One contribution of 11 to a Theme Issue 'The neurobiology of depression-revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies'. ography, 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 (BP F ) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP F 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 BP F in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT 1A BP F 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 [ 11 C]CUMI-101 agonist tracer.