title: Structural integrity of the limbic-prefrontal connection: Neuropathological correlates of anxiety in Williams syndrome.
abstract: Williams syndrome (WS) is a genetic condition characterized by a hypersocial personality and desire to form close relationships, juxtaposed with significant anxieties of nonsocial events. The neural underpinnings of anxiety in individuals with WS are currently unknown. Aberrations in the anatomical and microstructural integrity of the uncinate fasciculus (UF) have been recently implicated in social and generalized anxiety disorders. Based on these findings, we tested the hypothesis that the reported anxieties in individuals with WS share similar neuropathological correlates. Toward this end, diffusion tensor imaging (DTI) methods were employed to examine the microstructural integrity (fractional anisotropy, mean diffusivity, longitudinal diffusivity) of the UF in 18 WS and 15 typically developing adults (TD). Anxiety and sociability questionnaires were administered to determine associations with DTI indices of UF across groups. Results revealed comparable white matter integrity of the UF across groups, yet elevated subjective experience of anxiety in those with WS. Additionally, sociability and UF microstructural properties were dissociated across both groups. Whereas no relationships were found between DTI indices and anxiety in TD participants, strong negative associations were observed between these constructs in individuals with WS. Findings indicated that increased anxiety manifested by individuals with WS was associated with DTI measures of the UF and may signal structural or possibly physiological aberration involving this tract within the prefrontal-temporal network.
authors.affiliation: a Laboratory for Cognitive Neuroscience , Salk Institute for Biological Studies , La Jolla , CA , USA.|b Institute of Child Development , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Rowena
authors.initials: R
authors.lastname: Ng
authors.affiliation: c Multimodal Imaging Laboratory , University of California San Diego , La Jolla , CA , USA.|d Department of Neurosciences , University of California, San Diego School of Medicine , La Jolla , CA , USA.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: a Laboratory for Cognitive Neuroscience , Salk Institute for Biological Studies , La Jolla , CA , USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Järvinen
authors.affiliation: c Multimodal Imaging Laboratory , University of California San Diego , La Jolla , CA , USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Erhart
authors.affiliation: e Center for Integrated Neuroscience and Human Behavior , University of Utah , Salt Lake City , UT , USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Korenberg
authors.affiliation: a Laboratory for Cognitive Neuroscience , Salk Institute for Biological Studies , La Jolla , CA , USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Bellugi
authors.affiliation: c Multimodal Imaging Laboratory , University of California San Diego , La Jolla , CA , USA.|f Department of Radiology , University of California, San Diego School of Medicine , La Jolla , CA , USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Halgren
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001007:Anxiety / Q000209:etiology / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology*; D011795:Surveys and Questionnaires; D018980:Williams Syndrome / Q000150:complications / Q000473:pathology; D055815:Young Adult
keywords: Anxiety; DTI; Sociability; Uncinate fasciculus; Williams syndrome