Tag: depression

Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression

Abstract:

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients.

Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms ofchronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear.

Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.

 

Source: Wheatland R. Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65(2):287-95. http://www.ncbi.nlm.nih.gov/pubmed/15885924

 

Subjective quality of life in patients with chronic fatigue syndrome

Abstract:

The aim of this study was to (1) assess Subjective Quality of Life (SQOL) of patients with Chronic Fatigue Syndrome (CFS) using a generic concept and to compare the findings with those in groups with mental disorders and healthy subjects, and (2) investigate whether and, if so, to what extent socio-demographic and clinical variables predict SQOL in CFS patients.

Seventy-three patients diagnosed with CFS were randomly selected and interviewed from two specialised clinics. CFS was diagnosed using the Oxford Criteria. SQOL was assessed on the Manchester Short Assessment of Quality of Life (MANSA) and Health-Related Quality of Life (HRQOL) on the Medical Outcome Study Short-Form 36 (MOS) SF-36. A battery of mood and symptom questionnaires, including the Symptom Checklist Questionnaire (SCL-90-R), was administered to assess various aspects of symptomatology as potential predictor variables.

Multiple regression analyses were conducted to identify predictors of SQOL. Overall, SQOL was low in CFS patients and less favourable than in groups with mental disorders and healthy subjects. Satisfaction was particularly low with life as a whole, leisure activities and financial situation. Whilst SQOL was only moderately correlated with HRQOL, the SCL-90-R score, especially SCL-90-R Depression scale score, was the best predictor of SQOL explaining 35% of the variance. HRQOL and generic SQOL appear distinct despite some overlap.

The findings underline that SQOL is significantly disrupted in CFS patients. Depressive symptoms are statistically the strongest ‘predictor’ of SQOL, although the direction of the relationship is not established. These data suggest that treatment of depression associated with CFS, regardless of causation, could help to improve SQOL in CFS patients.

 

Source: Rakib A, White PD, Pinching AJ, Hedge B, Newbery N, Fakhoury WK, Priebe S. Subjective quality of life in patients with chronic fatigue syndrome. Qual Life Res. 2005 Feb;14(1):11-9. http://www.ncbi.nlm.nih.gov/pubmed/15789937

 

Neuropsychiatric sequelae of Nipah virus encephalitis

Abstract:

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome.

Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

 

Source: Ng BY, Lim CC, Yeoh A, Lee WL. Neuropsychiatric sequelae of Nipah virus encephalitis. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):500-4. http://www.ncbi.nlm.nih.gov/pubmed/15616178

 

Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care

Abstract:

OBJECTIVE: Unexplained fatigue syndromes, such as chronic fatigue syndrome and neurasthenia, are strongly associated with depression, but the temporal nature of this association is not clear.

METHODS: The authors examined this issue by using data from the World Health Organization collaborative study of psychological problems in general health care. Three thousand two hundred one subjects from 15 primary care centers in 14 countries were followed up for 12 months. The Composite International Diagnostic Interview was the main instrument used. Odds ratios and their 95% confidence intervals (CI) were calculated using logistic regression models adjusted for sociodemographic variables, physical morbidity and intercenter variability.

RESULTS: Cases of depression were found to have an increased risk of developing a new episode of unexplained fatigue at follow-up with an adjusted odds ratio of 4.15 (95% CI = 2.64-6.54). Similarly, cases of unexplained fatigue were found to have an increased risk of developing a new episode of depression at follow-up with an adjusted odds ratio of 2.76 (95% CI = 1.32-5.78). Further adjustment for subthreshold symptoms at baseline weakened the reported associations, especially between fatigue and development of a new episode of depression, but these remained significant.

CONCLUSIONS: The findings support the view that unexplained fatigue and depression might act as independent risk factors for each other.

 

Source: Skapinakis P, Lewis G, Mavreas V. Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care. Psychosom Med. 2004 May-Jun;66(3):330-5. http://www.ncbi.nlm.nih.gov/pubmed/15184691

 

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

Abstract:

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones.

A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI).

Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05).

Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.

 

Source: Gur A, Cevik R, Nas K, Colpan L, Sarac S. Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.  Arthritis Res Ther. 2004;6(3):R232-8. Epub 2004 Mar 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416440/ (Full article)

 

Post-traumatic stress disorder among patients with chronic pain and chronic fatigue

Abstract:

BACKGROUND: Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD).

METHOD: Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined for their relationship with PTSD.

RESULTS: The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3.4, 95% CI 2.0-5.8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a three-fold increase in the prevalence of PTSD (95% CI 1.5-7.1); conversely, FM patients without MDD showed no increase in PTSD (OR=1.3, 95% CI 0.5-3.2). The components of the CFS criteria were not significantly associated with PTSD.

CONCLUSION: Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.

 

Source: Roy-Byrne P, Smith WR, Goldberg J, Afari N, Buchwald D. Post-traumatic stress disorder among patients with chronic pain and chronic fatigue. Psychol Med. 2004 Feb;34(2):363-8. http://www.ncbi.nlm.nih.gov/pubmed/14982142

 

Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome

 Abstract:

Chronic fatigue syndrome (CFS) is a controversial entity whose cause is unknown. In this study we have explored the possibility that progesterone metabolites may be involved. Plasma levels of the progesterone precursor pregnenolone, progesterone itself, and five ring A-reduced metabolites of progesterone were measured in 20 women with CFS and in 13 age-matched controls.

To minimize the contribution of the ovary, women were either post-menopausal or in the follicular phase of the menstrual cycle (day 4-8), and progesterone levels were all well within the expected range (< or = 3.5 nmol/l). Mean values for progesterone and all of its metabolites were higher in CFS patients, the most marked being a 2.3-fold elevation in isopregnanolone (3beta,5alpha-tetrahydroprogesterone; p < or = 0.001). Progesterone levels were correlated with those of its metabolites, but even after controlling for progesterone by ANCOVA, isopregnanolone levels were still elevated (p < or = 0.001). These elevated levels of isopregnanolone could not be attributed to medications (antidepressants and anxiolytics).

When the CFS patients were divided into two groups according to their Hamilton depression scale ratings, mean (+/-SD) isopregnanolone levels were higher (274+/-160 vs 197+/-119 pmol/l) in the less depressed group (ratings 2-14) than in the more depressed group (ratings 17-28), although this difference did not reach significance. Progesterone levels were negatively correlated with Hamilton depression rating scores (r=-0.56; p<0.01). These results suggest that increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS, and that the pathophysiology of CFS is unlikely to be due to depression.

 

Source: Murphy BE, Abbott FV, Allison CM, Watts C, Ghadirian AM. Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Feb;29(2):245-68. http://www.ncbi.nlm.nih.gov/pubmed/14604604

 

Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review

Abstract:

OBJECTIVE: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior.

METHODS: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study.

RESULTS: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

CONCLUSIONS: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as “common mental disorders” does not seem fully appropriate.

 

Source: Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003 Jul-Aug;65(4):528-33. http://www.ncbi.nlm.nih.gov/pubmed/12883101

 

Atypical depression as a secondary symptom in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has gained prominence since 1988 and a substantial amount of research has been done in this domain. However, it is still regarded as a controversial condition. Moreover, most of the symptoms of CFS itself are non-specific, occurring in many illnesses; some of the symptoms are also common in depression. Indeed, an area of continued controversy and debate involves the diagnostic overlap between CFS and psychiatric disorders. Through anecdotal evidence, atypical depression appears to be common in CFS. Recent developments in psychobiology underscore the role of the acute phase response and its associated sickness behavior in affective disorders. Thus, we hypothesize that atypical depression is sickness behavior rather than an affective disorder as shown by anecdotal evidence in CFS.

 

Source: Van Hoof E, Cluydts R, De Meirleir K. Atypical depression as a secondary symptom in chronic fatigue syndrome. Med Hypotheses. 2003 Jul;61(1):52-5. http://www.ncbi.nlm.nih.gov/pubmed/12781640

 

Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine

Abstract:

OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic fatigue of >6 months duration, and normal school controls on measures of anxiety, depression, somatization, functional disability, and illness attribution.

METHODS: Adolescents referred to Children’s Hospital and Regional Medical Center for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue (n = 97) were compared with a group of healthy controls of similar age and sex from a middle school (n = 32). Subjects completed the Spielberger State-Trait Anxiety Inventory-Trait Form, the Children’s Depression Inventory, the Childhood Somatization Inventory, and estimated the number of school days missed in the past 6 months because of illness. Migraine and fatigued subjects completed an illness attribution questionnaire.

RESULTS: Subjects in the 3 groups were 56% to 70% female and ranged from 11 years old to 18 years old with a mean age of 14.0 +/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not meet full CDC criteria. Adolescents with migraine had significantly higher anxiety scores than those with I-CFS or controls and higher somatization scores than controls. Adolescents with CDC-CFS had significantly higher anxiety scores than those with I-CFS or controls, and higher depression and somatization scores than all other groups. There were significant differences between all groups for school days missed with CDC-CFS more than I-CFS more than migraine more than controls. Parents of adolescents with unexplained I-CFS had significantly lower attribution scores relating illness to possible psychological or stress factors than parents of adolescents with CDC-CFS or migraine.

CONCLUSIONS: Adolescents referred to an academic center for evaluation of unexplained chronic fatigue had greater rates of school absenteeism than adolescents with migraine or healthy controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls and higher depression and somatization scores than migraineurs or controls. Parents of adolescents with I-CFS were less likely to endorse psychological factors as possibly contributing to their symptoms than parents of adolescents with CDC-CFS or migraine.

 

Source: Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics. 2003 Apr;111(4 Pt 1):e376-81. http://www.ncbi.nlm.nih.gov/pubmed/12671155