Molecular imaging of the serotonin transporter availability and occupancy by antidepressant treatment in late-life depression.
Affect
/ drug effects
Aged
Aged, 80 and over
Aging
Antidepressive Agents
/ therapeutic use
Brain
/ metabolism
Citalopram
/ therapeutic use
Depressive Disorder, Major
/ drug therapy
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Molecular Imaging
Serotonin Plasma Membrane Transport Proteins
/ metabolism
Selective Serotonin Reuptake Inhibitors
/ therapeutic use
Sertraline
/ therapeutic use
Aging
Citalopram
Late-life depression
Positron emission tomography (PET)
Selective serotonin reuptake inhibitors
Serotonin transporter
Sertraline
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
15 08 2021
15 08 2021
Historique:
received:
07
09
2020
revised:
04
12
2020
accepted:
30
12
2020
pubmed:
16
1
2021
medline:
29
12
2021
entrez:
15
1
2021
Statut:
ppublish
Résumé
Patients with late-life depression (LLD) have a more variable response to pharmacotherapy relative to patients with mid-life depression. Degeneration of the serotonergic system and lower occupancy of the initial target for antidepressant medications, the serotonin transporter (5-HTT), may contribute to variability in treatment response. The focus of this study was to test the hypotheses that lower cortical and limbic serotonin transporter (5-HTT) availability in LLD patients relative to controls and less 5-HTT occupancy by antidepressant medications would be associated with less improvement in mood and cognition with treatment in LLD patients. Twenty LLD patients meeting DSM-IV criteria for a current major depressive episode and 20 non-depressed controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes and high-resolution positron emission tomography (PET) scanning to measure 5-HTT before and after 10-12 weeks of treatment with Citalopram or Sertraline (patients only). Prior to treatment, 5-HTT was lower in LLD patients relative to controls in mainly temporal cortical and limbic (amygdala and hippocampus) regions. Gray matter volumes were not significantly different between groups. 5-HTT occupancy was detected throughout cortical, striatal, thalamic and limbic regions. The magnitude of regional 5-HTT occupancy by antidepressants was 70% or greater across cortical and sub-cortical regions, consistent with the magnitude of 5-HTT occupancy observed in mid-life depressed patients. Greater regional 5-HTT occupancy correlated with greater improvement in depressive symptoms and visual-spatial memory performance. These data support the hypothesis that serotonin degeneration and variability in 5-HTT occupancy may contribute to heterogeneity in treatment response in LLD patients.
Identifiants
pubmed: 33450276
pii: S0028-3908(21)00001-0
doi: 10.1016/j.neuropharm.2021.108447
pmc: PMC8716112
mid: NIHMS1713160
pii:
doi:
Substances chimiques
Antidepressive Agents
0
Serotonin Plasma Membrane Transport Proteins
0
Serotonin Uptake Inhibitors
0
Citalopram
0DHU5B8D6V
Sertraline
QUC7NX6WMB
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108447Subventions
Organisme : NIMH NIH HHS
ID : R01 MH064823
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041633
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059390
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG038893
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH086881
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003098
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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