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Biomedical subjects

M A Demitrack

Publications and source records attributed to M A Demitrack.

At least 19 recordsLinked to original sources
PubMed1998

Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms. Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia). How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function. In order to provide a more refined view of the nature of the HPA dusturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.

Fatigue Syndrome, Chronic↗
PubMed1998

The problem of measurement error in multisite clinical trials.

The implementation of a multisite, randomized, clinical psychopharmacologic trial involves a substantial investment of time and effort on the part of all participants. Because of their complexity, such clinical trials present unique methodological and design challenges. Indeed, it is not uncommon for such studies to conclude with uninterpretable results, due in part to such methodological pitfalls. It has been suggested that clarification of such methodologic dilemmas is one of the most important challenges facing the future of industry-sponsored psychopharmacologic drug development. Among the many factors that may contribute to problematic clinical trial results, error in measuring the phenomena being studied is of particular concern. In this article, we describe the outcome of an intensive series of interrater reliability training sessions for the 17-item Hamilton Depression Rating Scale conducted at the start of a Phase II multisite clinical drug trial. The data underscore the magnitude of error present in such a test setting and provide preliminary evidence for the potential effect of this problem on the detection of clinical change.

Adult↗
PubMed1997

Sleep-onset rapid eye movement after electroconvulsive therapy is more frequent in patients who respond less well to electroconvulsive therapy.

The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.

Adult↗
PubMed1996

Eating pathology, fat avoidance, and serum estradiol concentrations in young women.

OBJECTIVE: Pathological dieting in young women is a continuum of behavior, with bulimia nervosa representing the extreme end of the continuum. This cross-sectional study was conducted to describe the relationship between the degree of eating pathology and dietary intake of college-age women. The relationship between dietary intake and serum estradiol concentrations was also examined. METHOD: We evaluated the dietary intake of 69 women, defined according to degree of eating pathology with a questionnaire instrument. Three-day food records at follicular and luteal phases of one menstrual cycle, and serum estradiol concentrations at approximate menstrual cycle days 6, 21, and 28, were evaluated. RESULTS: Greater degree of eating pathology was associated with significantly lower dietary fat and energy intake (p < .05). A trend for luteal phase energy intake to be related to serum estradiol concentration at day 28 (p = .06) was also observed. DISCUSSION: Fat avoidance may be a useful indicator of increased risk for an eating disorder in young women.

Adult↗
PubMed1996

Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome.

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) fall into the spectrum of what might be termed stress-associated syndromes by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. These illnesses also share perturbation of the hypothalamic-pituitary-adrenal axis and sympathetic stress response systems. In this article, the authors discuss the specific neurohormonal abnormalities found in FM and CFS and potential mechanisms by which dysfunction of neurohormonal stress-response systems could contribute to vulnerability to stress-associated syndromes and to the symptoms of FM and CFS.

Humans↗
PubMed1996

Neurohormonal perturbations in fibromyalgia.

Fibromyalgia (FM) falls into the spectrum of what might be termed 'stress-associated syndromes' by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. Patients with FM exhibit disturbances of the major stress-response systems, the HPA axis and the sympathetic nervous system. Integrated basal cortisol levels measured by 24-hour urine-free cortisol are low. FM patients display a unique pattern of HPA axis perturbation characterized by exaggerated ACTH response to exogenous CRH or to endogenous activators of CRH such as insulin-induced hypoglycaemia. The cortisol response to increased ACTH in these stress paradigms is blunted, as is the the cortisol response to exercise. Functional analysis suggests that FM patients may also exhibit disturbed autonomic system activity. For example, plasma NPY, a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Abnormalities of related neuronal systems, particularly decreased serotonergic activity, may contribute to the observed neuroendocrine perturbations in FM. Finally, other neuroendocrine systems, including the growth hormone axis, are also abnormal in FM patients. Many clinical features of FM and related disorders, such as widespread pain and fatigue, could be related to the observed neuroendocrine perturbations. This hypothesis is supported by the observation that many useful treatments for FM affect the function of these central nervous system centres. Further clarification of the role of neuroendocrine abnormalities in patients with FM, and the relationship of these disturbances with particular symptoms, may lead to improved therapeutic strategies.

Animals↗
PubMed1996

Nutritional characteristics, eating pathology, and hormonal status in young women.

Ovulatory dysfunction is common in patients with eating disorders. However, many women engage in pathologic dieting behaviors without meeting the current diagnostic criteria for anorexia or bulimia nervosa. Clinical eating disorders are only the most extreme form of pathologic eating attitudes and behaviors that are present in many young women. Specific food choices and nutrient intakes may be associated with altered gonadal hormone status of these dieters. This cross-sectional study was conducted to describe the nutritional characteristics of college-aged women defined by their eating attitudes and behaviors with a previously described questionnaire. We evaluated dietary intake, body composition, and selected biochemical indicators in 76 undergraduate women. Serum concentrations of estradiol, progesterone, lipids, and carotenoids were measured on days 6, 21, and 28 of one menstrual cycle. Dietary assessment was based on food records at two 3-d intervals during the cycle. Ovulatory status was definitively determined on the basis of biochemical data for 46 of the women. Increased degree of pathologic dieting was associated with a significantly lower intake of dietary fat (P < 0.02), despite similar mean body mass index and body composition across the eating pathology groups. Serum concentration of alpha-carotene was significantly greater (P < 0.005) in association with a greater degree of eating pathology. With ovulation as a between-group factor, serum lutein concentration and dietary intake of energy and fat differed significantly between groups (P < 0.003). Nutritional characteristics associated with pathologic dieting behavior may also be associated with menstrual irregularities in young women.

Adolescent↗
PubMed1995

Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable.

In brain, most L-tryptophan is metabolized to indoleamines, whereas in systemic tissues L-tryptophan is catabolized to kynurenine pathway metabolites. Among these latter compounds are: quinolinic acid, an N-methyl-D-aspartate receptor agonist; kynurenic acid, an antagonist of excitatory amino acid receptors that also reduces quinolinic acid-mediated neurotoxicity; and L-kynurenine, a possible convulsant. Because the metabolism of L-tryptophan through the kynurenine pathway is dependent upon adequate nutrition, we sought to determine whether the impaired nutrition characteristic of eating-disordered patients might be associated with specific disturbances in this metabolic pathway. Cerebrospinal fluid levels of L-tryptophan, quinolinic acid, kynurenic acid, L-kynurenine, and 5-hydroxyindoleacetic acid were measured in medication-free female patients meeting DSM-III-R criteria for either anorexia nervosa (n = 10) or normal-weight bulimia nervosa (n = 22), studied at varying stages of nutritional recovery. Eight healthy, normal-weight females served as a comparison group. Cerebrospinal fluid levels of kynurenic acid were significantly reduced in underweight anorectics, compared to normal females, but returned to normal values with restoration of normal body weight. Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa. Furthermore, in the eating-disordered patients, kynurenic acid levels in cerebrospinal fluid correlated positively with percent-of-population average body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters.

To test the hypothesis that endogenous opiate peptides selectively influence hedonic response to sweet and high-fat foods, the opiate antagonist naloxone, opiate agonist butorphanol, and a saline placebo were administered by intravenous infusion to 16 obese and 25 normal-weight women. Twenty of the women (10 obese, 10 lean) fulfilled DSM-III-R diagnostic criteria for bulimia nervosa, as determined by psychiatric interview. During drug infusion the women tasted and rated 20 sweetened dairy products and were presented with eight snack foods of varying sugar and fat content. Naloxone suppressed hedonic responses in all subject groups and suppressed the consumption of sweet and high-fat foods in binge eaters, but not in nonbingers. Food intakes of obese women were not affected by naloxone. Butorphanol had no effect on either hedonic response or on food consumption in any group. Although opiate blockade is not a viable strategy for weight reduction in the treatment of obesity, it may be useful in the clinical management of the binge-eating disorder.

Adult↗
PubMed1993

Thyroid function in bulimia nervosa.

Bulimia nervosa is characterized by episodes of binge eating. Bulimic patients have diminished caloric requirements and reduced metabolic rate. Because thyroid function is an important modulator of metabolic rate, we sought to clarify conflicting reports concerning this parameter in bulimic patients. Thyroid indices were examined in 18 bulimics at admission and after 3 weeks of abstinence. Patients had thyroid indices in the normal range at admission but slightly diminished triiodothyronine (T3) compared with control subjects (n = 28). Significant declines in T3 and thyroxine and increases in thyrotropin were noted after 3 weeks of abstinence. At abstinence, T3 was positively correlated with caloric intake, protein, fat, and carbohydrate consumption and inversely correlated with percent ideal body weight. We hypothesize that binge-purge behavior may transiently increase thyroid indices and, consequently, metabolic rate in patients with bulimia nervosa. Furthermore, decreases in T3 following abstinence may be related to diminished caloric consumption or may reflect hypothalamic-pituitary dysregulation in these patients.

Adult↗
PubMed1993

The impact of sexual and physical abuse on eating disordered and psychiatric symptoms: a comparison of eating disordered and psychiatric inpatients.

The authors compared rates of physical and sexual abuse in women with eating disorders (N = 102) and general psychiatric disorders (N = 49). Relationships between sexual abuse and severity of eating disordered and psychiatric symptoms were also examined. While high rates of sexual abuse were found in the eating disordered sample, these rates were not significantly higher than those found in the general psychiatric population. No relationship between a history of sexual abuse and severity of eating disordered symptoms was found. However, within the eating disordered group, sexually abuse subjects reported more severe psychiatric disturbances of an obsessive and phobic nature than nonabused subjects. These findings suggest that while sexually abusive experiences may be related to increased psychological distress, they do not serve to increase eating disordered symptomatology.

Adolescent↗
PubMed1993

Relation of dissociative phenomena to levels of cerebrospinal fluid monoamine metabolites and beta-endorphin in patients with eating disorders: a pilot study.

Dissociation is made manifest by a failure to integrate thoughts, feelings, memories, and actions into a unified sense of consciousness. Although dissociation is presumed to be a special state of consciousness manifested by state-dependent memory and physiology, the psychobiology of dissociation is poorly understood. In this study, we examined cerebrospinal fluid levels of the major monoamine metabolites and beta-endorphin in patients with eating disorders (11 with anorexia nervosa, 16 with bulimia nervosa), while they were acutely ill. Dissociative capacity was measured using the Dissociative Experiences Scale (DES). We provide evidence that neurochemical changes in dopaminergic, serotonergic, and opioid systems may be associated with the clinical expression of dissociation in patients with eating disorders during the acute phase of their illness. These preliminary results are compatible with previous studies of neurochemical disturbances in the eating disorders and suggest that future work in dissociation should specifically include examination of these neurobiologic systems.

Adolescent↗
PubMed1993

Effects of the glucocorticoid antagonist RU 486 on pituitary-adrenal function in patients with anorexia nervosa and healthy volunteers: enhancement of plasma ACTH and cortisol secretion in underweight patients.

To further explore whether the hypercortisolism of anorexia nervosa reflects an alteration in the set point for corticotropin-releasing hormone (CRH) secretion or is a manifestation of glucocorticoid resistance, we examined plasma ACTH and cortisol responses to the competitive glucocorticoid antagonist RU 486 (10 mg/kg, p.o. at 8.00 h) versus placebo (PBO) in 7 healthy female volunteers and 8 patients with DSM-III-R anorexia nervosa, all of whom were studied while underweight [64.3 +/- 2.1% average body weight (ABW), mean +/- SE] and 5 of whom were restudied longitudinally following refeeding (> or = 85% ABW, mean 87.4 +/- 0.4% ABW). Blood samples were obtained from 16.00 to 16.30 h and from 4.00 to 8.00 h following dosing. Underweight anorexics were significantly hypercortisolemic by 24 h urinary free cortisol excretion compared with controls (239 +/- 37 vs. 119 +/- 12 nmol/day, p < 0.01). Both controls and underweight anorexics had robust early morning (4.00-8.00 h) plasma cortisol responses to RU 486 (465 +/- 61 and 719 +/- 49 nmol/l) compared with PBO (370 +/- 52 and 451 +/- 31 nmol/l; p < 0.02 and p < 0.01, respectively). The underweight anorexics showed a significant mean early morning plasma ACTH response to RU compared with placebo (3.28 +/- 0.63 vs. 2.01 +/- 0.24 pmol/l, p < 0.05), while the controls showed a trend toward an increase in mean plasma ACTH after RU (3.11 +/- 0.36 pmol/l) compared with PBO (2.31 +/- 0.41 pmol/l, p < 0.13); plasma ACTH means were greater on the RU day than the placebo day at 20 of 25 sampling points (p < 0.001). However, the increment in ACTH on the RU day compared to the placebo day was greater in the underweight anorexics at the first 20 of 25 consecutive time points of the early morning sampling period (p < 0.001). Moreover, underweight anorexics showed a significant plasma ACTH and cortisol response to RU 486 at 16.00-16.30 h (8-8.5 h following administration), while the controls showed no significant response of plasma ACTH or cortisol at this time. When restudied following weight recovery, anorexic patients showed reductions in 24-hour urinary free cortisol excretion (to 191 +/- 40 nmol/day) which were no longer significantly elevated compared with control values.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings.

The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness "chronic fatigue syndrome." Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.

Adult↗