Autism arises, at least in part, as a result of poor signaling between neurons, which disrupts the behavioral pathways necessary for social interactions, language development and motor control. At Stanford University, Thomas Südhof and his colleagues plan to study how proteins called neuroligins regulate neuronal signaling, in order to understand their role in those behavioral pathways and in autism.
Autism arises from mutations in the genome, but several studies have shown that many of these mutations occur de novo — that is, they are non-inherited mutations introduced during the parents’ gamete production. Jay Gingrich at the New York State Psychiatric Institute and his colleagues plan to study a mouse model of autism to investigate whether advanced paternal age is linked to a higher frequency of genomic aberrations.
The gene encoding the transcription factor FOXP1 is strongly implicated in the etiology of individuals with autism spectrum disorder (ASD) and of those with intellectual disability. FOXP1 is among the 40 highest-ranked candidate ASD risk genes (according to SFARI Gene). Brain-wide deletion of FOXP1 in mice results in altered behaviors relevant to ASD.
In a previously funded SFARI study of 100 children with autism spectrum disorder (ASD), Ruth O’Hara and her colleagues found that sleep-disordered breathing (SDB) — such as sleep apnea — occurs in more than 40 percent of children with ASD, a far higher rate than that seen in typically developing children. SDB is strongly linked to cognitive and behavioral deficits and elicits a systemic inflammatory response. Recent studies have focused on the role of microparticles (MPs) in SDB disorders. Cell-derived MPs are microvesicles of 0.05 to 1 micrometers, released through exocytic budding of the plasma membrane, following stimulation of different cell types.
Autism spectrum disorders comprise a wide constellation of neurobehavioral conditions that arise from abnormal patterns of brain development. In order to understand how autism-related behaviors emerge from alterations to the normal development of the brain, it is necessary to examine how neurons differ in their patterns of connectivity among various brain regions.
Accumulating evidence suggests that autism spectrum disorder symptoms arise from a disruption in the process of experience-dependent synaptic plasticity that normally occurs during critical periods of development. Critical periods are windows of time when appropriate sensory, motor and cognitive function are essential for the refinement and tuning up of brain circuits. Rett syndrome is recognized as one of the clearest genetic examples of autism, and is caused by mutations in the MeCP2 gene.
The core set of behavioral symptoms that define autism spectrum disorders can arise from a wide array of genetic and environmental causes. This many-to-one correspondence between genetic causes and behavioral phenotypes suggests that understanding and eventually treating autism may depend on identifying common intermediate biomarkers at the level of neural circuits or biochemical pathways.
Autism arises in early childhood, during a period of intense learning when many of the brain’s connections are modified by experience. Several autism-associated proteins also play important roles in memory formation.
A well-characterized microdeletion in the 22q11.2 chromosomal region is known to be associated with schizophrenia. There is growing evidence that duplications at this locus are also associated with autism. Joseph Gogos and his colleagues at Columbia University in New York have been studying the chain of molecular and cellular events arising from copy number variants (CNVs) at this locus, which may lead to altered brain connectivity.