Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Objective: Lower serotonin transporter (5-HTT) binding (BP_P = f_PB_avail/K_D) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD). Methods: 5-HTT binding was quantified using positron emission tomography (PET) with [¹¹C]McN5652 in 19 currently depressed subjects with MDD and 41 healthy controls. Depressed subjects received open, naturalistic antidepressant treatment. Remission status was determined one year after PET scan and treatment initiation. Results: Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p = 0.057). Limitations: The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome. Conclusions: Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.