From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits

TY - JOUR

T1 - From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits

AU - Heinrich, Angela

AU - Nees, Frauke

AU - Lourdusamy, Anbarasu

AU - Tzschoppe, Jelka

AU - Meier, Sandra

AU - Vollstädt-Klein, Sabine

AU - Fauth-Bühler, Mira

AU - Steiner, Sabina

AU - Bach, Christiane

AU - Poustka, Luise

AU - Banaschewski, Tobias

AU - Barker, Gareth J

AU - Büchel, Christian

AU - Conrod, Patricia J

AU - Garavan, Hugh

AU - Gallinat, Jürgen

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Loth, Eva

AU - Mann, Karl

AU - Artiges, Eric

AU - Paus, Tomáš

AU - Lawrence, Claire

AU - Pausova, Zdenka

AU - Smolka, Michael N

AU - Ströhle, Andreas

AU - Struve, Maren

AU - Witt, Stephanie H

AU - Schumann, Gunter

AU - Flor, Herta

AU - Rietschel, Marcella

AU - IMAGEN Consortium

N1 - © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.

AB - Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.

KW - Adaptor Proteins, Signal Transducing

KW - Adolescent

KW - Brain

KW - Female

KW - Humans

KW - Impulsive Behavior

KW - Magnetic Resonance Imaging

KW - Male

KW - Risk Factors

KW - Schizophrenia

U2 - 10.1111/ejn.12201

DO - 10.1111/ejn.12201

M3 - SCORING: Journal article

C2 - 23551272

VL - 38

SP - 2941

EP - 2945

JO - EUR J NEUROSCI

JF - EUR J NEUROSCI

SN - 0953-816X

IS - 6

ER -