Janet Tarika

Bio: Janet Tarika is an academic researcher from University of Michigan. The author has contributed to research in topics: Dexamethasone suppression test & Endogenous depression. The author has an hindex of 9, co-authored 13 publications receiving 2616 citations.

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Abstract: • Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 ug/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

Plasma Dexamethasone Concentrations and Cortisol Suppression Response in Patients with Endogenous Depression

Abstract: An early escape of plasma cortisol concentrations during a 24-h overnight oral dexamethasone suppression test (DST) has been noted in patients with endogenous depression (ED). Among psychiatric patients this finding is highly specific for ED. Plasma dexamethasone and plasma cortisol concentra- tions were measured in patients with ED and, for comparison, in patients with nonendogenous depression who maintained normal suppression of plasma cortisol during the DST. There was little variation in plasma dexamethasone concentrations between tests within individual patients. In patients with ED tested both before and after treatment the half-life of dexamethasone in plasma between 9-24 h after its administration was the same as that reported by other investigators in normal subjects between 2-8 h after dexamethasone. Abnormally high plasma cortisol concentrations during the DST were observed in patients with ED in association with normal plasma concentrations of dexa- methasone. After treatment, these patients maintained normal suppression of plasma cortisol for 24 h after dexamethasone administration, without any change in their plasma dexametha- sone concentrations. Patients with nonendogenous depression and those who had recovered from an episode of endogenous depression maintained normal suppression of plasma cortisol through 1600 and 2300 h after dexamethasone despite having low plasma dexamethasone concentrations at these times. We conclude that the abnormal escape of plasma cortisol concentra- tions from suppression during the 24-h DST in patients with ED cannot be explained by unusually rapid clearance of dexameth- asone from plasma. The results indicate that a central neuroen- docrine disturbance is present in patients with ED. («/ Clin Endocrinol Metab 51: 433, 1980)

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

Abstract: Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

The Neuroendocrinology of Stress and Aging: The Glucocorticoid Cascade Hypothesis

Abstract: Over the past 5 yr, we have examined some of the sharpest edges of the pathology of aging. We have studied the capacity of aged organisms to respond appropriately to stress and the capacity of stre...

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Abstract: • Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 ug/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression

Abstract: The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The MPFC is part of a larger “default system” of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions. Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans. Further, because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders. This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies.