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.

Keywords:

• Williams syndrome
• Anxiety
• Sociability
• DTI
• Uncinate fasciculus

We warmly thank all the participants, their families, and the Williams Syndrome Association for their kind and generous cooperation in these studies.

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by NICHD [grant number 033113], NINDS [grant number 22343], and the Oak Tree Philanthropic Foundation; and the National Science Foundation Graduate Research Fellowship Program under grant number 00039202 as part of Ms. Ng’s training.