HPA Axis in Depression and Anxiety

Summary

Principal Investigator: ELIZABETH ANN YOUNG
Affiliation: University of Michigan
Country: USA
Abstract: DESCRIPTION: (Applicant's abstract) This is a Research Scientist Award Application. I have received 15 years of salary support through the RSDA program and have become a leader in the area of HPA axis regulation in depression. Future studies proposed in this application will continue to explore hormonal abnormalities in depression and also in related anxiety disorders, panic disorder and PTSD. Current research indicates that depression is accompanied by abnormalities of the HPA axis, while anxiety disorders, particularly Panic Disorder, is accompanied by abnormalities of the central noradrenergic system, as reflected by a blunted growth hormone response to clonidine. Specific research aims in this proposal are I) to determine if abnormalities of central noradrenergic system are present in both pure depression, pure panic disorder and depression plus panic disorder. We will study a group of well characterized pure depressed, pure panic and mixed panic and depressed patients with the clonidine/growth hormone challenge to determine if all depressed patients manifest abnormalities in clonidine stimulated growth hormone release or if only those with co-morbid panic symptoms manifest this abnormality. 2) To determine if abnormal activation of HPA axis secretion occurs in Panic Disorder patients. We will examine 24 hr urinary cortisol excretion, collected in 8 hrs segments in pure depressed, pure panic and and mixed panic and depressed patients. 3) To evaluate noradrenergic and HPA axis 'reactivity' to two simple challenges in pure depression, depression plus anxiety, panic disorder patients and normal controls. These challenges include orthostatic challenge and the Trier Social Stress Test (TSST). We hypothesize that panic disorder patients and depressed patients with co-morbid anxiety will demonstrate exaggerated catecholamine response to orthostatic challenge i.e increased reactivity. We hypothesize that depressed patients will have altered HPA axis responses to stress response while Panic Disorder patients will have normal HPA axis response to the TSST. 4 ) To determine if the abnormalities in basal HPA axis dysregulation, exaggerated responses to stress and blunted response to clonidine-growth hormone challenge studies occur in the same individuals and if the results of these biological studies support the nosological distinction between Panic Disorder, pure Major Depression and Major Depression with co-morbid Panic Disorder. Finally we will examine whether HPA axis and noradrenergic dysfunction reflect a common factor, degree of impairment, more than a specific mood and anxiety disorder. With regards to PTSD, we will explore whether decreases in urinary free cortisol and increases in urinary catecholamines are present in epidemiological sample of subjects exposed to trauma both with and without PTSD and normal subjects not exposed to trauma who are free of Psychiatric disorders.
Funding Period: 2001-05-01 - 2006-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Modeling cortisol rhythms in a population-based study
    Nalini Ranjit
    Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, MI 48104, USA
    Psychoneuroendocrinology 30:615-24. 2005
  2. ncbi Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression
    Elizabeth A Young
    Department of Psychiatry and Molecular and Behavioral Neurosciences Institute, University of Michigan, MBNI, 205 Zina Pitcher Place, Ann Arbor, MI 48109 0720, and Massachusetts General Hospital, Boston 02114, USA
    Psychoneuroendocrinology 32:843-53. 2007
  3. ncbi Frontal and limbic activation during inhibitory control predicts treatment response in major depressive disorder
    Scott A Langenecker
    Department of Psychiatry, University of Michigan Medical Center, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA
    Biol Psychiatry 62:1272-80. 2007
  4. ncbi Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression
    Elizabeth A Young
    Department of Psychiatry, The University of Michigan, Ann Arbor, MI 48109, USA
    Psychoneuroendocrinology 32:503-7. 2007
  5. ncbi Saliva cortisol and response to dexamethasone in children of depressed parents
    Elizabeth A Young
    Department of Psychiatry, Mental Health Research Institute, University of Michigan, School of Medicine, Ann Arbor, Michigan 48109 0720, USA
    Biol Psychiatry 60:831-6. 2006
  6. ncbi The health of poor women under welfare reform
    George A Kaplan
    Center for Social Epidemiology and Population Health, 1214 S University Ave, Ann Arbor, MI 48104, USA
    Am J Public Health 95:1252-8. 2005
  7. ncbi Material hardship alters the diurnal rhythm of salivary cortisol
    Nalini Ranjit
    Center for Social Epidemiology and Population Health, Department of Epidemiology, School of Public Health, University of Michigan, MI, USA
    Int J Epidemiol 34:1138-43. 2005
  8. ncbi The pattern of growth hormone secretion during the menstrual cycle in normal and depressed women
    Josephine Z Kasa-Vubu
    Department of Pediatrics, Division of Pediatric Endocrinology, University of Michigan, Ann Arbor, Michigan 48019 0718, USA
    Clin Endocrinol (Oxf) 62:656-60. 2005
  9. ncbi Interaction of brain noradrenergic system and the hypothalamic-pituitary-adrenal (HPA) axis in man
    Elizabeth A Young
    Department of Psychiatry, University of Michigan, Ann Arbor, 48109 0720, USA
    Psychoneuroendocrinology 30:807-14. 2005
  10. ncbi Trait negative affect: toward an integrated model of understanding psychological risk for impairment in cardiac autonomic function
    Maria E Bleil
    Department of Psychiatry, University of California San Francisco, 3333 California Street, Suite 465, San Francisco, CA 94143 0848, USA
    Psychosom Med 70:328-37. 2008

Detail Information

Publications10

  1. ncbi Modeling cortisol rhythms in a population-based study
    Nalini Ranjit
    Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, MI 48104, USA
    Psychoneuroendocrinology 30:615-24. 2005
    ..Sharp inflection points for the diurnal profile of cortisol were noted at 30 and 75 min past awakening. Obese women showed a slight tendency to have a less sharply rising and declining response to awakening than non-obese women...
  2. ncbi Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression
    Elizabeth A Young
    Department of Psychiatry and Molecular and Behavioral Neurosciences Institute, University of Michigan, MBNI, 205 Zina Pitcher Place, Ann Arbor, MI 48109 0720, and Massachusetts General Hospital, Boston 02114, USA
    Psychoneuroendocrinology 32:843-53. 2007
    ....
  3. ncbi Frontal and limbic activation during inhibitory control predicts treatment response in major depressive disorder
    Scott A Langenecker
    Department of Psychiatry, University of Michigan Medical Center, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA
    Biol Psychiatry 62:1272-80. 2007
    ..Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD...
  4. ncbi Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression
    Elizabeth A Young
    Department of Psychiatry, The University of Michigan, Ann Arbor, MI 48109, USA
    Psychoneuroendocrinology 32:503-7. 2007
    ..These data suggest that pulsatility and mean ACTH levels are examining different aspects of HPA axis function, and that the types of HPA axis dysregulation in depression may differ between men and women...
  5. ncbi Saliva cortisol and response to dexamethasone in children of depressed parents
    Elizabeth A Young
    Department of Psychiatry, Mental Health Research Institute, University of Michigan, School of Medicine, Ann Arbor, Michigan 48109 0720, USA
    Biol Psychiatry 60:831-6. 2006
    ..However, depression in a parent might also act as a stressor leading to increased activation of neuroendocrine stress circuits. To address this question we examined saliva cortisol in children whose parents have a history of MDD...
  6. ncbi The health of poor women under welfare reform
    George A Kaplan
    Center for Social Epidemiology and Population Health, 1214 S University Ave, Ann Arbor, MI 48104, USA
    Am J Public Health 95:1252-8. 2005
    ..We compared the health of single mothers affected by welfare reform with the health of a nationally representative sample of women to document the prevalence of poor health as single mothers experience the effects of welfare reform...
  7. ncbi Material hardship alters the diurnal rhythm of salivary cortisol
    Nalini Ranjit
    Center for Social Epidemiology and Population Health, Department of Epidemiology, School of Public Health, University of Michigan, MI, USA
    Int J Epidemiol 34:1138-43. 2005
    ..As there is some evidence that both acute and chronic stress raise cortisol levels, and material hardship is a stressor, we examined the relationship of chronic material hardship with salivary cortisol levels over the day...
  8. ncbi The pattern of growth hormone secretion during the menstrual cycle in normal and depressed women
    Josephine Z Kasa-Vubu
    Department of Pediatrics, Division of Pediatric Endocrinology, University of Michigan, Ann Arbor, Michigan 48019 0718, USA
    Clin Endocrinol (Oxf) 62:656-60. 2005
    ..The aim of this study was to investigate changes of growth hormone (GH) secretion during the menstrual cycle in normal and depressed women...
  9. ncbi Interaction of brain noradrenergic system and the hypothalamic-pituitary-adrenal (HPA) axis in man
    Elizabeth A Young
    Department of Psychiatry, University of Michigan, Ann Arbor, 48109 0720, USA
    Psychoneuroendocrinology 30:807-14. 2005
    ..This relationship is less well characterized in humans and little is known about the influence of psychiatric disorders, which disturb one of these systems, on this relationship...
  10. ncbi Trait negative affect: toward an integrated model of understanding psychological risk for impairment in cardiac autonomic function
    Maria E Bleil
    Department of Psychiatry, University of California San Francisco, 3333 California Street, Suite 465, San Francisco, CA 94143 0848, USA
    Psychosom Med 70:328-37. 2008
    ..g., autonomic nervous system [ANS] dysfunction), the degree to which a general tendency to experience negative emotions may account for these relations is not known...