Children With Autism Show Slower Pupil Responses, Study Finds

Pupil-Test new Biomarker for Autism?


Autism affects an estimated 1 in 150 children today, making it more common than childhood cancer, juvenile diabetes and pediatric AIDS combined. Despite its widespread effect, autism is not well understood and there are no objective medical tests to diagnose it. Recently, University of Missouri researchers have developed a pupil response test that is 92.5 percent accurate in separating children with autism from those with typical development. In the study, MU scientists found that children with autism have slower pupil responses to light change. 

“No comprehensive study has been conducted previously to evaluate the pupils’ responses to light change, or PLR, in children with autism,” said Gang Yao, associate professor of biological engineering in the MU College of Agriculture, Food and Natural Resources and the College of Engineering. “In this study, we used a short light stimulus to induce pupil light reflexes in children under both dark and bright conditions. We found that children with autism showed significant differences in several PLR parameters compared to those with typical development.” 

In the study, scientists used a computerized binocular infrared device, which eye doctors normally use for vision tests, to measure how pupils react to a 100-millisecond flash light. A pupil reaction test reveals potential neurological disorders in areas of the brain that autism might affect. The results showed that pupils of children diagnosed with autism were significantly slower to respond than those of a control group. 

“There are several potential mechanisms currently under study,” Yao said. “If these results are successfully validated in a larger population, PLR response might be developed into a biomarker that could have clinical implications in early screening for risks of autism. Studies have shown that early intervention will improve these children’s developmental outcome.” 

Yao’s study, completed with Xiaofei Fan, post-doctoral fellow at MU, Judith Miles, professor and William S. Thompson Endowed Chair in Child Health, and Nicole Takahashi, senior research specialist at MU’s Thompson Center for Autism and Neurological Disorders, has been published in the Journal of Autism and Developmental Disorders. In October, the scientists received a grant from the National Institutes of Health for the next phase. For this study, the researchers hope to amplify the earlier study’s measurements and investigate any correlation between PLR and several other medical conditions that could be associated with autism. 



Xiaofei Fan, Judith H. Miles, Nicole Takahashi and Gang Yao. Abnormal Transient Pupillary Light Reflex in Individuals with Autism Spectrum Disorders. Journal of Autism and Developmental Disorders, 2009; 39 (11): 1499 DOI: 10.1007/s10803-009-0767-7 

Adapted from materials provided by University of Missouri-Columbia, via EurekAlert! Nov. 11, 2009

Picture: University of Missouri

Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children

Children with learning disabilityAmong dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. 

Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. 

Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. 

Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination.

Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body. 


Dufault R, Schnoll R, Lukiw WJ, Leblanc B, Cornett C, Patrick L, Wallinga D, Gilbert SG, Crider R., Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children, Behav. Brain Funct. 2009 Oct 27;5(1):44.

Autism – Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?

Autism - Cute little Boy living in his own world

Increased prevalence of the autism spectrum disorders (ASD) and the failure to find genetic explanations has pushed the hunt for environmental causes. These disorders are defined clinically but lack objective characterization.

 To meet this need, we measured neurobehavioral and pulmonary functions in eight ASD boys aged 8 to 19 years diagnosed clinically and compared them to 145 unaffected children from a community with no known chemical exposures. As 6 of 35 consecutive mold/ mycotoxin (mold)-exposed children aged 5 to 13 years had ASD, we compared them to the 29 non-ASD mold-exposed children, and to the eight ASD boys. Comparisons were adjusted for age, height, weight, and grade attained in school. 

The eight ASD boys averaged 6.8 abnormalities compared to 1.0 in community control boys. The six mold-exposed ASD children averaged 12.2 abnormalities. The most frequent abnormality in both groups was balance, followed by visual field quadrants, and then prolonged blink reflex latency. 

Neuropsychological abnormalities were more frequent in mold-exposed than in terbutaline-exposed children and included digit symbol substitution, peg placement, fingertip number writing errors, and picture completion. Profile of mood status scores averaged 26.8 in terbutaline-exposed, 52 in mold exposed, and 26 in unexposed. The mean frequencies of 35 symptoms were 4.7 in terbutaline, 5.4 in mold/ mycotoxins exposed and 1.7 in community controls. 

Reference:   Kilburn KH, Thrasher JD, Immers NB., Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?, Toxicol Ind Health. 2009 Sep 30.

Antidepressants Offer No Relief for Repetitive Behaviors in Children with Autism

The repetitive behaviors exhibited by some children and teens with autism spectrum disorders are not reduced with the antidepressant citalopram, according to a study in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals. Lawrence Scahill, professor at Yale University School of Nursing and the Child Study Center was the principal investigator at Yale for the multi-center study. Yale Child Study Center Director Fred R. Volkmar, M.D., authored an accompanying editorial.

Repetitive behaviors in children with autism – including inflexible routines and repetitive play – tend to persist over time and often interfere with everyday life. The United States Food and Drug Administration has not approved any drugs to treat the core symptoms of autism and related disorders, but medications like citalopram are increasingly being used in these populations, the authors write.

Citalopram is in the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), which alter how the brain regulates the neurotransmitter serotonin. Scahill said that citalopram has been prescribed because of similarities between the repetitive behavior of autism spectrum disorders and that of obsessive-compulsive disorder. There is also some evidence suggesting that there may be abnormalities of the serotonin system in autism. Because the SSRIs work for adults and children with obsessive-compulsive disorder, he noted, some believed it could also be adapted for use in children with autism.

“Despite the limited evidence supporting their use in children with autism, SSRIs are among the most frequently used medications in this population. This is due in part because of their perceived safety,” said Scahill.

Scahill, along with colleagues at various institutions conducted a randomized controlled trial to determine the safety and efficacy of citalopram in children with autism spectrum disorders who had at least moderate levels of repetitive behavior. Of 149 children age 5 to 17 who participated, 73 were randomly assigned to receive citalopram and 76 received a placebo for 12 weeks.

At the end of the treatment period, there were no differences between the citalopram group and the placebo group in percentage of children showing overall improvement or on scales measuring repetitive behavior. Indeed, noted the researchers, citalopram was more likely than placebo to be associated with adverse events, such as hyperactivity, insomnia, impulsiveness, decreased concentration, stereotypy (abnormal repetitive movements), diarrhea and dry skin.

“These results highlight the importance of placebo-controlled trials of medications commonly used for children with autism spectrum disorders to determine whether risks of medications outweigh benefits,” said Scahill.

In the accompanying editorial on the study, Yale Child Study Center Director Fred R. Volkmar, M.D., said the data might change the practice of prescribing SSRIs to children with autism.

“Previous double-blind, placebo-controlled studies with SSRIs in adults with autism showed a reduction in levels of repetitive behaviors,” Volkmar writes. “Given the frequency of such behaviors in children with autism and their association with other features such as anxiety, depression and rigidity, selective serotonin reuptake inhibitors would seem to have, at the least in theory, some therapeutic potential.”

Volkmar added, “Although the findings in the study were negative, the results are not difficult to interpret. The medication does not appear to be useful for repetitive behaviors in children with autism and related conditions. We need more studies of this kind to advance research and guide clinical practice.”

The National Institutes of Health via STAART center contracts funded the study. The work was also funded in part by a Clinical and Translational Science Award (CTSA) from the National Center for Research Resources at the National Institutes of Health.

Other authors on the study include first author Bryan H. King, M.D., Eric Hollander, M.D., Linmarie Sikich, M.D., James T. McCracken, M.D., Joel D. Bregman, M.D., Craig L. Donnelly, M.D., Evdokia Anagnostou, M.D., Kimberly Dukes, Lisa Sullivan, Deborah Hirtz, M.D, Ann Wagner, and Louise Ritz.

Citation: Arch Gen Psychiatry Vol. 66 (no. 6) 492 (June 2009).

Reference: Yale, Antidepressants Offer No Relief for Repetitive Behaviors in Children with Autism, Press Release, June 1. 2009