UC San Diego

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by a microdeletion in chromosomal region 7q11.23 affecting approximately 25-28 genes. Individuals with this disorder display a unique hypersocial phenotype involving a seemingly uninhibited social approach, alongside several physiological and intellectual impairments. Many studies have characterized the genetic and behavioral phenotype of WS, however due to WS infrequency, there is limited research on how the genetic deletion affects neuroanatomical structure. The amygdala is a brain structure pivotal for the regulation of social and emotional behavior. Disruptions to the inhibitory interneuron system within the amygdala have been documented in other neurodevelopmental disorders, but not yet examined in WS. Through unbiased stereological and immunohistochemical approach, parvalbumin-positive (PV+) inhibitory interneuron density was measured within the lateral, basal, accessory basal and central nuclei of the amygdala in four post mortem human brains of individuals with WS and four matched controls. There was no significant difference of PV+ inhibitory interneuron density in WS compared to neurotypical controls in all amygdaloid nuclei. However, for both groups, the lateral nucleus demonstrated a regional specialization of PV+ interneurons not seen in the other nuclei examined. This is the first study to quantify GABAergic inhibitory interneuron density within the amygdala of WS individuals and one of a handful of studies to quantify interneuron density in the human brain. This study contributes important findings for future research that aim to examine neuronal mechanisms within WS and other neurological disorders involving atypical social behaviors in which inhibitory circuitry may be affected.