Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects
Abstract
Research evidence that corticotropin-releasing factor (CRF) plays a role in the pathophysiology of major depressive disorder (MDD) has accumulated over the past 20 years. The elevation of lumbar cerebrospinal fluid (CSF) concentrations of CRF decreased responsiveness of pituitary CRF receptors to challenge with synthetic CRF, and increased levels of serum cortisol in MDD subjects support the hypothesis that CRF is chronically hypersecreted in at least the endocrine circuits of the hypothalamic-pituitary-adrenal (HPA) axis and may also involve other CRF brain circuits mediating emotional responses and/or arousal. One such circuit includes the excitatory CRF input to the locus coeruleus (LC), the major source of norepinephrine in the brain. Furthermore, there are now reports of decreased levels of CRF in lumbar CSF from MDD patients after symptom relief from chronic treatment with antidepressant drugs or electroconvulsive therapy. Whether this normalization reflects therapeutic effects on both endocrine- and limbic-associated CRF circuits has not yet been effectively addressed. In this brief report, we describe increased concentrations of CRF-like immunoreactivity in micropunches of post-mortem LC from subjects with MDD symptoms as established by retrospective psychiatric diagnosis compared to nondepressed subjects matched for age and sex.
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CRF is increased in the locus coeruleus of patients with depression, suggesting that this mechanism may be central to a chronic stress response in humans as well.
“Interestingly, CRF is increased in the locus coeruleus of patients with depression88, suggesting that this mechanism may be central to a chronic stress response in humans as well.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [88]
Higher levels of CRF and CRF-expressing neurons are present in postmortem samples from depressed compared with nondepressed individuals.
“There are higher levels of both CRF and CRF-expressing neurons in postmortems samples from depressed compared with nondepressed individuals.49-51”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [50]
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- Authors
- Bissette, G., Klimek, V., Pan, J., Stockmeier, C., & Ordway, G.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- Bissette, Garth
- Venue
- Neuropsychopharmacology
- Published
- 2003-03-12
- Volume
- 28
- Issue
- 7
- Pages
- 1328-1335
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2323040745
- Cited by
- 136
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 7 · 2012: 6
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (MH-45488, MH 46692, R01MH045488, R01MH046692)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- corticotropin-releasing factor, locus coeruleus, major depressive disorder, postmortem brain, norepinephrine, hypothalamic-pituitary-adrenal axis, antidepressant treatment, electroconvulsive therapy, depression pathophysiology
- MeSH terms
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Corticotropin-Releasing Hormone, Depression, Female, Humans, Locus Coeruleus, Male, Middle Aged, Radioimmunoassay, Case-Control Studies
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