Elizabeth A. Young

Bio: Elizabeth A. Young is an academic researcher from University of Michigan. The author has contributed to research in topics: Major depressive disorder & Glucocorticoid. The author has an hindex of 61, co-authored 139 publications receiving 14098 citations. Previous affiliations of Elizabeth A. Young include Salk Institute for Biological Studies & Molecular and Behavioral Neuroscience Institute.

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.

Endogenous Opioids: Biology and Function

Abstract: even less so. It was therefore impossible for the functionally minded neuro­ scientist to design and execute experiments taking this heterogeneity into consideration. Even pharmacological studies with these peptides were difficult to interpret in a physiological framework. In 1982, thanks mainly to the recombinant DNA techniques, we learned that all these peptides belong to three genetically distinct peptide families, as we describe below. We now know a great deal more about their anatomy, and we are beginning to clarify their biosynthetic pathways. Suddenly, we can think in terms of circuits rather than in "humors" or in black boxes. In our study offunction, we can no longer ignore the multiple systems, any more than the student of monoamines can ignore differences between dopaminergic and noradrenergic systems. Less clear, but equally critical, is the issue of multiple opioid receptors. Unquestionably, the heterogeneity exists. What remains to be established is whether each of the three families of opioids has its own receptor, or whether a given family can interact with more than one SUbtype, and each receptor subtype with more than one family. More critical to physiology is whether

Strategies and Methods for Research on Sex Differences in Brain and Behavior

Abstract: Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female's reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.

Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis

Abstract: Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.

Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research.

Abstract: This meta-analysis reviews 208 laboratory studies of acute psychological stressors and tests a theoretical model delineating conditions capable of eliciting cortisol responses. Psychological stressors increased cortisol levels; however, effects varied widely across tasks. Consistent with the theoretical model, motivated performance tasks elicited cortisol responses if they were uncontrollable or characterized by social-evaluative threat (task performance could be negatively judged by others), when methodological factors and other stressor characteristics were controlled for. Tasks containing both uncontrollable and social-evaluative elements were associated with the largest cortisol and adrenocorticotropin hormone changes and the longest times to recovery. These findings are consistent with the animal literature on the physiological effects of uncontrollable social threat and contradict the belief that cortisol is responsive to all types of stressors.

The Prevalence of Comorbid Depression in Adults With Diabetes: A meta-analysis

Abstract: OBJECTIVE —To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS —MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used χ 2 statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS —A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8–2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS —The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Stress and the brain: from adaptation to disease

Abstract: In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.