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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]
In the citing paper
“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
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