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Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder
Dam, Vibeke H.1,2; Köhler-Forsberg, Kristin1,2,3; Ozenne, Brice1,4; Larsen, Søren V.1,2; Ip, Cheng Teng1,2,5; Jorgensen, Anders2,3; Stenbæk, Dea S.1,6; Madsen, Jacob7; Svarer, Claus1; Jørgensen, Martin B.1,2,3; Knudsen, Gitte M.1,2; Frokjaer, Vibe G.1,2,3
2025-02-01
Source PublicationBiological Psychiatry
ISSN0006-3223
Volume97Issue:3Pages:261-268
AbstractBackground: Brain serotonin 4 receptor (5-HTR) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HTR levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment. Methods: Ninety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HTR binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HTR binding was assessed for its ability to predict treatment outcome at weeks 4, 8, or 12. In 40 patients who were rescanned 8 weeks posttreatment, change in cerebral 5-HTR binding was correlated with change in verbal memory and with change in depressive symptoms, as evaluated by the 6-item Hamilton Depression Rating Scale. Results: After 8 weeks of serotonergic intervention, neostriatal 5-HTR binding was reduced by 9%. Global change in 5-HTR binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HTR binding did not predict clinical recovery status at week 8 and was not associated with change in the 6-item Hamilton Depression Rating Scale scores. Conclusions: In patients with moderate to severe MDD, treatment with selective serotonin reuptake inhibitors downregulated neostriatal 5-HTR levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HTR levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HTR as a treatment target in MDD. The findings offer insights into mechanisms that underlie antidepressant effects and point to new directions for precision medicine treatments for MDD.
KeywordAntidepressant treatment Cognition Depression Positron emission tomography (PET) Serotonin 4 receptor Verbal memory
DOI10.1016/j.biopsych.2024.08.009
URLView the original
Language英語English
Scopus ID2-s2.0-85207716388
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
2.Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
3.Psychiatric Center Copenhagen, Copenhagen, Denmark
4.Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
5.Center for Cognitive and Brain Sciences, University of Macau, Taipa, Macau SAR, China
6.Department of Psychology, University of Copenhagen, Copenhagen, Denmark
7.Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Recommended Citation
GB/T 7714
Dam, Vibeke H.,Köhler-Forsberg, Kristin,Ozenne, Brice,et al. Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder[J]. Biological Psychiatry, 2025, 97(3), 261-268.
APA Dam, Vibeke H.., Köhler-Forsberg, Kristin., Ozenne, Brice., Larsen, Søren V.., Ip, Cheng Teng., Jorgensen, Anders., Stenbæk, Dea S.., Madsen, Jacob., Svarer, Claus., Jørgensen, Martin B.., Knudsen, Gitte M.., & Frokjaer, Vibe G. (2025). Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder. Biological Psychiatry, 97(3), 261-268.
MLA Dam, Vibeke H.,et al."Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder".Biological Psychiatry 97.3(2025):261-268.
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