Effect of Antidepressant Treatment on 5-HT Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder.

BACKGROUND

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.