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Brain Struct Funct. 2016 Jan;221(1):103-14. doi: 10.1007/s00429-014-0895-5. Epub 2014 Oct 16.

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.

Author information

1
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
2
Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
3
MR Centre of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
4
Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, Heidelberg University, Mannheim, Germany.
5
Institute of Psychiatry, King's College, London, UK.
6
Institute of Neuroscience, Trinity College, Dublin, Ireland.
7
University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
8
Department of Psychiatry, Université de Montreal, CHU St. Justine Hospital, Montreal, Canada.
9
Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.
10
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
11
Department of Psychiatry and Psychology, University of Vermont, Burlington, USA.
12
Physikalisch-Technische Bundesanstalt, Berlin, Germany.
13
McGill University and Génome Québec Innovation Centre, Montreal, Canada.
14
Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 "Imaging and Psychiatry", Orsay, France.
15
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
16
Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
17
Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry and Child Development, Stanford University School of Medicine, Stanford, USA.
18
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
19
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. lukas.pezawas@meduniwien.ac.at.

Abstract

Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder.

KEYWORDS:

Adolescents; Catechol-O-methyltransferase; Cognition; Dopamine; Functional neuroimaging; Magnetic resonance imaging

PMID:
25319752
PMCID:
PMC4667398
DOI:
10.1007/s00429-014-0895-5
[Indexed for MEDLINE]
Free PMC Article

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