Preface

In this Special Issue on Autism: Modeling Human Brain Abnormalities in Developing Animal Systems, we have brought together clinical and basic science investigators to foster communication across these distinct research communities. As a sign of the significant progress made in the last decade thanks to research support from private autism foundations and the NIH, we are now in a position to define fundamental neurobiological mechanisms that contribute to human autism. Towards this goal, this issue features clinical scientists who have identified distinct brain regions as well as specific neurochemical systems that are altered in autism. This kind of focus in turn allows basic scientists to directly model the mechanisms that underlie generation of these regions and systems, and to hypothesize how pathogenetic processes could impact such mechanisms to produce autism brain abnormalities. We start with the identification of brain regions, in particular the amygdala and fusiform face area, whose dysfunction may underlie the core symptoms of social deficits and possibly language. The very earliest observations in the clinic and by neuroimaging indeed suggest that brain functional and structural abnormalities are already present at birth, and likely appear far earlier, during the embryonic period of brain development. Indeed, the neuropathology, the co-morbidity of autism with congenital syndromes, and the production of autism by environmental insults (teratogens) suggest that some autism results from events occurring during the first 8 weeks post-conception. Genetic studies have in fact found evidence supporting abnormalities in several molecular systems that play primary roles in prenatal brain formation. Based on these clinical observations several animal model systems have been explored. Both primate and rodent models examine the roles of neuropeptide systems that localize to amygdala and other forebrain regions and regulate a variety of social functions including recognition, communication and bond formation. Other models focus on the development and function of the hindbrain, especially the cerebellumwhich exhibits the most consistent pathological abnormality, a deficiency of Purkinje neurons. The several reviews describe the molecular genetic underpinnings necessary to generate the hindbrain and cerebellum as well as the serotonergic transmitter system, which is abnormal on human imaging, and whose development can be altered by teratogen exposures. These genetic networks are operative during the very same embryonic timeframe in the animal model as proposed in the human studies based on brain imaging, neuropathology, teratogenic insults and congenital syndromes. Finally, several papers describe how environmental factors, whether iatrogenic or of maternal origin, can alter brain development to produce components of the autism structural and behavioral phenotype. In summary, these studies demonstrate that by precisely characterizing a specific component of the autism phenotype (an endophenotype), whether structural or functional, this knowledge can be used to generate specific animal model systems. In turn, fundamental neurobiological mechanisms can be defined in the animal that subsequently translate into new approaches for further clinical study, and may allow design of novel therapeutic strategies. In the following paragraphs, a brief review of each paper is presented, highlighting findings and implications, and drawing the reader’s attention to other papers in this volume that address the same or related topics. I would like to acknowledge the efforts and patience of all the authors for their exciting contributions, and especially thank Ms. Donna Masters, Coordinator and Editorial Assistant to Dr. J. Regino Perez-Polo, for her ceaseless attention to this issue, without whom this project would not have been possible. In the first paper, Developmental deficits in social perception in autism: The role of the amygdala and fusiform face area, Schultz suggests that the primacy of the social defect in all varieties of autism spectrum disorders (ASD) may make it the best phenotypic entrance point for studying neurobiological mechanisms. Schultz suggests that the selective loss of social function with, in many cases, preservation of normal intelligence, argues against a pathogenetic model involving a general overall deficit in complex information processing. It is hypothesized that an early failure to attend to faces, possibly due to low emotional reward value, leads to social deficits in face and facial expression perception, and subsequently abnormalities in language development, which depends on shared experiences. Schultz reviews the literature on face perceptual abnormalities in autism and integrates it with fMRI data to www.elsevier.com/locate/ijdevneu Int. J. Devl Neuroscience 23 (2005) 117–124