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Cited by 137Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression

Zhu, Meng-Yang, Klimek, Violetta, Dilley, Ginny E, Haycock, John W, Stockmeier, Craig, Overholser, James C, Meltzer, Herbert Y, Ordway, Gregory A·1999·Biological Psychiatry
DOI 10.1016/s0006-3223(99)00135-3
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Abstract

Background Levels of tyrosine hydroxylase (TH) are regulated in the noradrenergic locus coeruleus (LC) in response to changes in the activity of LC neurons and in response to changes in brain levels of norepinephrine. To study the potential role of central noradrenergic neurons in the pathobiology of major depression, TH protein was measured in the LC from postmortem brains of 13 subjects with a diagnosis of major depression and 13 age-matched control subjects having no Axis I psychiatric diagnosis. Most of the major depressive subjects died as a result of suicide.Methods Protein from sections cut through multiple rostro-caudal levels of LC was transferred to Immobilon-P membrane, immunoblotted for TH, and quantified autoradiographically.Results The distribution of TH-immunoreactivity (TH-ir) along the rostro-caudal axis of the LC was uneven and was paralleled by a similar uneven distribution of neuromelanin-containing cells in both major depressive and psychiatrically normal control subjects. Amounts of TH-ir in the rostral, middle and caudal levels of the LC from major depressive subjects were significantly higher than that of matched control subjects. There were no significant differences in the number of noradrenergic cells at any particular level of the LC comparing major depressive subjects to control subjects.Conclusions Elevated expression of TH in the LC in major depression implies a premortem overactivity of these neurons, or a deficiency of the cognate transmitter, norepinephrine.

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  • Human functional imaging and postmortem tissue studies have identified abnormalities in several brain regions, including nuclei within the brain's reward pathway, in major depressive disorder.

    “human functional imaging and postmortem tissue studies have identified abnormalities in several brain regions [2–6] including nuclei within the brain’s reward pathway.”

    From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [5]

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Authors
Zhu, M.-Y., Klimek, V., Dilley, G. E., Haycock, J. W., Stockmeier, C., Overholser, J. C., Meltzer, H. Y., & Ordway, G. A.
Affiliations
  • University of Mississippi Medical Center (US)
  • Case Western Reserve University (US)
  • Louisiana State University (US)
Corresponding author
Ordway, Gregory A
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
1999-11
Volume
46
Issue
9
Pages
1275-1286
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/s0006-3223(99)00135-3
OpenAlex
W2001775440
Cited by
137
References
77
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 8 · 2012: 7
FWCI
3.91
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (NIMH 46692, NIMH 45488, R01MH045488, R01MH046692)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
tyrosine hydroxylase, locus coeruleus, major depressive disorder, noradrenergic neurons, norepinephrine, neuromelanin, suicide, postmortem brain
MeSH terms
Adult, Aged, Aged, 80 and over, Autoradiography, Major Depressive Disorder, Female, Humans, Locus Coeruleus, Male, Middle Aged, Neurons, Suicide, Tyrosine 3-Monooxygenase, Immunoblotting, Blotting, Western, Case-Control Studies

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