Abstract
Background:
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.
Methods:
We conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT1A BPND.
Results:
No significant differences of 5-HTT nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status.
Conclusion:
In line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT1A receptors in human subjects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Amino Acid Substitution
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Aniline Compounds / pharmacology
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Brain / diagnostic imaging
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Brain / drug effects
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Brain / metabolism
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Brain / pathology
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Brain-Derived Neurotrophic Factor / genetics*
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Brain-Derived Neurotrophic Factor / metabolism
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Case-Control Studies
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Depressive Disorder / diagnostic imaging
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Depressive Disorder / genetics*
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Depressive Disorder / metabolism
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Depressive Disorder / pathology
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Female
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Gene Expression
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Genotype
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Humans
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Male
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Middle Aged
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Piperazines / pharmacology
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Polymorphism, Single Nucleotide*
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Positron-Emission Tomography
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Protein Binding
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Pyridines / pharmacology
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Radiopharmaceuticals / pharmacology
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Receptor, Serotonin, 5-HT1A / genetics*
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Receptor, Serotonin, 5-HT1A / metabolism
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Serotonin / metabolism*
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Serotonin Antagonists / pharmacology
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Serotonin Plasma Membrane Transport Proteins / genetics*
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Sulfides / pharmacology
Substances
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3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile
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Aniline Compounds
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Brain-Derived Neurotrophic Factor
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Piperazines
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Pyridines
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Radiopharmaceuticals
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Serotonin Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Sulfides
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Receptor, Serotonin, 5-HT1A
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Serotonin
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BDNF protein, human
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N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Grants and funding
This research was conducted by pooling data from studies supported by grants of the Oesterreichische Nationalbank (Anniversary Fund, project numbers: 11468, 12809, 13675) and the Austrian Science Fund (FWF P16549). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.