title: A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans.
abstract: People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (rs2072450) in the NR2A subunit-containing N-methyl-d-aspartate (NMDA)-receptor. These results indicate that rs2072450 might confer risk for alcohol dependence through deficient fear acquisition indexed by a diminished amygdala response during aversive learning, and provide a neural basis for a weak behavioral inhibition previously documented in individuals at high risk for alcohol dependence. Carriers of the risk variant additionally exhibit dampened insula activation, a finding that further strengthens our data, given the importance of this brain region in fear conditioning.
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cacciaglia
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Pohlack
authors.forename: Michaela
authors.initials: M
authors.lastname: Ruttorf
authors.forename: Tobias
authors.initials: T
authors.lastname: Winkelmann
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology*; D000679:Amygdala / Q000098:blood supply / Q000378:metabolism*; D000704:Analysis of Variance; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000523:psychology*; D005260:Female; D005712:Galvanic Skin Response / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013216:Reflex, Startle; D055815:Young Adult
chemical_list: C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010100:Oxygen
keywords: Alcoholism; Amygdala; Fear conditioning; NMDA receptor; Single nucleotide polymorphism