title: Aversive learning in adolescents: modulation by amygdala-prefrontal and amygdala-hippocampal connectivity and neuroticism.
abstract: Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS- never followed by the US). During acquisition (CS+/- differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Jelka
authors.initials: J
authors.lastname: Tzschoppe
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: 1] King's College London, Institute of Psychiatry, London, UK [2] Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Dublin, UK.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.affiliation: Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: 1] INSERM CEA Unit 1000 'Imaging and Psychiatry', Institut National de la Santé et de la Recherche Médicale, University Paris Sud, Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Neuroimaging Center and Department of Psychiatry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Aandreas
authors.initials: A
authors.lastname: Ströhle
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Struve
authors.affiliation: Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D001008:Anxiety Disorders / Q000473:pathology*; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D000075384:Neuroticism; D010100:Oxygen / Q000097:blood; D010555:Personality Inventory; D017397:Prefrontal Cortex / Q000098:blood supply / Q000503:physiopathology*; D011601:Psychophysics
chemical_list: D010100:Oxygen