THE PSYCHOBIOLOGY OF CORTICOTROPIN-RELEASING FACTOR

Project: Research project

Description

Since elucidation of its structure in 1981, corticotropin-releasing
factor (CRF), a neuropeptide comprised of 41 amino acids, has
been shown to function as a hypothalamic releasing hormone by
regulating the secretion of corticotropin (ACTH) and other pro-
opiomelanocortin-related peptides from the anterior pituitary.
The heterogeneous distribution of CRF and CRF receptors in
hypothalamic and extrahypothalamic regions of the mammalian
CNS, and its electrophysiological and behavioral effects, all are
concordant with an extra-endocrine role for this peptide in
higher brain centers. The present proposal seeks to utilize
preclinical and clinical paradigms to provide further evidence for
a role for CRF as a neurotransmitter in the CNS, and
furthermore, to investigate the hypothesis that CRF is
hypersecreted in patients with major depression. Towards the
former goal, we shall elucidate CRF-containing neural circuits in
the rat CNS by a combination of chemical lesioning techniques
and use of a sensitive and specific radioimmunoassay for the
peptide, determine what neurotransmitters/neuromodulators
regulate CRF release, determine the subcellular distribution of
CRF, determine whether cyclic nucleotides mediate CRF
responses in the CNS and finally, determine the role of CRF
neurons in responses to acute and chronic stress. Towards the
latter goal, we shall attempt to confirm and extend our previous
findings that cerebrospinal fluid (CSF) concentrations of CRF
are elevated in patients with major depression by studying a
large population of well-characterized, drug-free
neuropsychiatric patients. The specificity of this finding will be
studied by measurement of CSF CRF, not only in patients with
major depression, but also in schizophrenic and demented
patients, as well as patients with Huntington's chorea and
multiple sclerosis. We shall determine whether the elevation in
CSF CRF-L1 is state-dependent by: 1) determining whether
treatment with electroconvulsive therapy (ECT) produces a
significant reduction in CSF CRF-L1, and, 2) determining
whether treatment with tricyclic antidepressants in multiple
sclerosis patients with depression results in a reduction in CSF
CRF-L1. Finally, the specificity of the blunted ACTH response
to intravenously (IV)-administered CRF in depressed patients will
be explored. We shall study patients not only with major
depression, but also those with diagnoses of schizophrenia, post-
traumatic stress disorder and panic disorder, resulting in novel
information on the role of CRF in affective disorders.
StatusFinished
Effective start/end date1/1/877/31/10

Funding

  • National Institutes of Health: $380,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $288,501.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $380,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $381,458.00
  • National Institutes of Health
  • National Institutes of Health: $380,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $213,965.00

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Corticotropin-Releasing Hormone
Depression
Corticotropin-Releasing Hormone Receptors
Adrenocorticotropic Hormone
Neurons
Research Personnel
Antidepressive Agents
Neurotransmitter Agents
Brain
Maternal Deprivation
Locus Coeruleus
Animal Models
Signal Transduction
Urocortins
Child Abuse
Suicide
Organized Financing
Pituitary Hormone-Releasing Hormones
Messenger RNA
Pro-Opiomelanocortin

ASJC

  • Medicine(all)