Imaging the serotonin 1A receptor using[¹¹C]WAY100635 in healthy controls and major depression

As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the _1A receptor (5-HT_1A) has been implicated in depression and suicide. Using the [carbonyl-¹¹C]WAY100635 ([¹¹C]WAY) ligand and positron emission tomography, we have studied the 5-HT_1A receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT_1A binding potential (BPF) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BPF in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BPF in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT_1A BPF may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT_1A imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [¹¹C]CUMI-101 agonist tracer.