Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including "axon guidance" and "regulation of actin cytoskeleton." In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

An identity-based motivational model of the effects of perceived discrimination on health-related behaviors

Perceived discrimination is associated with increased engagement in unhealthy behaviors. We propose an identity-based pathway to explain this link. Drawing on an identity-based motivation model of health behaviors (Oyserman, Fryberg, & Yoder, 2007), we propose that erceptions of discrimination lead individuals to engage in ingroup-prototypical behaviors in the service of validating their identity and creating a sense of ingroup belonging. To the extent that people perceive unhealthy behaviors as ingroup-prototypical, perceived discrimination may thus increase motivation to engage in unhealthy behaviors. We describe our theoretical model and two studies that demonstrate initial support for some paths in this model. In Study 1, African American participants who reflected on racial discrimination were more likely to endorse unhealthy ingroup-prototypical behavior as self-characteristic than those who reflected on a neutral event. In Study 2, among African American participants who perceived unhealthy behaviors to be ingroup-prototypical, discrimination predicted greater endorsement of unhealthy behaviors as self-characteristic as compared to a control condition. These effects held both with and without controlling for body mass index (BMI) and income. Broader implications of this model for how discrimination adversely affects health-related decisions are discussed.