Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAAReceptor Subunits in Frontal Cortical Brain Region
Open accessAbstract
Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH 1, and CRH 2 receptors, as well as various GABA A receptor subunits (α1, α2, α3, α4, α5, δ, and γ2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH 1, but not CRH 2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the α1, α3, α4, and δ receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABA A receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABA A receptor subunit changes, or the disturbed coordination between these GABA A receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.
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Dysregulated glutamate and GABA gene expression in the prefrontal cortex suggests an imbalance between excitatory and inhibitory neurotransmission.
“Dysregulated glutamate and GABA gene expression in the PFC suggest an imbalance between excitatory and inhibitory neurotransmission (31).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [31]
The Discussion (page not available in our copy) reports dysregulated GABA_A receptor-subunit expression in frontal cortical regions and suggests that reduced inhibitory tone is possible, while calling its consequences speculative. The paper examines CRH and GABA-related expression, not dysregulated glutamate gene expression, so it does not support that part of the attributed claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAbnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have been implicated in suicide.
“Abnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have also been implicated in suicide.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [31]
The Introduction (page not available in our copy) discusses GABA-related findings in depressed suicide victims, and the Discussion links altered GABA_A receptor-subunit expression with suicide. The cited paper does not substantiate the sentence’s additional claims about dopaminergic, glutamatergic, or endocannabinoid abnormalities in suicide. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCRF1 receptors/binding sites are reduced in postmortem brains from suicide victims, many of whom had a history of depression.
“CRF1 receptors/binding sites are reduced in postmortem brains from suicide victims, many of whom showed a history of depression.52,53”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [52]
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- Shiah IS, Yatham LN (1998) GABA function in mood disorders: an update and critical review. Life Sci 63:1289 -1303.
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“Dysregulated glutamate and GABA gene expression in the PFC suggest an imbalance between excitatory and inhibitory neurotransmission (31).”
- Authors
- Merali, Z., Du, L., Hrdina, P., Palkovits, M., Faludi, G., Poulter, M. O., & Anisman, H.
- Affiliations
- University of Ottawa (CA)
- Institute of Mental Health Research (CA)
- Carleton University (CA)
- Corresponding author
- Anisman, Hymie
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-02-11
- Volume
- 24
- Issue
- 6
- Pages
- 1478-1485
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730322
- OpenAlex
- W2159750050
- Cited by
- 400
- References
- 0
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 14 · 2023: 12 · 2022: 6 · 2021: 19 · 2020: 11 · 2019: 22 · 2018: 12 · 2017: 19 · 2016: 20 · 2015: 12 · 2014: 30 · 2013: 16 · 2012: 34
- FWCI
- 20.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carleton University's Institutional Repository (MacOdrum Library, Carleton University) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- suicide, depression, corticotropin-releasing factor, CRH receptors, GABAA receptor subunits, frontal cortex, prefrontal cortex, gene expression, GABA, gene expression regulation, suicide victims
- MeSH terms
- CRF Receptor, Type 1, Brain, Carrier Proteins, Corticotropin-Releasing Hormone, Female, Frontal Lobe, Humans, Male, Middle Aged, Receptors, GABA-A, RNA, Messenger, Suicide, Receptors, Corticotropin-Releasing Hormone, Protein Subunits, White People
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