The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2008-04, Vol.40 (3), p.1175-1180
• Main Authors: Pinborg, Lars H., Arfan, Haroon, Haugbol, Steven, Kyvik, Kirsten Ohm, Hjelmborg, Jacob v. B., Svarer, Claus, Frokjaer, Vibe G., Paulson, Olaf B., Holm, Soren, Knudsen, Gitte M.
• Format: Article
• Language: English
• Subjects: Adult; Age; Analysis of Variance; Behavior; Brain - diagnostic imaging; Brain Chemistry - genetics; Brain research; Charitable foundations; Heritability; Humans; Isotope Labeling; Ketanserin - analogs & derivatives; Ligands; Magnetic Resonance Imaging; Male; Medical imaging; Medical research; Middle Aged; Multivariate analysis; NMR; Nuclear magnetic resonance; Older people; Positron emission tomography; Radionuclide Imaging; Radiopharmaceuticals; Receptor; Receptor, Serotonin, 5-HT2A - genetics; Receptor, Serotonin, 5-HT2A - metabolism; Scanners; Serotonin 2A; Studies; Twins; Twins, Dizygotic; Twins, Monozygotic
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2007.09.019

With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT2A) receptors have been reported to occur in various neuropsychiatric disorders and an association between 5-HT2A receptor gene variants and neuropsychiatric illness susceptibility also exists. In a classical twin design involving 24 healthy male subjects (6 monozygotic twin pairs and 6 dizygotic twin pairs), we examined the relative contribution of genetic and environmental factors to interindividual variability in cortical 5-HT2A receptor binding as measured with [18F]altanserin PET imaging. The intraclass correlation coefficients were 0.67 for dizygotic and 0.87 for monozygotic twin pairs. For comparison, the intraclass correlation coefficient was 0.93 in a group of six male healthy subjects examined twice within two weeks with an identical experimental setup. Multivariate analysis was used to separate the phenotypic variance of individuals into additive genetic (heritability) effect (A), shared (family) environment (C), and non-shared (individual-specific) environment (E). Irrespective of whether a full ACE model or a reduced AE model was used to fit the data, the variance due to non-shared environment was below 10% indicating that the contribution of individual specific environmental factors to 5-HT2A receptor binding is limited.