Impact of COMT genotype on serotonin-1A receptor binding investigated with PET.

Abstract

Alterations of the inhibitory serotonin-1A receptor (5-HT1A) constitute a solid finding in neuropsychiatric research, particularly in the field of mood and anxiety disorders. Manifold factors influencing the density of this receptor have been identified, e.g., steroid hormones, sunlight exposure and genetic variants of serotonin-related genes. Given the close interactions between serotonergic and dopaminergic neurotransmission, we investigated whether a common single-nucleotide-polymorphism of the catechol-O-methyltransferase (COMT) gene (VAL158MET or rs4680) coding for a key enzyme of the dopamine network that is associated with the pathogenesis of mood disorders and antidepressant treatment response, directly affects 5-HT1A receptor binding potential. Fifty-two healthy individuals (38 female, mean age ± standard deviation = 40.48 ± 14.87) were measured via positron emission tomography using the radioligand [carbonyl-(11)C]WAY-100635. Genotyping for rs4680 was performed using DNA isolated from whole blood with the MassARRAY platform of the software SEQUENOM(®). Whole brain voxel-wise ANOVA resulted in a main effect of genotype on 5-HT1A binding. Compared to A carriers (AA + AG) of rs4680, homozygote G subjects showed higher 5-HT1A binding potential in the posterior cingulate cortex (F (2,49) = 17.7, p = 0.05, FWE corrected), the orbitofrontal cortex, the anterior cingulate cortex, the insula, the amygdala and the hippocampus (voxel-level: p < 0.01 uncorrected, t > 2.4; cluster-level: p < 0.05 FWE corrected). In light of the frequently reported alterations of 5-HT1A binding in anxiety and mood disorders, this study proposes a potential implication of the COMT genotype, more specifically the VAL158MET polymorphism, via modulation of the serotonergic neurotransmission.

• Authors: Pia Baldinger, Andreas Hahn, Markus Mitterhauser, Georg S Kranz, Marion Friedl, Wolfgang Wadsak, Christoph Kraus, Johanna Ungersböck, Annette Hartmann, Ina Giegling, Dan Rujescu, Siegfried Kasper, Rupert Lanzenberger
• Journal: Brain structure & function (Brain Struct Funct) Vol. 219 Issue 6 Pg. 2017-28 (Nov 2014) ISSN: 1863-2661 [Electronic] Germany
• PMID: 23928748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Serotonin, 5-HT1A
• COMT protein, human
• Catechol O-Methyltransferase

Topics

• Adult
• Brain (diagnostic imaging, metabolism)
• Catechol O-Methyltransferase (genetics, metabolism)
• Female
• Genotype
• Humans
• Male
• Polymorphism, Single Nucleotide
• Positron-Emission Tomography
• Protein Binding
• Receptor, Serotonin, 5-HT1A (metabolism)