Biomedical subjects

M A Demitrack

Publications and source records attributed to M A Demitrack.

45 records · Page 3Linked to original sources

PubMed1989

Effects of glucocorticoid antagonism with RU 486 on pituitary-adrenal function in patients with major depression: time-dependent enhancement of plasma ACTH secretion.

Data from our group and others suggest that pituitary-adrenal activation in major depression reflects a defect at or above the hypothalamus which results in the hypersecretion of corticotropin-releasing hormone (CRH); some have suggested, however, that elevated indices of cortisol secretion and lack of suppressibility to dexamethasone may be a manifestation of a primary defect in glucocorticoid receptor activation. We report here a study of early morning pituitary-adrenal responses to the glucocorticoid antagonist RU 486 in patients with major depression and healthy volunteers. Previous data suggested that the response to RU 486 could represent an index of endogenous CRH secretory activity. RU 486 produced a robust increase in plasma corticotropin (ACTH) and cortisol secretion in both control subjects and depressed patients. In the controls, however, the increase was confined to the last 2 hours of sampling (6 to 8 am), whereas in the depressed patients the increase occurred throughout the sampling period (3 to 8 am). The ACTH response in the depressed patients exceeded that in the controls during most of the sampling period, including a significant (p less than .005) increase between 3 and 4:30 am. These results are compatible with the idea that hypercortisolism in major depression represents an alteration in the overall set point for hypothalamic CRH secretion rather than a primary alteration at the level of the glucocorticoid receptor.

Adrenocorticotropic Hormone↗

PubMed1989

Stress-responsive neurohormonal systems and the symptom complex of affective illness.

The role of stress in the natural history of major depression has been a subject of intense scrutiny, particularly in light of the 20th century discoveries of some of the biological mediators of stress responses. In this paper we present evidence suggesting the hypothesis that an abnormality in the counterregulation of generalized stress responses underlies critical aspects of the pathophysiology of major depression. In particular, we focus on the role of inadequate glucocorticoid restraint of the central nervous system (CNS) components of the adrenocortical and adrenergic systems, i.e. the corticotropin releasing hormone (CRH) components of the adrenocortical and adrenergic systems, i.e. the corticotropin releasing hormone (CRH) and locus ceruleus-norepinephrine (LC-NE) systems. We believe that this hypothesis not only helps explain many of the observed abnormalities in the syndrome of major depression, but also provides a biological basis for subtyping this syndrome.

Humans↗

PubMed1989

Neurohypophyseal dysfunction: implications for the pathophysiology of eating disorders.

Vasopressin (AVP) and oxytocin (OT) are hypothalamic neuropeptides having distinct peripherally and centrally directed cell populations. While principally responsible for the regulation of osmotic equilibrium, AVP also participates in stress-mediated adrenocorticotropic hormone (ACTH) release, and in consolidation and retrieval of aversively conditioned behaviors. OT is principally known for its role in parturition and lactation, but also has effects opposite of AVP, antagonizing stress-mediated ACTH release and impairing the consolidation and retrieval of aversively conditioned behaviors. Our group has demonstrated novel peripheral osmoregulatory defects in underweight anorexics, coupled with hypersecretion of AVP into the cerebrospinal fluid (CSF). Conversely, a relative reduction of CSF OT is seen in underweight anorexics. Speculatively, these reciprocal changes in neurohypophyseal peptides in the underweight anorexic may enhance the observed neuroendocrine and cognitive abnormalities. In addition, the alterations in CSF OT may occur as a consequence of the abnormal gastrointestinal function present during the acute stages of anorexia nervosa.

Feeding and Eating Disorders↗

PubMed1988

Oxytocin: neurobiologic considerations and their implications for affective illness.

1. Oxytocin is a nonapeptide hormone first isolated in the central nervous system in the supraoptic and paraventricular nuclei of the hypothalamus. Recent studies show that oxytocin is also found in brain regions outside of the hypothalamus and sites of synthesis have been reported in peripheral steroidogenic organs as well. 2. Oxytocin is released from hypothalamic nerve terminals in the posterior pituitary for distribution in the systemic circulation, where it acts to stimulate uterine contraction during parturition and milk let-down during lactation. 3. Although a definitive role for oxytocin in CNS function has not been elucidated, studies in experimental animals suggest involvement in cognition, tolerance and adaptation, and in complex maternal behaviors. Similarly, although oxytocin's function in steroid-producing tissues is not fully established, recent in vitro data has shown that oxytocin can inhibit androgen and estrogen production, and thus may act in a local regulatory fashion. 4. This selective review will highlight some current ideas regarding the functional significance of oxytocin in the central nervous system and review available data concerning the regulation of oxytocin secretion in humans and its potential role in neuropsychiatric illness.

Animals↗

PubMedDate not supplied

Seasonal symptom variation in patients with chronic fatigue: comparison with major mood disorders.

The psychobiology of idiopathic fatigue has received renewed interest in the medical literature in recent years. In order to examine the relation between chronic, idiopathic fatigue and specific subtypes of depressive illness, we characterized the pattern and severity of seasonal symptom variation in 73 patients with chronic, idiopathic fatigue, compared to patients with major depression (n = 55), atypical depression (n = 35), and seasonal affective disorder (n = 16) Fifty of the fatigued subjects also met the specific Centers for Disease Control and Prevention case criteria for chronic fatigue syndrome, though this definition was unable to discriminate a distinct subgroup of patients, based on their seasonality scores alone. As a group, the fatigued subjects reported the lowest levels of symptom seasonality of any of the study groups. Further, even in those fatigued subjects with scores in the range of those seen in patients with seasonal affective disorder, seasonality was not reported to be a subjectively distressing problem. These findings lend support to the idea that although chronic fatigue shares some clinical features with certain mood disorders, they are not the same illnesses. These data are also consistent with the emerging view that chronic fatigue represents a heterogeneously determined clinical condition.

Adult↗

PubMedDate not supplied

Obsessionality in eating-disorder patients: relationship to clinical presentation and two-year outcome.

Obsessionality and obsessive-compulsive symptoms have been regarded as important characteristics in the clinical presentation of the eating disorders. In this report, we examined the relation between obsessionality and the clinical presentation and outcome of a sample of eating-disordered patients. Self-rated obsessional symptoms, defined by the obsessive-compulsive subscale of the Symptom Checklist 90 (revised version), were compared with presenting clinical symptomatology, and scores on the Eating Disorder Inventory (EDI) and Beck Depression Inventory (BDI) in a sample of 110 consecutively evaluated women who met DSM-IIIR criteria for eating disorders. Forty patients were contacted for a follow-up investigation, 2 years after the initial evaluation. Higher obsessive-compulsive subscale scores at presentation were associated with more severe dieting, a greater number of psychiatric hospitalizations, and higher EDI, SCL-90R and BDI scores. Initial obsessive-compulsive scores did not predict the subsequent outcome of a sample of these patients in the community. However, elevated obsessive-compulsive scores obtained at follow-up were associated with the presence of lower body weight and more severe eating-disorder symptoms at that time. These results support the hypothesis that elevated obsessionality is associated with more severe eating disorder symptomatology. In addition, obsessional symptoms change along with those of the eating disorder, and their persistence may be associated with a poorer outcome.

Adolescent↗

PubMedDate not supplied

Neuroendocrine correlates of chronic fatigue syndrome: a brief review.

Chronic fatigue syndrome remains one of the more perplexing syndromes in contemporary clinical medicine. One approach to understanding this condition has been to acknowledge its similarities to other disorders of clearer pathophysiology. In this review, a rationale for the study of neuroendocrine correlates of chronic fatigue syndrome is presented, based in part on the clinical observation that asthenic or fatigue states share many of the somatic symptom characteristics seen in recognized endocrine disorders. Of additional interest is the observation that psychological symptoms, particularly disturbances in mood and anxiety, are equally prominent in this condition. At this time, several reports have provided replicated evidence of disruptions in the integrity of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. It is notable that the pattern of the alteration in the stress response apparatus is not reminiscent of the well-understood hypercortisolism of melancholic depression but, rather, suggests a sustained inactivation od central nervous system components of this system. Recent work also implicates alterations in central serotonergic tone in the overall pathophysiology of this finding. The implications of these observations are far from clear, but they highlight the fact that, though chronic fatigue syndrome overlaps with the well-described illness category of major depression, these are not identical clinical conditions.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Two year follow-up of atypical depression.

The symptom cluster of Atypical Depression (AD) has been characterized based on its presentation and selective response to pharmcological treatments, while relatively little is known about the outcome of these patients after treatment trials. The present study was undertaken to assess the long term outcome of 40 patients after a controlled treatment trial of fluoxetine vs phenelzine. Twenty five of these subjects were interviewed approximately two years after completion of the initial trial. They reported a high frequency of symptom recurrence, but generally little symptomatic or social impairment between episodes. Eighteen subjects were taking antidepressants at follow-up. A higher frequency of depressive episodes was recorded during the times when off antidepressant medications. Overall outcome was rated as moderate or good in the majority of subjects. These results suggest that AD presents from similarities with other subtypes of depression, with high rates of symptomatic recurrence and lasting response to chronic antidepressant treatment. Conversely, social functioning and overall outcome appear more favorable in AD.

Adult↗

PubMedDate not supplied

Carotenoids and menstrual cycle phase in young women.

An association between serum carotenoid concentrations and risk for certain cancers has been observed in epidemiological studies. Determinants of serum carotenoid concentrations are known to include dietary intake, plasma lipid concentrations, and body mass. Menstrual cycle phase, which has not been adequately addressed in previous studies, has been suggested to be a possible additional factor to consider in the interpretation of these values in women. We evaluated hormonal status, serum carotenoids, cholesterol, and triglycerides in 48 healthy women at early follicular, mid-luteal, and late luteal phases of one menstrual cycle. Eating patterns were assessed with diet records at two 3-day intervals during the cycle. Analysis was focused on the 30 subjects who were determined to have ovulated during the menstrual cycle under observation. Serum cholesterol was significantly decreased (P < 0.05) in the late luteal phase of an ovulatory cycle. Lutein concentration was increased in the early follicular phase (P < 0.05) and alpha-carotene was increased in the mid-luteal phase (P < 0.05) only if uncorrected for total cholesterol. Other carotenoids did not vary across the menstrual cycle, whether corrected or uncorrected for total cholesterol concentration. In normal healthy ovulating women, serum carotenoids do not appear to vary with menstrual cycle phase when corrected for serum cholesterol concentrations.

Adult↗