title: Fear-specific amygdala function in children and adolescents on the fragile x spectrum: a dosage response of the FMR1 gene.
abstract: Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS.
authors.affiliation: Center for Mind and Brain, University of California, Davis, CA 95618, USA.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jessica
authors.initials: J
authors.lastname: Burris
authors.forename: Frederick
authors.initials: F
authors.lastname: Bassal
authors.forename: Kami
authors.initials: K
authors.lastname: Koldewyn
authors.forename: Sumantra
authors.initials: S
authors.lastname: Chattarji
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: David
authors.initials: D
authors.lastname: Hessl
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rivera
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000098:blood supply / Q000473:pathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D005133:Eye Movements / Q000502:physiology; D005239:Fear; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D010100:Oxygen; C497683:FMR1 protein, human
keywords: FMR1 gene; amygdala; emotion; fragile X syndrome; functional brain imaging