Special Issue: New Concepts in Developing Brain Disorders—Autism


Extensive research throughout the international community has been conducted to better understand the etiology of pervasive neurodevelopmental disorders such as autism spectrum disorder (ASD). There are numerous reviews of both human studies and various animal models that highlight particular advancements in our understanding of ASD, but no coherent picture has yet emerged. We still do not fully understand the recent surge in ASD cases. Happe et al. (2006) argued for no single cause in the article, “Time to give up on a single explanation for autism.” Support for such a view is becoming increasingly accepted since there seems to be a strong case to be made in the areas of genetics, epigenetics, and in the contribution of environmental factors (Persisco and Bourgeron,2006; Fischbach and Lord,2010; Lajonchere and the ARGE Consortium,2010). The aim of these collective thematic papers is to provide some of the latest experimental findings from a variety of perspectives that several groups of neuroscientists around the world are exploring to further understand the etiology of these devastating neurodevelopmental disorders.

One of the areas of significant advancement highlights the importance of serotonin during neurodevelopment, and at least three prominent reviews (Gaspar et al.,2003; Scott and Deneris,2005; Homberg et al.,2009) have provided this novel perspective by looking at the perinatal effects of selective serotonin reuptake inhibitors (SSRIs) on central nervous system development. For example, Lin and his colleagues have suggested a rather novel hypothesis regarding the modification of the noradrenergic system in rat pups exposed to SSRIs and in monoamine oxidase A knock out mice. Additionally, Gaspar and her colleagues have developed new genetic models that examine the effects of serotonin depletion. Along these lines of evidence, Azimitia and his colleagues have provided support for this hypothesis with dystrophic serotonin axons in young autistic patients.

Whitaker-Azmitia and her colleagues have also provided a novel idea about the importance of the neuroendocrine system (especially oxytocin and estradiol) in sexual differentiation and its potential role in ASD. In addition, Page has proposed that certain ASD risk factors, especially related to oxytocin system, alter the development of certain neural circuits and influence social behavior.

Two prominent laboratories have used postmortem tissue from autistics and contributed their intriguing new findings. For example, Fatemi and his colleagues have provided extensive evidence for the altered expression of Fragile X mental retardation protein, metabotropic glutamate receptor 5, GABAa receptor beta 3 subtype, and glia responses in the vermis of autistic subjects. Furthermore, Blue and her colleagues provided neurochemical evidence of dysfunctional NMDA receptor expression in Mecp2-null mice as a potential new model for Rett syndrome.

Functional implications of the structural changes induced by drug exposure during early development are better understood using electrophysiology and behavioral paradigms. Three such articles have contributed in this front. For example, the laboratory of both Waterhouse and Berridge have come up new experimental strategies for investigating psychostimulant drugs as new models for ADHD and other attention related disorders. The laboratory of Edward used new social behavioral tests such as sniff time versus vicinity time as a new behavioral model for autismlike phenotypes. Lastly, Paul and his colleagues suggested that neonatal exposure of rats to antidepressants affects novelty and social interaction behaviors, providing potential clues of adverse antidepressant usage during pregnancy. In addition, ASD patients demonstrate altered cortical connections suggesting a “mis-wired brain” and these improper synaptic connections lead to deficits in information processing (Kelleher and Bear,2008; Gepner and Feron,2009). Along these lines, Blatt and Fatemi have implicated the importance of GABAergic neurons as biomarker to better understand the role of inhibitory system in the autistic brain.

This, of course, only represents a small fraction of the laboratories working on the issues of abnormal neurodevelopment and how it relates to ASD. Continued exploration of the potential causes for these neurodevelopmental disorders is extremely important for the health of the population as well as in reducing the financial burden associated with these devastating neurodevelopmental disorders.