Opioids have long been implicated in social behaviors. Reducing opioid activity increases affiliative social behaviors and social reward-seeking while lowering stereotypies and self-injurious behaviors. The specific role of opioid blockers in complex social cognition, however, requires more investigation.
It is well established that homeostatic signaling systems interface with the mechanisms of developmental and learning-related plasticity to achieve stable yet flexible neural function and animal behavior. Experimental evidence from organisms as diverse as Drosophila, mice and humans demonstrates that homeostatic signaling systems stabilize neural function through the modulation of synaptic transmission, ion channel abundance and neurotransmitter receptor trafficking. At a fundamental level, if homeostatic plasticity is compromised, the nervous system is likely to be more sensitive to perturbations. Graeme Davis and his colleagues speculate that impaired homeostatic plasticity could contribute to autism by making the developing nervous system vulnerable to perturbations of any origin, including genetic, environmental or immunological stresses.
Multiple autism spectrum disorders share similar neuronal deficits at the molecular and cellular levels. Understanding the mechanism underlying those deficits helps researchers identify valuable targets for therapeutic development.
Benjamin Cheyette and his colleagues at the University of California, San Francisco have discovered several variations in the sequence of the DIXDC1 gene in individuals with autism, using DNA obtained from the Simons Simplex Collection. DIXDC1 encodes a protein involved in communication between neurons during development. This cell communication pathway, known as the WNT signaling pathway, has been implicated in autism by sequence findings involving other genes, such as CHD8.
Autism appears to be caused by a complex interplay of genetic and environmental factors. Over the past decade, scientists have established multiple animal models of autism using both genetic and environmental manipulations, demonstrating the presence of communication and social behavior deficits in these animals, as well as the presence of repetitive behaviors characteristic of individuals with autism. Randy Blakely and his colleagues at Vanderbilt University in Nashville, Tennessee, believe that the activation of a class of enzymes known as p38-alpha MAP kinases (p38-alpha MAPK) may underlie the ability of both genetic and environmental factors to produce autism.
Understanding how genetic defects that cause autism lead to abnormal neurodevelopment is critical to developing mechanism-based treatments. One particularly important question is whether different genetic defects produce autism traits in completely different ways, or whether alterations in different genes trigger a cascade of cellular changes that overlap and ultimately lead to autism by the same biochemical mechanism. JamesGusella and his colleagues at Massachusetts General Hospital aim to explore this question by using cutting-edge genome modification techniques to compare the effects of different autism-linked genetic traits in cultured human stem cells and neurons.
Illness or infections during early pregnancy are associated with increased incidence of autism. In pregnant mice, exposure to viral or bacterial agents alters fetal brain development, and pups show behavioral changes that are analogous to features seen in autism.
Immune‐related genes and immune responses to environmental stimuli are receiving attention due to their potential involvement in several neurodevelopmental disorders, including autism. Immune‐related genes have been associated with autism and maternal infection has been found to be the most compelling environmental risk factor for the disorder. Additionally, immune molecules have been shown to play many roles throughout brain development, including the initial establishment of synaptic connections, as well as synaptic plasticity.
Anatomic and molecular features observed in the brains of individuals with autism suggest that abnormalities in early embryonic development underlie the development of autism. Mutations in a gene called CHD8 are the most commonly identified mutations associated with autism. How CHD8 influences the disorder remains unknown, but observations that children with autism and CHD8 mutations have abnormally large heads (macrocephaly) support the possibility that CHD8 functions in regulating brain growth during development.
Mutations in hundreds of genes may predispose individuals to autism, but no common feature characterizes these genes, little is known about the functions of many of them and it remains unclear how mutations in these genes promote autism pathogenesis. Multiple autism-associated mutations have been identified in genes encoding neuroligins — cell-adhesion molecules that are essential for the organization of synapses, or the junctions between neurons, and for synapse property specification, during which neuroligins contribute to organizing synapse properties.