Serotonin-1A receptor imaging in recurrent depression: replication and literature review

Abstract Introduction Serotonin-1A receptor (5-HT1A R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT1A R agonists in vivo and to 5-HT1A R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT1A R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-11 C]WAY-100635, and we have demonstrated reduced 5-HT1A R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders ( n =12) versus controls ( n =8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999;46(10):1375–87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods Using PET and [carbonyl-11 C]WAY-100635, 5-HT1A R BP was assessed in 16 depressed subjects and 8 healthy controls. Results Mean 5-HT1A R BP was reduced by 26% in the MTC ( P < .005) and by 43% in the raphe ( P < .001) in depressives versus controls. Conclusions These data replicate our original findings, which showed that BP was reduced by 27% in the MTC ( P < .025) and by 42% in the raphe ( P < .02) in depression. The magnitudes of these reductions in 5-HT1A R binding were similar to those found postmortem in 5-HT1A R mRNA concentrations in the hippocampus in MDD [López JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547–73] and in 5-HT1A R-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001;25(6):892–903]. There exists disagreement within the literature, however, regarding the presence and direction of 5-HT1A R-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location