The psychotherapeutic effects of estrogens

Abstract:

The effect of estrogens on the central nervous system, particularly mood and behavior, remains a controversial area which needs clarification, not just for understanding of depression in women but to ensure that such commonplace problems in women have efficient and appropriate therapy.

There is now good evidence that estrogens are rapidly effective in the treatment of depression in many women but this information has not found its way through to those health care personnel, psychiatrists and psychologists who are principally involved in the treatment of depression. There is also strong evidence for the benefits of estrogens on cognitive functioning, not only in preventing the onset of dementia but also in improving the symptoms in the established condition.

Recent work has also suggested a benefit for estrogens on mood in women diagnosed as suffering from chronic fatigue syndrome. This article reviews the effect of endogenous estrogen on the female central nervous system and the ever increasing evidence for the diverse psychotherapeutic effects of exogenous estrogens.

 

Source: Panay N, Studd JW. The psychotherapeutic effects of estrogens. Gynecol Endocrinol. 1998 Oct;12(5):353-65. http://www.ncbi.nlm.nih.gov/pubmed/9859029

 

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome

Erratum in: Br J Psychiatry 1998 Jul;173:89.

 

Abstract:

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments.

METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments.

RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks.

CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Comment in:

Commentary on: randomised, double-blind, placebo-controlled trial of fluoxetine and graded exercise for chronic fatigue syndrome. [Br J Psychiatry. 1998]

Analysis of drop-out data in treatment trials. [Br J Psychiatry. 1998]

Fluoxetine and graded exercise in chronic fatigue syndrome. [Br J Psychiatry. 1998]

 

Source: Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ, Appleby L, Campbell IT, Morris JA. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry. 1998 Jun;172:485-90. http://www.ncbi.nlm.nih.gov/pubmed/9828987

 

Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data

Abstract:

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET).

We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients.

CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas.

CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal.

Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.

 

Source: Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P, Ferlin G. Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. Am J Med. 1998 Sep 28;105(3A):54S-58S. http://www.ncbi.nlm.nih.gov/pubmed/9790483

 

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis

Abstract:

The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses–major depression and multiple sclerosis (MS)–and with data from healthy sedentary controls.

The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables–circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers–the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b-, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3-/CD16+ and CD56+.

Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values-contrary to expectation.

When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS.

These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.

 

Source: Natelson BH, LaManca JJ, Denny TN, Vladutiu A, Oleske J, Hill N, Bergen MT, Korn L, Hay J. Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis. Am J Med. 1998 Sep 28;105(3A):43S-49S. http://www.ncbi.nlm.nih.gov/pubmed/9790481

 

Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression

Abstract:

OBJECTIVES: Patients with chronic fatigue syndrome complain of physical and mental fatigue that is worsened by exertion. It was predicted that the cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would differ from those in depressed and healthy controls.

METHODS: Ten patients with chronic fatigue syndrome, 10 with depressive illness, and 10 healthy controls completed cognitive and muscle strength testing before and after a treadmill exercise test. Measures of cardiovascular functioning and perceived effort, fatigue, and mood were taken during each stage of testing.

RESULTS: Depressed patients performed worst on cognitive tests at baseline. During the treadmill test, patients with chronic fatigue syndrome had higher ratings of perceived effort and fatigue than both control groups, whereas patients with depression reported lower mood. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused (p=0.02) and sustained (p=0.001) attention, as well as greater deterioration than depressed patients on the focused attention task (p=0.03). No between group differences were found in cardiovascular or symptom measures taken during the cognitive testing.

CONCLUSIONS: Patients with chronic fatigue syndrome show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both. Further insight into the pathophysiology of the core complaints in chronic fatigue syndrome is likely to be realised by studying the effects of exercise on other aspects of everyday functioning.

 

Source: Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):541-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/ (Full study)

 

Serum neopterin and somatization in women with chemical intolerance, depressives, and normals

Abstract:

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation.

Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11).

Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of ‘unexplained’ multiple somatic symptoms in subtypes of apparent somatizing disorders.

 

Source: Bell IR, Patarca R, Baldwin CM, Klimas NG, Schwartz GE, Hardin EE. Serum neopterin and somatization in women with chemical intolerance, depressives, and normals. Neuropsychobiology. 1998;38(1):13-8. http://www.ncbi.nlm.nih.gov/pubmed/9701717

 

Depression and short REM latency in subjects with chronic fatigue syndrome

Abstract:

OBJECTIVE: The hypothesized polysomnographic marker for depression, Rapid Eye Movement Latency (REML), was used to investigate two groups of subjects; Chronic Fatigue Syndrome (CFS)-not depressed and CFS-depressed.

METHOD: CFS subjects were classified into depressed and not depressed groups, using the Diagnostic Interview Schedule (DIS), and subsequently were studied in a sleep laboratory to ascertain REML.

RESULTS: Short REML showed a statistically significant correlation with the depressed state in CFS subjects.

CONCLUSION: Short REM latency is associated with depression in the CFS population.

 

Source: Morehouse RL, Flanigan M, MacDonald DD, Braha D, Shapiro C. Depression and short REM latency in subjects with chronic fatigue syndrome. Psychosom Med. 1998 May-Jun;60(3):347-51. http://www.ncbi.nlm.nih.gov/pubmed/9625223

 

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.

METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors.

RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.

CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Comment in: The importance of mental fatigue. [J Neurol Neurosurg Psychiatry. 1998]

 

Source: Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, Natelson BH. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):431-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170049/

 

The importance of mental fatigue

Comment onRelation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1998]

 

The paper by Christodoulou et al in this issue of the Journal (pp 431–4) draws attention to memory deficits in some patients with operationally defined chronic fatigue syndrome, and days of (enforced) physical inactivity. Many studies have assessed cognitive dysfunction in patients with chronic fatigue. The earliest reported superior abilities in such patients against controls or age matched normal subjects, probably reflecting a biased selection of cases from higher socioeconomic groups. Later studies have been the subject of at least two major reviews.1 2

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170046/pdf/v064p00430.pdf

 

Source: Lambert MV, David A. The importance of mental fatigue. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):430. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170046/pdf/v064p00430.pdf (Full article)

 

A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls

Abstract:

BACKGROUND: Previous studies reporting cortisol hyposecretion in chronic fatigue syndrome may have been confounded by venepuncture, fasting and hospitalisation.

METHODS: Morning and evening salivary cortisol were obtained on consecutive days in the first 3 days of the menstrual cycle and compared in three samples of women taking no medication and matched for age: 14 patients with chronic fatigue syndrome, 26 community cases of ICD-10 current depressive episodes and 131 healthy community controls.

RESULTS: The mean evening cortisol was significantly lower in the chronic fatigue syndrome patients compared to controls with depression (P = 0.02) and healthy controls (P = 0.005). Chronic fatigue syndrome patients without psychiatric disorder had significantly lower morning salivary cortisols compared to controls (P = 0.009).

CONCLUSION: Chronic fatigue syndrome patients display cortisol hyposecretion in saliva as well as plasma compared to patients with depression and healthy controls.

LIMITATIONS: Small samples of female patients with cortisol estimated at only two time points in the day. Cortisol secretion may be secondary to other neurotransmitter abnormalities or other physiological or lifestyle factors in chronic fatigue syndrome patients.

CLINICAL RELEVANCE: Chronic fatigue syndrome is biochemically distinct from community depression.

 

Source: Strickland P, Morriss R, Wearden A, Deakin B. A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls. J Affect Disord. 1998 Jan;47(1-3):191-4. http://www.ncbi.nlm.nih.gov/pubmed/9476760