title: CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans.
abstract: Cyclic AMP response element-binding protein (CREB) contributes to adaptation of mesocorticolimbic networks by modulating activity-regulated transcription and plasticity in neurons. Activity or expression changes of CREB in the nucleus accumbens (NAc) and orbital frontal cortex (OFC) interact with behavioral changes during reward-motivated learning. However, these findings from animal models have not been evaluated in humans. We tested whether CREB1 genotypes affect reward-motivated decisions and related brain activation, using BOLD fMRI in 224 young and healthy participants. More specifically, participants needed to adapt their decision to either pursue or resist immediate rewards to optimize the reward outcome. We found significant CREB1 genotype effects on choices to pursue increases of the reward outcome and on BOLD signal in the NAc, OFC, insula cortex, cingulate gyrus, hippocampus, amygdala, and precuneus during these decisions in comparison with those decisions avoiding total reward loss. Our results suggest that CREB1 genotype effects in these regions could contribute to individual differences in reward- and associative memory-based decision-making.
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany Laboratory of Behavioral Neuroscience, National Institute of Aging, Baltimore, MD 21224-6825, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany Department of General Psychology, Technical University Dresden, Dresden 01069, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Mohr
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany Grindel Biocenter and Zoological Museum, Institute for Humanbiology, University Hamburg, Hamburg 20146, Germany.
authors.forename: Esther K
authors.initials: EK
authors.lastname: Diekhof
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Vieker
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Goya-Maldonado
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Trost
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Krämer
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Keil
authors.affiliation: Max-Planck-Institute for Psychiatry, Munich 80804, Germany.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Göttingen 37075, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003657:Decision Making / Q000502:physiology*; D056344:Executive Function / Q000502:physiology; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012201:Reward; D055815:Young Adult
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D010100:Oxygen
keywords: CREB1; decision-making; fMRI; genetics; reward