Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study
Open accessAbstract
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.
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Previous work in our laboratory found that individual-specific environmental factors, rather than genetic factors, had the greatest effect on the limbic striatum.
“previous work in our laboratory (Stokes et al., 2013) on heritability of striatal dopamine synthesis capacity found that individual-specific environmental factors, rather than genetic factors, had the greatest effect on the limbic striatum”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Stokes et al., 2013
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“Nonetheless, previous work in our laboratory (Stokes et al., 2013) on heritability of striatal dopamine synthesis capacity found that individual-specific environmental factors, rather than genetic factors, had the greatest effect on the limbic striatum which is consistent with the interpretation…”
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- Authors
- Stokes, P. R. A., Shotbolt, P., Mehta, M. A., Turkheimer, E., Benecke, A., Copeland, C., Turkheimer, F. E., Lingford-Hughes, A. R., & Howes, O. D.
- Affiliations
- Hammersmith Hospital (GB)
- King's College London (GB)
- University of Virginia (US)
- Imperial College London (GB)
- Corresponding author
- Stokes, Paul R A
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2012-10-24
- Volume
- 38
- Issue
- 3
- Pages
- 485-491
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3547199
- OpenAlex
- W2099289869
- Cited by
- 37
- References
- 36
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 5
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- heritability, monozygotic twins, dizygotic twins, 18F-DOPA PET, sensorimotor striatum, limbic striatum, shared environmental effects, genetic and environmental factors, schizophrenia, addiction
- MeSH terms
- Adult, Corpus Striatum, Dihydroxyphenylalanine, Dopamine, Female, Humans, Male, Social Environment, Twins, Dizygotic, Twins, Monozygotic, Cohort Studies, Fluorodeoxyglucose F18, Positron-Emission Tomography
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