Autism Research at the Duke Center for Human Genetics


Autism is a chronic, nonprogressive developmental disorder. Individuals with autism have a unique set of symptoms in three areas: socialization (interaction with others), communication, and behavior. Autism is a common disorder, when other diagnoses such as pervasive developmental disorder (PDD), pervasive developmental disorder (not otherwise specified – PDD-NOS), and Asperger’s disorder are included in the spectrum.Autism is a complex genetic disorder thought to be caused by one or more genes, either acting alone or together with other factors. Through the Medical Genetics collaborative research study into the hereditary basis of autism, we hope to find the gene(s) that leads to autism. Finding these gene(s) will provide valuable insight into how the disorder is caused and will hopefully lead to improved diagnostic and treatment modalities.

Can Autism Be Inherited?

We are often asked the question, Am I at risk for having a child with autism or having another child with autism? The answer is not simple since autism has many causes. Some individuals may have a genetic form of autism. If possible, the underlying cause for the autistic-like behavior must be identified. Several inherited disorders are associated with autistic-like behavior. Some of these disorders include Fragile X Syndrome, Tuberous Sclerosis Complex (TSC), and Phenylketonuria (PKU). When a diagnosis of autistic disorder is made by a health care provider, it is important to determine whether the behavior is the result of one of these well known genetic disorders. If specific testing indicates one of these disorders is responsible for the behavior, the recurrence risk and perhaps the medical treatment will be altered.In most cases, there is no specific cause for autism in an individual. In these instances, the autism is said to be idiopathic, meaning that the behavior is secondary to an unknown cause. These non-specific answers can be frustrating for parents or family members who would like some explanation.

In this research study, we include individuals and families with idiopathic autism because these are the individuals most likely to carry the gene or genes that cause autism. By finding the genetic factors that play a role in the development of autism, we will someday be able to provide accurate recurrence risks to individuals and families as well as develop better treatments.

For families that have one child with idiopathic autism, there is an increased risk of having another child with autism. This recurrence risk is estimated to be about four percent which is greater than that found in families that do not have a child with autism.

Spiker D., Lotspeich L., Kraemer H.C., Hallmayer J., McMahon W., Petersen P.B., Nicholas P., Pingree C., Wiese-Slater S., Chiotti C. et al. Genetics of autism from 37 multiplex families: American Journal of Medical Genetics 54:1, 27-35, 1994.

Evidence Against X-linkage as a Major Cause of Autism

Since it is a known fact that more males have autism than females, researchers believed that autism might be associated with a non-working gene on the X chromosome. Recent data for our group and others have shown that it is unlikely that a gene on the X chromosome causes the majority of cases of autism.

How do we know this? By studying many different families in which more than one member has autism, or a variant of autism such as Asperger’s syndrome or PDD, we have seen that in a number of families the “gene” is passed through the father to a male child with autism. Since a father transmits an X chromosome only to his daughters and not his sons, the “gene” cannot be on the X chromosome in these families.

Cuccaro M.L., Wolpert C.M., McClintock D.E., Abramson R., Beaty L.M., Storoschuk S., Zimmerman A., Frye V., Porter N., Cook E., Stevenson R., DeLong G.R., Wright H.H., Pericak-Vance, M.A. Familial aggregation in autism: Evidence against X-linkage as a major genetic etiology. American Society of Human Genetics 1996.

Hallmayer J., Spiker D., Lotspeich L., McMahon W.M., Petersen P.B., Nicholas P., Pingree C., Ciaranello R.D. Male-to male transmission in extended pedigrees with multiple cases of autism. American Journal of Medical Genetics. 67:13-18, 1996.

Serotonin and Autism: What We Know So Far

Serotonin is a chemical that functions as a neurotransmitter (chemical communicator) in our brains. (Specifically, serotonin is concentrated in a part of the brain stem called the raphe nucleus). Serotonin is also present in certain blood cells called platelets. It is thought to be involved in inducing sleep, sensory perception, temperature regulation, and control of mood. Serotonin is of interest to autism researchers because some individuals with autism have consistently been found to have high levels of serotonin in their blood stream platelets. However, it is unclear what a high serotonin level signifies.Dr. Cuccaro and his colleagues at W.S. Hall Psychiatric Institute/USC School of Medicine in Columbia, South Carolina may have discovered an important clue. They conducted a study that looked at the level of blood (platelet) serotonin and the verbal ability of individuals with autism and their immediate relatives. Using a well accepted IQ test (Wechsler scales), these researchers found that individuals with high serotonin platelet or blood levels, had lower verbal ability scores. However, other measurements of intellectual abilities were not changed, including visual-spatial ability or memory. Intelligence is a combination of many different abilities including verbal, visual-spatial ability, memory and other areas.

What does this mean for individuals with autism and their immediate relatives? First, it provides one more biological clue about autism. While not all individuals with autism have high blood serotonin levels, many individuals do. Perhaps individuals with autism and high serotonin levels have one type of autism or perhaps high blood serotonin levels influence the signs and symptoms associated with autism. More research is needed before the relationship between serotonin levels and autism is understood.

Currently, a high or low blood serotonin level does not alter in any way how individuals with autism are managed medically. Occasionally, medications called serotonin reuptake inhibitors (e.g. Fluoxetine, Sertraline and Paroxetine) are prescribed for some individuals with autism. (This type of medication is also widely used to treat depression). Serotonin reuptake inhibitors keep serotonin in the brain longer so that its function as a chemical communicator is further enhanced. Studies in different populations of autistic individuals will help establish which individuals with autism will benefit from serotonin reuptake inhibitors or other drugs that influence blood and brain serotonin levels.

Cuccaro, M.L., Wright, H.H., Abramson, R.K., Marstellar, F.A., Valentine, J. Whole-blood serotonin and cognitive functioning in autistic individuals and their first-degree relatives. The Journal of Neuropsychiatry and Clinical Neurosciences. 1993; 5: 94-101.

Total Brain Volume Can Be Greater In Individuals with Autism

Thirty eight high-quality magnetic resonance image (MRI) scans of individuals with autism who were more than 12 years old were obtained. In addition, 38 MRIs of individuals over 12 years of age who did not have autism were also obtained. These MRIs were used as controls. Through careful measurement of the volume of the brain, Piven et al. reported that in almost half of the individuals with autism, the total brain volume was greater than in individuals without autism.These results confirm earlier MRI findings reported by the same group. These results suggest a problem in brain development (as opposed to a later injury). Unpublished data suggest that the enlargement may occur in particular regions of the brain and is not a generalized phenomenon. These results should provide important clues about the neurobiology of autism. For example, a new group of genes that are responsible for brain growth have recently been discovered. Abnormalities in these genes may underlie our findings of regional brain enlargement in autism. Also, since brain enlargement occurred in almost half (46%) of the subjects studied, brain size and shape may aid us in eventually identifying subgroups of autistic individuals with different causes for their autism. Dr. Piven and his associates are continuing to study imaging data and will be trying to obtain further funding to follow-up these results over the next year.

Piven J., Arndt S., Bailey J., Havercamp S., Andreasen N.C., Palmer P. An MRI study of brain size in autism. American Journal of Psychiatry: 12: 1145-1149, 1995.

Improvement In Autistic Behavior Seen As Individuals Age

At the April 1995 Society for Research in Child Development Meeting, Dr. Piven and his research group presented the results of their behavioral studies. They reviewed data on the current autistic behaviors in 38 high-functioning adolescent and adult autistic individuals and compared it to their behaviors at age 5 years. These researchers found that there was clear improvement in all three domains of behavior that define autism.However, the most substantial change occurred in the social and communication behaviors. Eighty percent of the males and one hundred percent of the females improved their social and communication skills. Both males and females had fifty percent improvement in ritualistic-repetitive behaviors. Dr. Piven and his colleagues are continuing their study of the course of behavioral change in autism.

Piven J., Harper J., Palmer P., and Arndt S. Course of behavioral change in autism: a retrospective study of high-IQ adolescents and adults. Journal of the American Academy of Child Adolescent Psychiatry 35:4, 523-29, 1996.

Center for Human Genetics Autism Research

To help us reach the goal of discovering the genetic, or inherited causes of autism, we collaborate with other researchers and medical centers. Our growing team now includes other experts in the fields of autism and genetic research. Our collaborators include Robert DeLong, MD of Duke University Medical Center, Dr.’s Ruth Abrahmson, Mike Curcarro and Harry Wright of the W.S. Hall Psychiatric Institute (Columbia, SC), Joseph Piven, MD at the University of Iowa (Iowa City, IA), Susan Folstein, MD at Tufts University (Boston, MA), Nina Sajaniemi, PhD at Helsinki University Central Hospitial (Helsinki, Finland), and their research groups.In order to find the genes for autism, we compare the genetic material (DNA) of individuals with autism to their family members without autism. We also compare genetic material between the families that have members with autism. The genetic material is obtained through blood samples. Once a family decides to join our study, we request all participating family members to give a blood sample. We also review family and medical history and conduct the Autism Diagnostic Interview (ADI) in order to confirm the diagnosis of the family member(s) with autism. However, families will not have to travel to Duke University Medical Center in order to participate. Instead, we try to visit the families personally to collect blood samples and diagnostic information. Family physicians may also collect the blood samples and mail the samples to us. The family history interview and ADI may be done as a telephone interview at any time convenient for the family. All information shared with the Center for Human Genetics is considered medical information and thus kept confidential. Since this is an ongoing research study to identify the genes associated with autism, there are no individual test results that we can report to participating families. However, we update the families participating in our study each year through our newsletter which explains our current findings and research progress.

This has been a productive year for the autism genetic research study. Over the past year we have had the privilege of working with more than 125 families. Sixty of these families have more than one family member with autism. We have enjoyed meeting these families and we look forward to working with them over the next few years.

Support Organizations

Autism Society of America (ASA)
7910 Woodmont Avenue, Suite 650
Bethesda, MD 20814
            (800) 3-AUTISM      
National Alliance for Autism Research (NAAR)
66 Witherspoon Street
Suite 310
Princeton, NJ 08542
            (888) 777-NAAR       (6227)

Center for Human Genetics Contact

Autism References

Unavailable at this time.

Autism Newsletter

Available through the mail. Please call             (800) 283-4316      

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