Simons Foundation

While autism clearly involves altered function of the central nervous system, the neuropathology of the disorder remains controversial. This is due in part,to the enormous complexity of the disorder, which likely has many causes and many biological trajectories. It is also due to the fact that few neuroimaging studies involve very young children or severely affected individuals. This lack of information is compounded by the fact that findings at the magnetic resonance imaging (MRI) level of analysis cannot be confirmed and extended to the cellular level due to a lack of postmortem brains.

Advances in molecular genetics have implicated a variety of genetic variations in autism, yet understanding of what these variations mean is still limited. Advances in classification of diseases have made autism among the most reliably diagnosed neurodevelopmental or neuropsychiatric disorders. But symptoms used to define autism are likely outcomes of earlier disruptions in normative social and communication development rather than causally linked to genetic perturbations.

A central goal in neuroscience is determining the genetic basis of neurological disorders — from autism to brain tumors. Many of these pathological states result from defects in gene regulatory programs that are fundamental to all cell types but lead to dysfunction specifically within the nervous system. Gail Mandel investigates the basis of this phenomenon and has identified cell-cell interactions between neurons and glia involved in pathological states of brain development. Mandel has ameliorated the neuropathology of one autism spectrum disorder, Rett syndrome, by genetically replacing the defective MeCP2 gene with a good copy of the gene in astrocytes – glia cells in the brain. She is now exploring the underlying mechanisms crucial for neuronal signaling.