Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: A positron emission tomography study
Open accessAbstract
Background Major depressive disorder is associated with raised peripheral inflammatory markers. Mounting evidence also suggests that inflammation is involved in suicidal behavior. However, the involvement of inflammation in the brains of individuals with depression, and its association with suicidal ideation, needs further clarification. Translocator protein (TSPO), which is upregulated in activated glia (predominantly microglia), can be measured as an indication of neuroinflammation in vivo using positron emission tomography and TSPO-specific radioligands.Methods We used [11 C](R)-PK11195 positron emission tomography to compare TSPO availability in the anterior cingulate cortex (ACC), prefrontal cortex, and insula between 14 medication-free patients in a major depressive episode of at least moderate severity and 13 matched healthy control subjects. In a post hoc analysis, we also compared TSPO availability between patients with and without suicidal thoughts.Results Multivariate analysis of variance indicated significantly higher TSPO in patients compared with control subjects (p = .005). The elevation was of large effect size and significant in the ACC (p = .022, Cohen's d = 0.95), with smaller nonsignificant elevations in the prefrontal cortex (p = .342, Cohen's d = 0.38) and insula (p = .466, Cohen's d = 0.29). TSPO was not elevated in patients without suicidal thinking but was significantly increased in those with suicidal thoughts compared with those without, most robustly in the ACC (p = .008) and insula (p = .023).Conclusions We confirm evidence for increased TSPO availability, suggestive of predominantly microglial activation, in the ACC during a moderate to severe major depressive episode. Our findings provide further incentive for evaluating anti-inflammatory therapies in major depressive disorder.
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Recent imaging studies report greater neuroinflammation in the hippocampus and medial prefrontal cortex of depressed people than in healthy controls.
“recent imaging studies in depressed individuals have reported enhanced neuroinflammation in the hippocampus and mPFC compared to HCs (93,94).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [94]
Activated microglia and brain TSPO are linked to suicide risk independently of the presence of psychiatric disorders.
“Activated microglia (208, 209), the primary immune response cells in the brain, and brain translocator protein (TSPO) found in mitochondria of activated glial cells (210) are linked to suicide risk, independently of the presence of psychiatric disorders.”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [210]
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- Authors
- Holmes, S. E., Hinz, R., Conen, S., Gregory, C. J., Matthews, J. C., Anton-Rodriguez, J. M., Gerhard, A., & Talbot, P. S.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Greater Manchester Mental Health NHS Foundation Trust (GB)
- Corresponding author
- Talbot, Peter S.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 83
- Issue
- 1
- Pages
- 61-69
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2743887053
- Cited by
- 346
- References
- 90
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 37 · 2023: 33 · 2022: 34 · 2021: 68 · 2020: 50 · 2019: 42 · 2018: 27 · 2017: 5
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- Ministère des relations internationales et de la Francophonie
- National Institute for Health and Care Research (FP7/2007–2013, ACF-2012-06-008)
- European Commission (2007–2013, FP7 2007-2013, FP7/2007, 278850)
- Engineering and Physical Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- translocator protein (TSPO), TSPO, major depressive disorder, neuroinflammation, microglial activation, anterior cingulate cortex, suicidal ideation, prefrontal cortex, insula, anti-inflammatory therapy
- MeSH terms
- Adult, Brain Mapping, Carbon Radioisotopes, Major Depressive Disorder, Female, Gyrus Cinguli, Humans, Inflammation, Isoquinolines, Male, Severity of Illness Index, Multivariate Analysis, Prefrontal Cortex, Microglia, Receptors, GABA, Radiopharmaceuticals, Positron-Emission Tomography, Suicidal Ideation
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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.
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