title: BDNF val66met association with serotonin transporter binding in healthy humans.
abstract: The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [11C]DASB positron emission tomography (PET) in a comparatively large cohort of 144 healthy individuals. We used a latent variable model to determine genetic effects on a latent variable (5-HTTLV), reflecting shared correlation across regional 5-HTT binding (amygdala, caudate, hippocampus, midbrain, neocortex, putamen and thalamus). Our data supported a significant BDNF val66met effect on 5-HTTLVsuch that met-carriers showed 2-7% higher subcortical 5-HTT binding compared with val/val individuals (P=0.042). Our data did not support a BDNF val66met effect in neocortex and 5-HTTLPR did not significantly predict 5-HTTLV. We did not observe evidence for an interaction between genotypes. Our findings indicate that met-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT level emerges and may represent an important molecular mediator of BDNF val66met effects on behavior and related risk for neuropsychiatric illness.
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: P M
authors.initials: PM
authors.lastname: Fisher
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.|Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Ozenne
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Adamsen
authors.affiliation: PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Lehel
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: W F C
authors.initials: WF
authors.lastname: Baaré
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: P S
authors.initials: PS
authors.lastname: Jensen
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O, Denmark.
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011699:Putamen / Q000378:metabolism; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D055815:Young Adult
chemical_list: D001596:Benzylamines; D019208:Brain-Derived Neurotrophic Factor; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C579455:BDNF protein, human