Behavioral and Molecular Changes Following Acute Sleep Deprivation in Juvenile Wild-Type and Shank3WT/ΔC Mice

Sleep is a critical to health and wellbeing, and lack of sleep can have numerous detrimental effects on human health. These effects can be overrepresented or exasperated in certain populations, such as those with autism spectrum disorders (ASD). Mutations in the Shank3DC gene have been used as a mouse model of autism, and these mice have been shown to have a distinct sleep phenotype. A popular measure of sleep deprivation effects is Novel Object Recognition (NOR), as sleep-deprived (SD) mice show disruptions to learning and memory. Sleep is hypothesized to play a key role in memory consolidation through homeostatic synaptic downscaling. Some key proteins involved in or mediating this process are Arc and mGluR5. The current study will analyze behavioral and molecular changes following SD in juvenile mice by administration of NOR to wild-type (WT) mice and Western Blotting of forebrains of WT and Shank3WT/DC mice for protein quantification. Due to their vulnerability, I hypothesized lack of novel object identification in NOR following both two-hour and four-hour sleep deprivation. I also expected increase of Arc, mGluR5, and SHANK3, with Shank3WT/DC animals having more intense responses. The study found juvenile WT mice to successfully learn only following a two-hour sleep deprivation, indicating a limited tolerance. Arc showed significant increase post sleep deprivation in both genotypes, while SHANK3 effects were only observed in Shank3WT/DC mice. Contrary to the hypothesis, mGluR5 did not show variability among groups. Further study is suggested with specified procedural modifications and larger data samples to include sex as a variable of analysis

In Addition to Stigma: Cognitive and Autism-Related Predictors of Mental Health in Transgender Adolescents

OBJECTIVE: Autism spectrum disorder (ASD) is significantly over-represented among transgender adolescents. Independently, ASD and gender diversity are associated with increased mental health risks. Yet, mental health in autistic-transgender adolescents is poorly understood. This study investigates mental health in the largest matched sample to date of autistic-transgender, non-autistic (allistic) transgender, and autistic-cisgender adolescents diagnosed using gold-standard ASD diagnostic procedures. In accordance with advancing understanding of sex/gender-related autism phenotypes, slightly subthreshold autistic diagnostic presentations (common in autistic girls/women) are modeled. METHOD: This study includes 93 adolescents aged 13-21, evenly divided between autistic-transgender, autistic-cisgender, and allistic-transgender groups; 13 transgender adolescents were at the margin of ASD diagnosis and included within a larger broad-ASD grouping. Psychological and neuropsychological evaluation included assessment of mental health, IQ, LGBT stigma, ASD-related social symptoms, executive functioning (EF), and EF-related barriers to achieving gender-related needs. RESULTS: Autistic-transgender adolescents experienced significantly greater internalizing symptoms compared to allistic-transgender and autistic-cisgender groups. In addition to stigma-related associations with mental health, ASD-related cognitive/neurodevelopmental factors (i.e., poorer EF and greater social symptoms) were associated with worse mental health: specifically, social symptoms and EF gender barriers with greater internalizing and EF problems and EF gender barriers with greater suicidality. Comparing across all ASD and gender-related groups, female gender identity was associated with greater suicidality. CONCLUSIONS: Parsing the heterogeneity of mental health risks among transgender youth is critical for developing targeted assessments and interventions. This study identifies ASD diagnosis, ASD phenotypic characteristics, and EF-related gender barriers as potential risks for poorer mental health in transgender adolescents