Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

Borg, Jacqueline; Červenka, Simon; Kuja‐Halkola, Ralf; Matheson, Granville J.; Jönsson, Erik G.; Lichtenstein, Paul; Henningsson, Susanne; Ichimiya, Tetsuya; Larsson, Henrik; Stenkrona, Per; Halldin, Christer; Farde, Lars

doi:10.1038/mp.2015.147

Cited by 14 publications

(11 citation statements)

References 81 publications

(68 reference statements)

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“…There was a 2.5-fold range in D2R density. Similar ranges of variability have been reported also for other neuroreceptors [13][14][15][16][17][18][19].…”

Section: Interindividual Variability In Neuroreceptor Densitysupporting

confidence: 86%

“…This lack of knowledge limits the interpretation of changes in protein availability reported in psychiatric patients. In a recent attempt to elucidate this issue, we used PET in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain [14]. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for 5-HT 1A receptor availability in serotonergic projection areas and for D2R in striatum.…”

Section: Sources Of Variabilitymentioning

confidence: 99%

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Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Farde

Plavén-Sigray

Borg

et al. 2018

Phil. Trans. R. Soc. B

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Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

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“…There was a 2.5-fold range in D2R density. Similar ranges of variability have been reported also for other neuroreceptors [13][14][15][16][17][18][19].…”

Section: Interindividual Variability In Neuroreceptor Densitysupporting

confidence: 86%

Section: Sources Of Variabilitymentioning

confidence: 99%

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Farde

Plavén-Sigray

Borg

et al. 2018

Phil. Trans. R. Soc. B

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“…Individual variability in striatal D2/D3R availability is significantly heritable, as detected by a twin study (Borg et al, 2015). In addition, the similar pattern of associations between DRD2/ANKK1 TaqIA variants and D2/D3R availability with psychiatric and drug abuse risk has led to speculation that DRD2 ’s role in these disorders may be mediated by D2R.…”

Section: Introductionmentioning

confidence: 91%

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

Eisenstein

Bogdan

Love‐Gregory

et al. 2016

Synapse

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In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are non-selective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N‐[11C]methyl)benperidol ([11C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in 2 independent samples. Sample 1 (n = 39) was composed of obese and non-obese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5-12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1−), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1− was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [11C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states. GRAPHICAL ABSTRACT We investigated the difference in striatal dopamine D2 receptor binding, as measured by PET with (N-[11C]methyl)benperidol ([11C]NMB), between A1 allele carriers (A1+) and individuals homozygous for the A2 allele (A1−) of the DRD2/ANKK1 TaqIA single nucleotide polymorphism. In Study 1, A1+ had 5-12% less striatal [11C]NMB binding than A1−.

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“…The sample consisted of 50 healthy men: 12 were enrolled as control subjects in a series of different pharmacological studies (for details see Matheson et al (2015)); 38 in a twin study (Borg et al, 2016). Mean age was 30 ± 5 years (SD).…”

Section: Subjectsmentioning

confidence: 99%

Serotonin 5-HT_1A receptor binding and self-transcendence in healthy control subjects - a replication study using Bayesian hypothesis testing

Griffioen

Matheson

Červenka

et al. 2017

Preprint

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Objective: A putative relationship between markers for the serotonin system and the personality scale self-transcendence (ST) and its subscale spiritual acceptance (SA) has been demonstrated in a previous PET study of 5-HT1A receptor binding in healthy control subjects. The results could however not be replicated in a subsequent PET study at an independent centre. In this study, we performed a replication of our original study in a larger sample using Bayesian hypothesis testing to evaluate relative evidence both for and against this hypothesis.Methods: Regional 5-HT1A receptor binding potential (BPND) was examined in 50 healthy male subjects using PET with the radioligand [ 11 C]WAY100635. 5-HT1A availability was calculated using the simplified reference tissue model (SRTM) yielding regional BPND. ST and SA were measured using the Temperament and Character Inventory (TCI) questionnaire. Correlations between ST/SA scores and 5-HT1A BPND in frontal cortex, hippocampus and raphe nuclei were examined by calculation of default correlation Bayes factors (BFs) and replication BFs.Results: There were no significant correlations between 5-HT1A receptor binding and ST/SA scores. Rather, five of six replication BFs provided moderate to strong evidence for no association between 5-HT1A availability and ST/SA, while the remaining BF provided only weak evidence.Conclusion: We could not replicate our previous findings of an association between 5-HT1A availability and the personality trait ST/SA. Rather, the Bayesian analysis provided evidence for a lack of correlation. Further research should focus on whether other components of the serotonin system may be related to ST or SA. This study also illustrates how Bayesian hypothesis testing allows for greater flexibility and more informative conclusions than traditional p-values, suggesting that this approach may be advantageous for analysis of molecular imaging data.

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Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

Cited by 14 publications

References 81 publications

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

Serotonin 5-HT_1A receptor binding and self-transcendence in healthy control subjects - a replication study using Bayesian hypothesis testing

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Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

Cited by 14 publications

References 81 publications

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

Serotonin 5-HT1A receptor binding and self-transcendence in healthy control subjects - a replication study using Bayesian hypothesis testing

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Serotonin 5-HT_1A receptor binding and self-transcendence in healthy control subjects - a replication study using Bayesian hypothesis testing