This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

I. Limbic System-Adrenocortical Dysfunction

Bernard J. Carroll, MB, DPM, PhD; George C. Curtis, MD; Joseph Mendels, MD

Arch Gen Psychiatry. 1976;33(9):1039-1044.

Abstract
• The regulation of hypothalamopituitary-adrenal (HPA) function in depressed patients was studied by a midnight dexamethasone suppression test. By using an observation period of 24 hours postadministration of dexamethasone, a graded series of abnormal test responses was identified. Depressed patients show abnormal early escape from suppression rather than absolute resistance to HPA suppression by dexamethasone. With increasing severity of depression, this escape occurs progressively more early on the day after administration of dexamethasone. These abnormalities were strongly related to the presence of HPA hyperactivity before dexamethasone was given. The essential disturbance of neuroendocrine regulation in depression is a failure of the normal brain inhibitory influence on the HPA system. This disinhibition of HPA activity suggests that there is an abnormal limbic system drive on the HPA axis in primary depressive illness.

Author Affiliations
From the Department of Psychiatry (Drs Carroll and Curtis), University of Michigan, Ann Arbor, and the Department of Psychiatry (Dr Mendels), University of Pennsylvania and Veterans Administration Hospital, Philadelphia.

Footnotes
Accepted for publication April 7, 1976.

Reprint requests to Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109 (Dr Carroll).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Distinct, Time-Dependent Effects of Voluntary Exercise on Circadian and Ultradian Rhythms and Stress Responses of Free Corticosterone in the Rat Hippocampus
Droste et al.
Endocrinology 2009;150:4170-4179.
ABSTRACT | FULL TEXT  

Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity: Results From a Large Cohort Study
Vreeburg et al.
Arch Gen Psychiatry 2009;66:617-626.
ABSTRACT | FULL TEXT  

Pituitary-Adrenal and Sympathetic Nervous System Responses to Stress in Women Remitted From Recurrent Major Depression
Ahrens et al.
Psychosom. Med. 2008;70:461-467.
ABSTRACT | FULL TEXT  

Insulin Resistance, Affective Disorders, and Alzheimer's Disease: Review and Hypothesis
Rasgon and Jarvik
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2004;59:M178-183.
ABSTRACT | FULL TEXT  

The Neuroendocrinology of Chronic Fatigue Syndrome
Cleare
Endocr. Rev. 2003;24:236-252.
ABSTRACT | FULL TEXT  

Impact of Gender, Menstrual Cycle Phase, and Oral Contraceptives on the Activity of the Hypothalamus-Pituitary-Adrenal Axis
Kirschbaum et al.
Psychosom. Med. 1999;61:154-162.
ABSTRACT | FULL TEXT  

Low-Dose Hydrocortisone for Treatment of Chronic Fatigue Syndrome: A Randomized Controlled Trial
McKenzie et al.
JAMA 1998;280:1061-1066.
ABSTRACT | FULL TEXT  

Increased Evening Activation of the Hypothalamic-Pituitary-Adrenal Axis in Depressed Patients
Young et al.
Arch Gen Psychiatry 1994;51:701-707.
ABSTRACT  

Dissociation Between Pituitary and Adrenal Suppression to Dexamethasone in Depression
Young et al.
Arch Gen Psychiatry 1993;50:395-403.
ABSTRACT  

The Myth of Attention Deficit- Hyperactivity Disorder: Symptoms Resulting from Multiple Causes
Weinberg and Brumback
J Child Neurol 1992;7:431-445.
 

Loss of Glucocorticoid Fast Feedback in Depression
Young et al.
Arch Gen Psychiatry 1991;48:693-699.
ABSTRACT  

{beta}-Lipotropin--{beta}-Endorphin Response to Low-Dose Ovine Corticotropin Releasing Factor in Endogenous Depression: Preliminary Studies
Young et al.
Arch Gen Psychiatry 1990;47:449-457.
ABSTRACT  

Maximizing Diagnostic Information From the Dexamethasone Suppression Test: An Approach to Criterion Selection Using Receiver Operating Characteristic Analysis
Mossman and Somoza
Arch Gen Psychiatry 1989;46:653-660.
ABSTRACT  

Neuroendocrine Response to 5-Hydroxytryptophan in Seasonal Affective Disorder
Jacobsen et al.
Arch Gen Psychiatry 1987;44:1086-1091.
ABSTRACT  

Pituitary and Adrenocortical Responses to the Ovine Corticotropin Releasing Hormone in Depressed Patients and Healthy Volunteers
Amsterdam et al.
Arch Gen Psychiatry 1987;44:775-781.
ABSTRACT  

Neuroendocrine Aspects of Primary Endogenous Depression: I. Cortisol Secretory Dynamics in Patients and Matched Controls
Rubin et al.
Arch Gen Psychiatry 1987;44:328-336.
ABSTRACT  

Enhanced Adrenal Sensitivity to Exogenous Cosyntropin (ACTH {alpha}1-24) Stimulation in Major Depression: Relationship to Dexamethasone Suppression Test Results
Jaeckle et al.
Arch Gen Psychiatry 1987;44:233-240.
ABSTRACT  

Depression and Dexamethasone Suppression Testing in Children and Adolescents
Emslie et al.
J Child Neurol 1987;2:31-37.
ABSTRACT  

CSF Somatostatin and Abnormal Response to Dexamethasone Administration in Schizophrenic and Depressed Patients
Doran et al.
Arch Gen Psychiatry 1986;43:365-369.
ABSTRACT  

{beta}-Endorphin/{beta}-Lipotropin Immunoreactivity in Endogenous Depression: Effect of Dexamethasone
Matthews et al.
Arch Gen Psychiatry 1986;43:374-381.
ABSTRACT  

The Dexamethasone Suppression Test for Diagnosis and Prognosis in Psychiatry: Commentary and Review
Arana et al.
Arch Gen Psychiatry 1985;42:1193-1204.
ABSTRACT  

Cortisol Secretion in Endogenous Depression: I. Basal Plasma Levels
Halbreich et al.
Arch Gen Psychiatry 1985;42:904-908.
ABSTRACT  

Cortisol Secretion in Endogenous Depression: II. Time-Related Functions
Halbreich et al.
Arch Gen Psychiatry 1985;42:909-914.
ABSTRACT  

Opioid Regulation of Hypothalamic-Pituitary-Adrenal Function in Depression
Zis et al.
Arch Gen Psychiatry 1985;42:383-386.
ABSTRACT  

Clinical Applications of Corticotropin-Releasing Factor
CHROUSOS et al.
ANN INTERN MED 1985;102:344-358.
ABSTRACT  

Variability in Cortisol Level Assay Methods
Rubin and Poland
Arch Gen Psychiatry 1984;41:724-725.
ABSTRACT  

Pretreatment DST and Hypothalamic-Pituitary-Adrenocortical Function in Depressed Patients and Comparison Groups: A Multicenter Study
Stokes et al.
Arch Gen Psychiatry 1984;41:257-267.
ABSTRACT  

Circadian Analysis of Plasma Cortisol Levels Before and After Dexamethasone Administration in Depressed Patients
Sherman et al.
Arch Gen Psychiatry 1984;41:271-275.
ABSTRACT  

The Dexamethasone Suppression Test for the Detection, Diagnosis, and Management of Depression
ANN INTERN MED 1984;100:307-308.
ABSTRACT  

Seasonal Affective Disorder: A Description of the Syndrome and Preliminary Findings With Light Therapy
Rosenthal et al.
Arch Gen Psychiatry 1984;41:72-80.
ABSTRACT  

Dexamethasone Suppression Tests in Antidepressant Treatment of Melancholia: The Process of Normalization and Test-Retest Reproducibility
Greden et al.
Arch Gen Psychiatry 1983;40:493-500.
ABSTRACT  

A Neuroendocrine Test Battery in Bipolar Patients and Healthy Subjects
Amsterdam et al.
Arch Gen Psychiatry 1983;40:515-521.
ABSTRACT  

Plasma Immunoreactive {beta}-Endorphin Levels in Depression: Effect of Electroconvulsive Therapy
Alexopoulos et al.
Arch Gen Psychiatry 1983;40:181-183.
ABSTRACT  

Blunted Prolactin Response: A Neuroendocrine Abnormality Manifested by Depressed Patients
Judd et al.
Arch Gen Psychiatry 1982;39:1413-1416.
ABSTRACT  

Hypothalamic-Pituitary-Adrenal Axis Activity and Tricyclic Response in Major Depression
Nelson et al.
Arch Gen Psychiatry 1982;39:1033-1036.
ABSTRACT  

Diagnosis and Neuroanatomical Correlates of Depression in Brain-Damaged Patients: Implications for a Neurology of Depression
Ross and Rush
Arch Gen Psychiatry 1981;38:1344-1354.
ABSTRACT  

Receptor Sensitivity and the Mechanism of Action of Antidepressant Treatment: Implications for the Etiology and Therapy of Depression
Charney et al.
Arch Gen Psychiatry 1981;38:1160-1180.
ABSTRACT  

Diagnosis of Depression in the 1980s
Gold et al.
JAMA 1981;245:1562-1564.
ABSTRACT  

A Specific Laboratory Test for the Diagnosis of Melancholia: Standardization, Validation, and Clinical Utility
Carroll et al.
Arch Gen Psychiatry 1981;38:15-22.
ABSTRACT  

Mood and behavioral effects of physostigmine on humans are accompanied by elevations in plasma beta-endorphin and cortisol
Risch et al.
Science 1980;209:1545-1546.
ABSTRACT  

Hypothalamic-Pituitary-Adrenal Axis Activity in Depressive Illness: Its Relationship to Classification
Schlesser et al.
Arch Gen Psychiatry 1980;37:737-743.
ABSTRACT  

Response to Dexamethasone and Subtype of Depression
Brown and Shuey
Arch Gen Psychiatry 1980;37:747-751.
ABSTRACT  

Dextroamphetamine and Cortisol in Depression: Morning Plasma Cortisol Levels Suppressed
Sachar et al.
Arch Gen Psychiatry 1980;37:755-757.
ABSTRACT  

Cortisol in the CSF of Depressed and Suicidal Patients
Traskman et al.
Arch Gen Psychiatry 1980;37:761-767.
ABSTRACT  

Lithium Prophylaxis of Corticotropin-lnduced Psychosis
Falk et al.
JAMA 1979;241:1011-1012.
ABSTRACT  

Use of Antidepressant Drugs in Schizophrenia
Siris et al.
Arch Gen Psychiatry 1978;35:1368-1377.
ABSTRACT