Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
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Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults. / Meyer, Bernhard M; Huemer, Julia; Rabl, Ulrich; Boubela, Roland N; Kalcher, Klaudius; Berger, Andreas; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavan, Hugh; Heinz, Andreas; Ittermann, Bernd; Jia, Tianye; Lathrop, Mark; Martinot, Jean-Luc; Nees, Frauke; Rietschel, Marcella; Smolka, Michael N; Bartova, Lucie; Popovic, Ana; Scharinger, Christian; Sitte, Harald H; Steiner, Hans; Friedrich, Max H; Kasper, Siegfried; Perkmann, Thomas; Praschak-Rieder, Nicole; Haslacher, Helmuth; Esterbauer, Harald; Moser, Ewald; Schumann, Gunter; Pezawas, Lukas.
in: BRAIN STRUCT FUNCT, Jahrgang 221, Nr. 1, 01.2016, S. 103-14.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
AU - Meyer, Bernhard M
AU - Huemer, Julia
AU - Rabl, Ulrich
AU - Boubela, Roland N
AU - Kalcher, Klaudius
AU - Berger, Andreas
AU - Banaschewski, Tobias
AU - Barker, Gareth
AU - Bokde, Arun
AU - Büchel, Christian
AU - Conrod, Patricia
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Frouin, Vincent
AU - Gallinat, Jurgen
AU - Garavan, Hugh
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Jia, Tianye
AU - Lathrop, Mark
AU - Martinot, Jean-Luc
AU - Nees, Frauke
AU - Rietschel, Marcella
AU - Smolka, Michael N
AU - Bartova, Lucie
AU - Popovic, Ana
AU - Scharinger, Christian
AU - Sitte, Harald H
AU - Steiner, Hans
AU - Friedrich, Max H
AU - Kasper, Siegfried
AU - Perkmann, Thomas
AU - Praschak-Rieder, Nicole
AU - Haslacher, Helmuth
AU - Esterbauer, Harald
AU - Moser, Ewald
AU - Schumann, Gunter
AU - Pezawas, Lukas
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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.
U2 - 10.1007/s00429-014-0895-5
DO - 10.1007/s00429-014-0895-5
M3 - SCORING: Journal article
C2 - 25319752
VL - 221
SP - 103
EP - 114
JO - BRAIN STRUCT FUNCT
JF - BRAIN STRUCT FUNCT
SN - 1863-2653
IS - 1
ER -
