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

Paris, France – June 04, 2009 – The cause of Parkinson’s disease (PD), the second most frequent neurodegenerative disease after Alzheimer’s disease, is unknown, but in most cases it is believed to involve a combination of environmental risk factors and genetic susceptibility. Laboratory studies in rats have shown that injecting the insecticide rotenone leads to an animal model of PD and several epidemiological studies have shown an association between pesticides and PD, but most have not identified specific pesticides or studied the amount of exposure relating to the association.  

A new epidemiological study involving the exposure of French farm workers to pesticides found that professional exposure is associated with PD, especially for organochlorine insecticides. The study is published in Annals of Neurology, the official journal of the American Neurological Association.  

Led by Alexis Elbaz M.D., Ph.D., of Inserm, the national French institute for health research in Paris, and University Pierre et Marie Curie (UPMC, Paris 6), the study involved individuals affiliated with the French health insurance organization for agricultural workers who were frequently exposed to pesticides in the course of their work. Occupational health physicians constructed a detailed lifetime exposure history to pesticides by interviewing participants, visiting farms, and collecting a large amount of data on pesticide exposure. These included farm size, type of crops, animal breeding, which pesticides were used, time period of use, frequency and duration of exposure per year, and spraying method. 

The study found that PD patients had been exposed to pesticides through their work more frequently and for a greater number of years/hours than those without PD. Among the three main classes of pesticides (insecticides, herbicides, fungicides), researchers found the largest difference for insecticides: men who had used insecticides had a two-fold increase in the risk of PD. 

“Our findings support the hypothesis that environmental risk factors such as professional pesticide exposure may lead to neurodegeneration,” notes Dr. Elbaz.  

The study highlights the need to educate workers applying pesticides as to how these products should be used and the importance of promoting and encouraging the use of protective devices. In addition to the significance of the study for those with a high level of exposure to pesticides, it also raises the question about the role of lower-level environmental exposure through air, water and food, and additional studies are needed to address this question.  

Reference: Alexis Elbaz, Jacqueline Clavel, Paul J. Rathouz, PhD 6, Frédéric Moisan Jean-Philippe Galanaud, Bernard Delemotte, Annick Alpérovitch, Christophe Tzourio, Professional exposure to pesticides and Parkinson’s disease, Annals of Neurology, Press Release Wiley Blackwell, June 4, 2009

Estrogen-like endocrine disrupting chemicals (EEDC) are exogenous, man-made chemicals that alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding or cellular responses of natural estrogens.  

EEDCs have been found in various plastic products, flame retardants, pesticides and many other products that are needed for daily use. Some of the greatest effects of EEDCs are on puberty, a period of rapid physiological changes like growth spurt, maturation of the gonads and the brain.  

Estrogen, one of the key hormones required in puberty is crucial for the sexual differentiation. The structural similarity of estrogen disruptors with estrogen allow them to bind and activate estrogen receptors and show a similar response even in the absence of estrogen that can lead to precocious puberty (PP).  

Major EEDCs found abundantly in our environment include; dichlorodiphenyltrichloroethane (DDT), dioxin, polychlorinated biphenyls (PCBs), bisphenol A (BPA), polybrominated biphenyls (PBB), phthalate esters, endosulfan, atrazine and zeranol.  

In girls, DDT has been linked to earlier menarche. Dioxin causes abnormal breast development in pre-pubertal girls. BPA has shown to cause PP in pubertal girls. PBB causes earlier menarche, thelarche and earlier pubic hair stage in pubertal girls. PCB’s showed a significant delay in puberty in pubertal boys. De-feminization, thelarche, or early secondary breast development are shown in pubertal girls when exposed to phthalate esters. Endosulfan affects pubertal boys by slowing down the timing of reproductive maturation.

This article provides a possible structure-function relation of the above mentioned EEDCs which interfere with sexual development during puberty.

Reference: Roy JR, Chakraborty S, Chakraborty TR., Estrogen-like endocrine disrupting chemicals affecting puberty in humans – a review, Department of Biology, Adelphi University, Garden City, New York, NY, U.S.A., Med Sci Monit. 2009 Jun;15(6):RA137-145.

Pyrethrin and Pyrethroide insecticides are commonly applied in homes and businesses and on some agricultural crops. This research used a two-state regional approach to analyze reports of acute pesticide poisonings due to Pyrethrin and Pyrethroide insecticides.  

The Washington State Department of Health and the Oregon Public Health Division collected pesticide poisoning surveillance data from 2001 through 2005. Cases were included if they involved exposure to at least one Pyrethrin or Pyrethroide insecticide. Descriptive statistics were calculated; differences between categories were assessed using Chi-square analysis.  

A total of 407 cases fit our definition. Overall, the rate of poisoning in Oregon was significantly higher than in Washington (incidence rate ratio 1.70, 95% confidence interval 1.40, 2.07), and rates for both states generally increased during the time period. For both states, most exposures resulted in low severity illnesses (92%), and most were classified as possible cases (73%). Only about one-fourth of cases were related to a person’s work. The most common category of clinical signs and symptoms of illness was respiratory (52% of cases), followed by neurological (40% of cases). Exposure route was predominantly inhalation; there was no association between route and case severity. There was a significant association between illness severity and losing time from work or regular activities (p<0.0001).  

Although the majority of Pyrethrin and Pyrethroide poisoning cases were low in severity, adverse reactions have occurred, as transpired in Oregon in 2005. Regional analysis has the potential to improve the surveillance system and provide unique opportunities for targeting preventive interventions. 

Reference:

Walters JK, Boswell LE, Green MK, Heumann MA, Karam LE, Morrissey BF, Waltz JE., Pyrethrin and Pyrethroide illnesses in the Pacific Northwest: a five-year review, Oregon Department of Human Services, Public Health Division, Office of Environmental Public Health, Toxicology, Assessment, & Tracking Services, Oregon Worker Illness and Injury Prevention Program, Portland, OR 97232, USA, Public Health Rep. 2009 Jan-Feb;124(1):149-59.

Researchers at the Johns Hopkins University School of Medicine have found that a chemical commonly used in the production of such medical plastic devices as intravenous (IV) bags and catheters can impair heart function in rats. Reporting online this week in the American Journal of Physiology, these new findings suggest a possible new reason for some of the common side effects—loss of taste, short term memory loss–of medical procedures that require blood to be circulated through plastic tubing outside the body, such as heart bypass surgery or kidney dialysis. These new findings also have strong implications for the future of medical plastics manufacturing.

In addition to loss of taste and memory, coronary bypass patients often complain of swelling and fatigue. These usually resolve within a few months after surgery, but they are troubling, sometimes hinder recovery, but generally go away.

His personal experience with coronary bypass surgery propelled his search for a root cause for the loss of taste phenomenon, reports principal investigator Artin Shoukas, Ph.D., professor of biomedical engineering, physiology and anesthesiology and critical care medicine at Johns Hopkins. “I’m a chocoholic, and after my bypass surgery everything tasted awful, and chocolate tasted like charcoal for months.”

Shoukas and Caitlin Thompson-Torgerson, PhD, a postdoctoral fellow in anesthesiology and critical care medicine suspected the trigger for these side effects might be a chemical compound of some kind.

To test their theory, Shoukas and his team of researchers took liquid samples from IV bags and bypass machines before they were used on patients. The team analyzed the fluids in another machine that can identify unknown chemicals and found the liquid to contain a chemical compound called cyclohexanone. The researchers thought that the cyclohexanone in the fluid samples might have leached from the plastic. Although the amount of cyclohexanone leaching from these devices varied greatly, all fluid samples contained at least some detectable level of the chemical.

The researchers then injected rats with either a salt solution or a salt solution containing cyclohexanone and measured heart function. Rats that got only salt solution pumped approximately 200 microliters of blood per heartbeat and had an average heart rate of 358 beats per minute, while rats injected with cyclohexanone pumped only about 150 microliters of blood per heartbeat with an average heart rate of 287 beats per minute.

In addition to pumping less blood more slowly, rats injected with cyclohexanone had weaker heart contractions. The team calculated that cyclohexanone caused a 50 percent reduction in the strength of each heart contraction. They also found that the reflex that helps control and maintain blood pressure is much less sensitive after cyclohexanone exposure. Finally, the team observed increased fluid retention and swelling in the rats after cyclohexanone injections.

According to Thompson-Torgerson and Shoukas, they would like to figure out how these side effects—decreased heart function and swelling—occur and to what degree cyclohexanone is involved. Despite the findings in this study, they emphasize that patients should listen carefully to the advice of their physicians. “We would never recommend that patients decline this type of treatment if they need it,” says Shoukas. “On the contrary, such technologies are life-saving medical advances, and their benefits still far outweigh the risks of the associated side effects. As scientists, we are simply trying to understand how the side effects are triggered and what the best method will be to mitigate, and ultimately remedy, these morbidities.”

Authors on the paper are Caitlin S. Thompson-Torgerson, Hunter C. Champion, Lakshmi Santhanam, Z. Leah Harris and Artin A. Shoukas, all of Johns Hopkins University School of Medicine.

Reference:
Johns Hopkins, Chemical found in medical devices impairs heart function, Press Release, May 1, 2009