Early-life investigations of genetic & environmental factors contributing to neurodevelopmental disorder risk

Neurodevelopmental disorders are a group of childhood psychiatric diagnoses with symptoms that tend to persist into adulthood. This group of disorders include, but are not limited to, autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder, Tourette syndrome, and schizophrenia. While these disorders tend to have distinct constellations of symptoms, comorbidities are frequent, possibly pointing to overlapping pathologies between disorders. Neurodevelopmental disorders also share common affected brain regions, such as the prefrontal cortex, basal ganglia, and cerebellum.

The complex etiology of this disorder is further complicated by the large variety of genetic and environmental risk factors for abnormal development. Prior research has linked a variety of single gene mutations, chromosomal mutations, and epigenetic modifications with the development of NDDs. One such mutation is the copy number variation of chromosomal segment 16p11.2, which may be duplicated or deleted. These mutations have been associated with increased incidence of autism, attention deficit hyperactivity disorder, and intellectual disability. The duplication has also been associated with increased risk for schizophrenia. In chapter two, we examine the effects of 16p11.2 copy number variations on grooming in developing mice to understand how these mutations affect innate, repetitive behaviors.

Other work suggests that environmental factors such as maternal exposures to toxins, prenatal stress, adverse childhood experiences, and traumatic brain injury may also increase risk for neurodevelopmental disorders. Past research has associated cerebellar damage in childhood with widespread behavioral changes and early signs of autism spectrum disorder. In chapter three, we performed developmental and adult cerebellar lesions in rats and assessed effects on repetitive, anxiety-like, and social behaviors.