TY - JOUR

T1 - The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

AU - Pinborg, Lars H

AU - Arfan, Haroon

AU - Haugbol, Steven

AU - Kyvik, Kirsten Ohm

AU - Hjelmborg, Jacob v. B.

AU - Svarer, Claus

AU - Frokjaer, Vibe G

AU - Paulson, Olaf B

AU - Holm, Soren

AU - Knudsen, Gitte M

PY - 2007

Y1 - 2007

N2 - 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-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between 5-HT(2A) 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-HT(2A) receptor binding as measured with [(18)F]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-HT(2A) receptor binding is limited.

AB - 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-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between 5-HT(2A) 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-HT(2A) receptor binding as measured with [(18)F]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-HT(2A) receptor binding is limited.

KW - Adult

KW - Analysis of Variance

KW - Brain

KW - Brain Chemistry

KW - Humans

KW - Isotope Labeling

KW - Ketanserin

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Radiopharmaceuticals

KW - Receptor, Serotonin, 5-HT2A

KW - Twins, Dizygotic

KW - Twins, Monozygotic

U2 - 10.1016/j.neuroimage.2007.09.019

DO - 10.1016/j.neuroimage.2007.09.019

M3 - Journal article

C2 - 18291676

VL - 40

SP - 1175

EP - 1180

JO - NeuroImage

JF - NeuroImage

SN - 1053-8119

IS - 3

ER -