title: The tricks of the trait: neural implementation of personality varies with genotype-dependent serotonin levels.
abstract: Gray's Reinforcement Sensitivity Theory (RST) has developed into one of the most prominent personality theories of the last decades. The RST postulates a Behavioral Inhibition System (BIS) modulating the reaction to stimuli indicating aversive events. A number of psychiatric disorders including depression, anxiety disorders, and psychosomatic illnesses have been associated with extreme BIS responsiveness. In recent years, neuroimaging studies have implicated the amygdala-septo-hippocampal circuit as an important neural substrate of the BIS. However, the neurogenetic basis of the regulation of this behaviorally and clinically essential system remains unclear. Investigating the effects of two functional genetic polymorphisms (tryptophan hydroxylase-2, G-703T, and serotonin transporter, serotonin transporter gene-linked polymorphic region) in 89 human participants, we find significantly different patterns of associations between BIS scores and amygdala-hippocampus connectivity during loss anticipation for genotype groups regarding both polymorphisms. Specifically, the correlation between amygdala-hippocampus connectivity and Gray's trait anxiety scores is positive in individuals homozygous for the TPH2 G-allele, while carriers of at least one T-allele show a negative association. Likewise, individuals homozygous for the 5-HTTLPR L(A) variant display a positive association while carriers of the S/L(G) allele show a trend towards a negative association. Thus, we show converging evidence of different neural implementation of the BIS depending on genotype-dependent levels of serotonin. We provide evidence suggesting that genotype-dependent serotonin levels and thus putative changes in the efficiency of serotonergic neurotransmission might not only alter brain activation levels directly, but also more fundamentally impact the neural implementation of personality traits. We outline the direct clinical implications arising from this finding and discuss the complex interplay of neural responses, genes and personality traits in this context.
authors.affiliation: Department of Cognitive Psychology II, Johann Wolfgang Goethe University Frankfurt/Main, Germany. Electronic address: Hahn@psych.uni-frankfurt.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Hahn
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heinzel
authors.affiliation: Department of Cognitive Psychology II, Johann Wolfgang Goethe University Frankfurt/Main, Germany; Research Center of Marketing and Consumer Science, Katholieke Universiteit Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Notebaert
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany; LEAD Graduate School, University of Tübingen, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dresler
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Research Center Magnetic Resonance Bavaria, Würzburg, Germany; Department of Experimental Physics V, University of Würzburg, Würzburg, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jakob
authors.affiliation: Department of Cognitive Psychology II, Johann Wolfgang Goethe University Frankfurt/Main, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Windmann
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000033:anatomy & histology / Q000502:physiology; D001007:Anxiety / Q000235:genetics; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000033:anatomy & histology* / Q000502:physiology; D010551:Personality / Q000235:genetics*; D010554:Personality Disorders / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
keywords: Amygdala; Functional connectivity; Hippocampus; Reinforcement Sensitivity Theory; Serotonin transporter (5-HTT); Tryptophan hydroxylase-2 (TPH2)