Autism - Interview with Joseph Piven, M.D.

n our Special Topics analysis of autism research over the past decade, Dr. Joe Piven ranks at #9, with 54 papers on the topic cited a total of 918 times. In the broader ISI Essential Science Indicators Web product, Dr. Piven’s work can be found in the field of Psychiatry/Psychology. Dr. Piven is the Director of the Neurodevelopmental Disorders Research Center at the University of North Carolina, Chapel Hill. In the interview below, he discusses the origins and development of his highly cited work on autism.

What are the circumstances which led to your work?

“…we now have some of the infrastructure in place to make more rapid progress in understanding the pathogenesis of autism.”

During my psychiatry residency training at Johns Hopkins I had the good fortune to spend six months with Professor Sir Michael Rutter at the Institute of Psychiatry in London. There I had a very exciting introduction into research in child behavior and development as well as clinical training in autism. My next opportunity came upon returning to Hopkins when Dr. Susan Folstein, who had written the first twin paper on autism with Professor Rutter, documenting the importance of genetic factors, was funded by the NIH to do a cross-national study (also with Professor Rutter) on what we now refer to as the broad autism phenotype. Finally, Joe Coyle, my boss and Director of Child Psychiatry at Hopkins, was able to help me get salary support from the John Merck Foundation, to work with Susan for three years in a post-doctoral research fellowship in psychiatric genetics. These three training and funding opportunities were critical in providing the foundation for my later work.

Would you describe the significance of this work for your field?

My research has been aimed at understanding the pathogenesis of autism by defining the behavioral and biological phenotypes that are most useful for teasing apart the complex etiologies underlying this condition. For the majority of the last 60 years, since autism was first described, we have defined autism largely on the basis of its most clinically relevant features—social deficits, language abnormalities, and stereotyped behaviors. Clearly these are not necessarily the most important characteristics relating to the underlying biology or genetics of this disorder.

Our group has studied personality, language, and cognitive characteristics in non-autistic relatives of autistic individuals; we believe these characteristics are genetically related to autism and are a qualitatively similar but milder expression of the genes that cause autism. Studying these milder characteristics provides the opportunity to disaggregate these characteristics and see how they might segregate in families; it allows us to examine what might be the behavioral forme fruste of this condition; and, finally, it provides more affected individuals for study in "autism families" and therefore may increase our power or ability to find autism genes. We have employed this strategy successfully in our linkage study of autism, using additional phenotypic information on autistic individuals and parents. We are currently studying the neuropsychological basis of autism and the broad autism phenotype in a sample of high IQ autistic individuals and their family members, to provide more incisive approaches (and, in particular, approaches tied to specific brain structures based on lesion studies in humans) to defining the phenotype.

The other area of our research has been in describing brain structure in autism using MRI. We were the first to suggest that the brain volumes in autism are increased. This finding has become one of the few biological hallmarks of autism and has opened a large area of study into how early brain development leads to this phenomenon.

How much has this research advanced since you first started publishing on it?

Both areas—studies of the broad autism phenotype and MRI studies of brain structure in autism—have greatly expanded in recent years. In the late 1980s and early ‘90s we were more or less alone in studying the broad autism phenotype. This area of research has become a staple in the field and is currently the subject of study by many groups, some of whom are applying these results, as we are, to genetic linkage data. In the mid-1990s, with the emergence of functional imaging, I had difficulty raising interest in our findings about brain size and the volume and shape of substructures in autism. Recently, studies by several investigators have moved this area of research forward by showing that brain size changes can be documented in very early childhood. Now there is great interest in MRI studies of early brain development in autism.

Where do you see this research going 10 years from now?

I expect that we will have substantial advances in understanding the brain and behavioral phenotypes in autism—with, in particular, research advances in structural and functional imaging and perhaps in the area of animal models. My hope is that over the next 10 years we will have convincingly identified some of the major susceptibility genes in autism. This would certainly provide a giant leap forward in our understanding of autism and allow us to meaningfully tease apart the substantial heterogeneity in this condition, link genetic abnormalities to specific brain-behavior phenotypes, and develop more rationally derived approaches to treatment. Certainly with the substantial increases in NIH funding for Centers (with the CPEA and STAART Center initiatives) and the dramatic expansion in the number of interested investigators and research on autism, we now have some of the infrastructure in place to make more rapid progress in understanding the pathogenesis of autism.

Joseph Piven, M.D.
University of North Carolina
Chapel Hill, NC, USA

ESI Special Topics, February 2004
Citing URL - http://www.esi-topics.com/autism/interviews/JosephPiven.html