which physiological and psychological factors are believed to interact to cause and maintain CFS/ME in an individual predisposed to it. The various symptoms and impairments associated with CFS/ME have a large impact on quality of life. The purpose of the present study was to identify the extent to which the core symptoms and impairments associated with CFS/ME relate to depression in women with CFS/ME, and to discover whether these relationships were mediated by illness intrusiveness. CFS/ME was found to be a highly intrusive illness, intruding into more life domains and to a greater degree than other illnesses. The effects of both symptoms and impairment on depression were, in part, mediated by illness intrusiveness. Although symptoms severity and impairment had both direct and indirect effects on depression, illness intrusiveness was the strongest predictor of depression.

 

Source: Dancey CP, Friend J. Symptoms, impairment and illness intrusiveness–their relationship with depression in women with CFS/ME. Psychol Health. 2008;23(8):983-99. doi: 10.1080/08870440701619957. https://www.ncbi.nlm.nih.gov/pubmed/25160923