TY - JOUR
T1 - Effect of Antidepressant Treatment on 5-HT4 Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder
AU - Dam, Vibeke H.
AU - Köhler-Forsberg, Kristin
AU - Ozenne, Brice
AU - Larsen, Søren V.
AU - Ip, Cheng Teng
AU - Jorgensen, Anders
AU - Stenbæk, Dea S.
AU - Madsen, Jacob
AU - Svarer, Claus
AU - Jørgensen, Martin B.
AU - Knudsen, Gitte M.
AU - Frokjaer, Vibe G.
N1 - Publisher Copyright:
© 2024 Society of Biological Psychiatry
PY - 2025
Y1 - 2025
N2 - Background: Brain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT4R 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-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R 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-HT4R 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-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R 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-HT4R levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HT4R 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.
AB - Background: Brain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HT4R 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-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R 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-HT4R 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-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R 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-HT4R levels, which is consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels were downregulated after selective serotonin reuptake inhibitors, the more verbal memory improved, highlighting the potential importance of 5-HT4R 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.
KW - Antidepressant treatment
KW - Cognition
KW - Depression
KW - Positron emission tomography (PET)
KW - Serotonin 4 receptor
KW - Verbal memory
U2 - 10.1016/j.biopsych.2024.08.009
DO - 10.1016/j.biopsych.2024.08.009
M3 - Journal article
C2 - 39181386
AN - SCOPUS:85207716388
VL - 97
SP - 261
EP - 268
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 3
ER -