Reduced somatostatin in subgenual anterior cingulate cortex in major depression
Open accessAbstract
Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative Western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=-0.357, p=0.005) but not MDD (R=-0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches to the high female vulnerability to develop MDD.
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Cortical GABAergic disinhibition in depressive disorders co-occurs with increases in glutamatergic gene expression in the default mode network (DMN).
“Specifically, cortical GABAergic disinhibition in depressive disorders co-occurs with increases in glutamatergic gene expression in the DMN [24,26,27,28,29,30,31,32].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [31]
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- Authors
- Tripp, A., Kota, R. S., Lewis, D. A., & Sibille, E.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Sibille, Etienne
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 42
- Issue
- 1
- Pages
- 116-124
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC3039077
- OpenAlex
- W2007197177
- Cited by
- 190
- References
- 54
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 16 · 2023: 16 · 2022: 14 · 2021: 25 · 2020: 13 · 2019: 22 · 2018: 10 · 2017: 7 · 2016: 12 · 2015: 13 · 2014: 8 · 2013: 9 · 2012: 4
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Mental Health (P50MH084053, MH084060, MH084053, MH 45156, MH077159, R01MH077159, P50MH045156, K02MH084060)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- somatostatin, subgenual anterior cingulate cortex, major depressive disorder, sex differences, GABAergic neurons, postmortem brain, age-related decline, depression pathophysiology
- MeSH terms
- Adolescent, Adult, Aged, Depressive Disorder, Major, Major Depressive Disorder, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Neural Pathways, Protein Precursors, Somatostatin, Cohort Studies, Down-Regulation, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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