title: Nature or nurture? Determining the heritability of human striatal dopamine function: an [18F]-DOPA PET study.
abstract: Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions.
authors.affiliation: Psychiatric Imaging Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK. paul.stokes@imperial.ac.uk
authors.forename: Paul R A
authors.initials: PR
authors.lastname: Stokes
authors.forename: Paul
authors.initials: P
authors.lastname: Shotbolt
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.forename: Eric
authors.initials: E
authors.lastname: Turkheimer
authors.forename: Aaf
authors.initials: A
authors.lastname: Benecke
authors.forename: Caroline
authors.initials: C
authors.lastname: Copeland
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D012931:Social Environment; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D019788:Fluorodeoxyglucose F18; D004295:Dihydroxyphenylalanine; D004298:Dopamine