Vorhees-Williams-Skelton Lab

  • Autism, Immune Activation and Genetic Susceptibility

    Autism is a pervasive developmental disorder (PDD) characterized by abnormalities in social interaction, communication and behavior (repetitive / perseverative behaviors). The cause is unknown and treatments limited, but there is no doubt that the origin is prenatal; children are born with autism even if the symptoms do not appear clearly enough to diagnose it until eye contact, locomotion and language begin to emerge. Our lab is working to better understand the causes of this disorder now estimated by the CDC to occur in 1 out of every 88 births.

    Susceptibility genes have also been associated with autism. One of these is PTEN, which has multiple functions, including its actions as lipid and protein phosphatases that, through dephosphorylation, act as a tumor suppressor and negative growth regulator. PTEN mutations are associated with cell growth and tumorigenesis, and in the brain have been associated with autism. In collaboration with Steve Danzer, PhD, who has developed a PTEN brain-specific mutant mouse, we will be investigating this as a new model of autism-associated behavioral dysfunction.

    Two recent epidemiological studies have shown a significant (doubling to tripling) incidence of Autism Spectrum Disorder (ASD) in children born to women who took antidepressants during pregnancy.  One of these studies found that the largest fraction of the risk was from selective serotonin reuptake inhibitors (SSRIs), the largest group of antidepressants in current use.  Unfortunately, studies of this type cannot determine which antidepressant(s) may be causing ASD (if any) or if non-SSRI antidepressants are or are not similarly associated with increased ASR risk.  Nor can the human studies determine the molecular mechanisms of how antidepressants alter the developing brain to crease the risk of ASD.  Therefore, we testing the effects of two SSRI and one non-SSRI antidepressant given throughout early brain development in laboratory rats (from implantation to the end of major neurogenesis (which occurs postnatally in the rat but prenatally in humans)) to assess how the drugs affect brain development, neurotransmitters, receptors, and ASD-like behavior.  Not only do we wish to determine how antidepressants may lead to ASD-associated changes, but if different types of antidepressants carry different risks for inducing ASD-related changes in the offspring.