title: Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.
abstract: A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mental Illness Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA; CIBERSAM, Autonoma University, Fundacion Jimenez Diaz and Ramon y Cajal Hospital, Madrid, Spain. Electronic address: mercedes.perez@mssm.edu.
authors.forename: M Mercedes
authors.initials: MM
authors.lastname: Perez-Rodriguez
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mental Illness Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA.
authors.forename: Antonia S
authors.initials: AS
authors.lastname: New
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Goldstein
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mental Illness Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosell
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9412, USA.
authors.forename: Qiaoping
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9412, USA.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9412, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Hodgkinson
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9412, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mental Illness Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mental Illness Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA.
authors.forename: Erin A
authors.initials: EA
authors.lastname: Hazlett
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000000981:diagnostic imaging*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004644:Emotions / Q000502:physiology; D005260:Female; D005838:Genotype; D006185:Habituation, Psychophysiologic / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D010775:Photic Stimulation / Q000379:methods; D012569:Schizotypal Personality Disorder / Q000000981:diagnostic imaging / Q000235:genetics / Q000523:psychology; D014633:Valine / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
keywords: Amygdala; BDNF; Borderline personality disorder; Emotion regulation; Extinction; Habituation