Meta-analysis of molecular imaging of serotonin transporters in major depression

Gryglewski, Gregor; Lanzenberger, Rupert; Kranz, Georg S; Cumming, Paul

doi:10.1038/jcbfm.2014.82

Cited by 236Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionTryptophan and brain disorders

Meta-analysis of molecular imaging of serotonin transporters in major depression

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Gryglewski, Gregor, Lanzenberger, Rupert, Kranz, Georg S, Cumming, Paul·2014·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/jcbfm.2014.82PMC PMC4083395

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Abstract

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 did not find significant changes in serotonin transporter binding or availability in the hippocampus and medial prefrontal cortex in major depressive disorder.
“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]
Human imaging findings on serotonin dysregulation in major depressive disorder are more inconsistent than animal findings.
“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]
MDD is associated with a significant reduction of the 5-HTT in the midbrain and striatum.
“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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Effect of repeated administration of antidepressants on serotonin uptake sites in limbic and neocortical structures of rat brain determined by quantitative autoradiography.
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Unaltered number of brain serotonin uptake sites in suicide victims
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Serotonergic Neuron Stimulation Modulates Thalamocortical Glucose Use in the Conscious Rat
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[17]Hedges L Olkin I (1 st edn) Statistical Methods for Meta-Analysis. Academic Press: San Diego, CA, USA 1985.

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Bridging psychology and genetics using large-scale spatial analysis of neuroimaging and neurogenetic dataPreprint
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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
ORCID: Gryglewski, Gregor
Lanzenberger, Rupert
Kranz, Georg S
Cumming, Paul
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
DOI: 10.1038/jcbfm.2014.82
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: cc-by-nc-sa
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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 › 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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Meta-analysis of molecular imaging of serotonin transporters in major depression

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