title: The impact of serotonin transporter genotype on default network connectivity in children and adolescents with autism spectrum disorders.
abstract: Compared to healthy controls, individuals with autism spectrum disorders (ASD) have weaker posterior-anterior connectivity that strengthens less with age within the default network, a set of brain structures connected in the absence of a task and likely involved in social function. The serotonin transporter-linked polymorphic region (5-HTTLPR) genotypes that result in lowered serotonin transporter expression are associated with social impairment in ASD. Additionally, in healthy controls, low expressing 5-HTTLPR genotypes are associated with weaker default network connectivity. However, in ASD, the effect of 5-HTTLPR on the default network is unknown. We hypothesized that 5-HTTLPR's influence on posterior-anterior default network connectivity strength as well as on age-related changes in connectivity differs in the ASD group versus controls. Youth with ASD and healthy controls, ages 8-19, underwent a resting fMRI acquisition. Connectivity was calculated by correlating the posterior hub of the default network with all voxels. Triallelic genotype was assessed via PCR and Sanger sequencing. A genotype-by-diagnosis interaction significantly predicted posterior-anterior connectivity, such that low expressing genotypes (S/S, S/LG, LG/LG) were associated with stronger connectivity than high expressing genotypes (LA/LA, S/LA, LA/LG) in the ASD group, but the converse was true for controls. Also, youth with ASD and low expressing genotypes had greater age-related increases in connectivity values compared to those with high expressing genotypes and controls in either genotype group. Our findings suggest that the cascade of events from genetic variation to brain function differs in ASD. Also, low expressing genotypes may represent a subtype within ASD.
authors.affiliation: Department of Psychology, University of Michigan, 530 Church St., Ann Arbor, MI 48109, USA.
authors.forename: Jillian Lee
authors.initials: JL
authors.lastname: Wiggins
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Peltier
authors.forename: Jirair K
authors.initials: JK
authors.lastname: Bedoyan
authors.forename: Melisa
authors.initials: M
authors.lastname: Carrasco
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.forename: Donna M
authors.initials: DM
authors.lastname: Martin
authors.forename: Catherine
authors.initials: C
authors.lastname: Lord
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Monk
keywords: Autism; Default network; Development; Functional MRI; Resting connectivity; Serotonin transporter gene