A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans

• Published in: Biological psychology 2013-09, Vol.94 (1), p.74-81
• Main Authors: Cacciaglia, Raffaele, Nees, Frauke, Pohlack, Sebastian T., Ruttorf, Michaela, Winkelmann, Tobias, Witt, Stephanie H., Nieratschker, Vanessa, Rietschel, Marcella, Flor, Herta
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Alcoholism; Alcoholism - genetics; Alcoholism - pathology; Alcoholism and acute alcohol poisoning; Amygdala; Amygdala - blood supply; Amygdala - metabolism; Analysis of Variance; Behavioral psychophysiology; Biological and medical sciences; Conditioning, Classical - physiology; Extinction, Psychological - physiology; Fear - psychology; Fear conditioning; Female; Fundamental and applied biological sciences. Psychology; Galvanic Skin Response - genetics; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Medical sciences; NMDA receptor; Oxygen - blood; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Receptors, N-Methyl-D-Aspartate - genetics; Reflex, Startle; Single nucleotide polymorphism; Toxicology; Young Adult
• ISSN: 0301-0511; 1873-6246
• DOI: 10.1016/j.biopsycho.2013.05.006

•We used an imaging genetics approach during fear conditioning in healthy people.•Risk variant for alcoholism in GRIN2A affects amygdala activity during conditioning.•Risk variant for alcoholism in GRIN2A affects insula activity during conditioning.•These reduced responses may represent an intermediate phenotype for alcoholism. 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.