Small Steps Mark Progress In Understanding Autism

On July 19, parents of autistic children as well as professionals who work with such youngsters gathered in San Diego to greet three young men who had cycled across the United States to increase awareness of autism and to increase funding for autism research. As the cyclists pulled into their midst, they cheered, applauded, and whistled. A marine band played “God Bless America.”

The major reason the autism community had come together, however, was to attend a three-day conference sponsored by the Autism Society of America. They hoped to learn more about how to help children with autism on a day-by-day basis and especially to find out whether any medical research progress is being made against this disorder.

One message they heard was that while no major breakthroughs have been made, researchers have made some incremental progress in understanding the condition’s prevalence and causes.

The complex condition, conference speakers noted, involves core symptoms such as difficulty socializing, difficulty communicating, and ritualistic behaviors such as hand-flapping or repeatedly lining toys up in a row. But it can also include mental retardation, seizures, sleep problems, gastrointestinal troubles, inattention, hyperactivity, tics, and decreased response to pain yet excessive sensitivity to other sensory stimuli.

In other words, no two persons with autism have identical features of the disorder. One, for instance, may be profoundly impaired in hearing comprehension yet have visual understanding, whereas another may display the opposite.

Is autism truly increasing as many reports have indicated? Probably not, reported Judith Grether, Ph.D., a research scientist with the California Department of Health Services in Oakland. California has a Department of Developmental Services with 21 regional centers that diagnose children with autism and other developmental disorders. The department also keeps track of the prevalence of autism diagnoses over the years. So Grether and her colleagues decided to use the department’s database to determine how many children in California were diagnosed with autism or mental retardation without a known cause between 1987 and 1994.

They found that there had been an increase in the number of children diagnosed with autism between 1987 and 1994, yet during those years there had been a comparable decrease in the number of children diagnosed with mental retardation of no known cause. “So there was probably a shift in diagnosis during those years, not an increase in autism,” Grether and her team concluded.

The conference speakers also addressed theories of what causes autism. Might it be the measles-mumps-rubella vaccine? After all, some parents of children with autism suspect that the vaccine might be at fault, since their children’s autism symptoms started around the same time that the children received that vaccine, which is usually at 18 months of age. Yet evidence suggests that the vaccine is probably not a culprit, reported Eric Courchesne, Ph.D., director of the Research on the Neuroscience of Autism Laboratory at the University of California at San Diego. Grether agreed: “At this point there is not a credible connection, and I am talking about a number of studies.”

However, other investigations into this possibility are underway, Grether admitted. Courchesne said that some of these studies were being conducted by the National Institutes of Health in Bethesda, Md. Scientists are taking these studies very seriously, he said.

Evidence does continue to mount that genes play a major role in autism. For instance, if one identical twin has autism, the other has a 60 percent chance of also having it, reported Karin Nelson, M.D., a child neurologist and acting chief of the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke in Bethesda, Md.

Also, if parents already have one child with autism, their chances of having another with it are 3 percent to 5 percent greater than the general population’s risk of having a child with the condition, Nelson pointed out.

Nonetheless, getting a handle on the culprit gene or genes is turning out to be tougher than scientists anticipated. There are about six laboratories throughout the world that have been in hot pursuit of autism genes, including that of Donna Spiker, Ph.D. Spiker is clinical director of the Stanford Autism Genetics Project, which is part of the department of psychiatry at Stanford University School of Medicine. Yet while several promising locations for autism genes have been identified, for example on chromosome numbers 7 and 15, none of the results have been replicated across all of the study groups. So “there seem to be numerous genes with small effects,” Spiker said.

Also challenging researchers in pursuit of the causes of autism is the fact that so many areas of the brain can be affected by the condition—the frontal lobe, temporal lobe, parietal lobe, amygdala, hippocampus, and corpus callosum, for example. Yet one brain area—the cerebellum—does appear to be consistently affected in autism patients, reported Karen Pierce, Ph.D., a senior research scientist in Courchesne’s lab. This consistency may give researchers a tip on where to look for causes.

A new discovery by Nelson, Grether, and colleagues, however, may bring investigators even closer to the origins of autism than the cerebellum has.

They collected blood that had been taken from 246 subjects at birth and stored in a deep freezer. Of the 246 subjects, 69 had autism, 60 mental retardation, 63 cerebral palsy, and 54 were healthy controls. They then analyzed the blood samples for five different brain proteins—nerve growth factor, substance P, brain-derived neurotrophic factor, calcitonin gene–related peptide, and vasoactive intestinal peptide.

They found comparable amounts of nerve growth factor and substance P in blood samples from all four groups of subjects. However, they found much higher levels of the other three proteins in blood taken from subjects with autism and with mental retardation than in blood taken from the cerebral palsy subjects and healthy controls. And what was especially intriguing is that while about a quarter of the autism subjects did not develop symptoms of autism until they were at least 1 year old, they already had large amounts of these three proteins at birth.

Thus the three proteins may well play causative roles in autism, Nelson and her team concluded, and they believe their findings also suggest that autism is already present at birth or maybe even before. Some other evidence, in fact, also implies that this is the case, she pointed out.

For instance, if mouse-embryo brains are exposed to vasoactive intestinal peptide, they flourish; but if the brains are deprived of this protein, they do not grow properly. Vasoactive intestinal peptide is also known to be involved in the sleep-wake cycle, and autism patients often have sleep problems. Vasoactive intestinal peptide is also known to be made in the gut, and autism patients often have gastrointestinal problems.

Yet there is reason to believe that vasoactive intestinal peptide, brain-derived neurotrophic factor, and calcitonin gene–related peptide are not the only neurochemical culprits that may underlie autism, Nelson explained.

For instance, Elaine Perry, Ph.D., of Newcastle General Hospital in Newcastle-Upon-Tyne, England, and her collegues recently reported that nerve receptors for acetylcholine—so-called nicotinic receptors—are abnormal in the brains of deceased autism patients (Psychiatric News, July 20). Nelson called their discovery “exciting.” She also said that since brain-derived neurotrophic factor, vasoactive intestinal peptide, and calcitonin gene–related peptide are known to influence acetlcholine, it is quite possible that all are involved in the origin of autism.

“This is not an easy story; we are not going to have snappy solutions,” Nelson admitted. “But I think we are finally on the right track, and probably all of these discoveries are pieces of the puzzle, and the challenge will be to see how well they all fit together.”

Meanwhile, parents of children with autism are eagerly awaiting a cure. “There is hope, don’t give up!,” Miriam Jang, M.D., a family practitioner from San Rafael, Calif. advised one of the mothers attending the conference. Jang was in a good position to offer encouragement: In addition to being a physician and up on the latest in autism research, she has a child with autism. ▪