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Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression
Open accessAbstract
The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g = −0.49; 95% CI: (−0.84, −0.14)) and amygdala (Hedges' g = −0.50; 95% CI: (−0.78, −0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g = −0.24, striatum: g = −0.32, and brainstem g = −0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations ( P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala ( P = 0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ˜10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.
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“two recent meta-analyses failed to find significant alterations in serotonin transporter binding/availability in the hippocampus and mPFC in MDD (118,119).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [118]
In the citing paper
“human imaging findings in MDD have been more mixed (117–119).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [118]
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“A recent meta-analysis reported that MDD is associated with a significant reduction of the 5-HTT in the midbrain and striatum (Gryglewski et al., 2014).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Gryglewski et al., 2014
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Metadata
- Authors
- Gryglewski, G., Lanzenberger, R., Kranz, G. S., & Cumming, P.
- Affiliations
- Medical University of Vienna (AT)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Lanzenberger, Rupert
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2014-05-07
- Volume
- 34
- Issue
- 7
- Pages
- 1096-1103
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC4083395
- OpenAlex
- W2059391693
- Cited by
- 227
- References
- 89
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 79 · 2023: 19 · 2022: 11 · 2021: 11 · 2020: 14 · 2019: 11 · 2018: 18 · 2017: 15 · 2016: 14 · 2015: 11 · 2014: 6
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
- OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, cc-by-nc-sa)
- Funders
- Austrian Science Fund (P22981)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- serotonin transporter, major depressive disorder, molecular imaging, positron emission tomography, single photon emission computed tomography, amygdala, midbrain, striatum, age effects, depression severity, serotonergic neurotransmission
- MeSH terms
- Brain, Major Depressive Disorder, Humans, Serotonin, Tomography, Emission-Computed, Single-Photon, Positron-Emission Tomography, Serotonin Plasma Membrane Transport Proteins
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.
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