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Transl Psychiatry. 2018 Aug 30;8(1):169. doi: 10.1038/s41398-018-0222-7.

Epigenetic variance in dopamine D2 receptor: a marker of IQ malleability?

Author information

1
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. jakob.kaminski@charite.de.
2
Berlin Institute of Health (BIH), Kapelle Ufer 2, 10117, Berlin, Germany. jakob.kaminski@charite.de.
3
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
4
Max-Planck-Institute for Human Cognitive and Brainsciences, Stephanstraße 1a, 04103, Leipzig, Germany.
5
Social and Preventive Medicine, University of Potsdam, Am Neuen Palais 10, 14469, Potsdam, Germany.
6
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
7
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's Colleges, London, UK.
8
Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Liebigstrße 20a, 04103, Leipzig, Germany.
9
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
10
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
11
University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
12
Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College, London, UK.
13
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
14
Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
15
Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.
16
Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, 05405, USA.
17
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
18
Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, Berlin, Germany.
19
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes-Sorbonne Paris Cité, Maison de Solenn, Paris, France.
20
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes-Sorbonne Paris Cité; and AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France.
21
Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
22
Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
23
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
24
Department of Psychology, University College Dublin, Dublin, Ireland.

Abstract

Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.

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