Antidepressants commonly prescribed to people with autistic spectrum disorders cannot be recommended based on current evidence, a new study by Cochrane Researchers concludes. Despite some evidence of benefits in adults diagnosed with autism, they say there is no evidence for any benefits associated with selective serotonin reuptake inhibitors (SSRIs) in children, who may suffer serious adverse effects as a result of taking the drugs.

Autistic spectrum disorders are difficult to treat because of the range of symptoms experienced by patients, including difficulties with social interactions and communication. SSRIs are among the most commonly prescribed medications, although none have been specifically approved by any drug authority for use in autism. In the UK, most antidepressants are not approved for children for any condition. The rationale behind the use of SSRIs in autism is that they act on serotonin, the same chemical in the body that is responsible for some of the psychological processes affected by the condition.

The researchers included a total of seven trials, involving 271 patients, in their study. The trials evaluated fluoxetine, fluvoxamine, fenfluramine and citalopram. Overall, the researchers found no benefit in the five trials in children and some evidence of serious harm, including one child who suffered a prolonged seizure after taking citalopram. The two trials in adults were very small and thus, although there was some evidence for improvement in symptoms, the authors concluded there was too little evidence for the drugs to be recommended. A major problem with analysing the results was that all the trials used different measures for assessing the drugs’ effects.

“We can’t recommend SSRIs as treatments for children, or adults, with autism at this time. However, decisions about the use of SSRIs for co-occurring obsessive-compulsive disorder, aggression, anxiety or depression in individuals with autism should be made on a case by case basis,” said lead author Katrina Williams of the School of Women’s and Children’s Health at the University of New South Wales & Sydney Children’s Hospital in Sydney, Australia.

“Not all the SSRIs currently in use have undergone controlled trials for autistic spectrum disorders, but parents are often anxious to try treatments regardless of the lack of evidence. It’s important that doctors are open about the lack of evidence, and explain any risks fully, before prescribing these treatments.”

Reference: Wiley-Blackwell, Autism: Lack of evidence for antidepressants, August 7, 2010

Related Articles:

1. Antidepressants Offer No Relief for Repetitive Behaviors in Children with Autism
2. Children with Autism show slower pupil responses, study finds
3. Autism – Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?
4. Neuroimaging: New insights in the pathophysiological mechanisms of Autism
5. A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity

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. 

Reference:

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

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. 

Reference:

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.

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.

Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. 

Reference: Verhoeven JS, De Cock P, Lagae L, Sunaert S., Neuroimaging of autism, Neuroradiology. 2009 Sep 15.

As we watched each of our five grandchildren and their friends enter this world and begin their life’s journey, it became more and more clear that something is amiss with this generation.  How are your children and your friend’s children doing?

In the United States, one of three of the children in this generation suffers from a chronic illness.  Perhaps it’s cancer, or birth defects, perhaps asthma, or a problem that affects the child’s mind and behavior, such as Downs Syndrome, learning disorders, ADHD or autism.  Though one in three may sound exaggerated, unbelievable, the figures are there amidst various government files.

This generation is different.  Childhood cancer, once a medical rarity, has grown 67 percent since 1950.  Asthma has increased 140 percent in the last twenty years and autism rates without a doubt have increased at least 200 percent.  Miscarriages and premature births are also on the rise, while the ratio of male babies dwindles and girls face endometriosis even in teenage.

The generations born from 1970 on are the first to be raised in a truly toxified world.  Even before conception and on into adulthood, the assault is everywhere: heavy metals and carcinogenic particles in air pollution; industrial solvents, household detergents, prozac and radioactive wastes in drinking water; pesticides in flea collars; artificial growth hormones in beef, arsenic in chicken; synthetic hormones in bottles, teething rings and medical devices; formaldehyde in cribs and nail polish, and even rocket fuel in lettuce.   Pacifiers are now manufactured with nanoparticles from silver, to be sold as “antibacterial.”  What’s wrong with rinsing a pacifier in soapy water?

Despite naysayers (who pays them to say nay? ”that’s a whole story in itself), it’s clear there is both an association and a causative connection between the vast explosion of poisons in our everyday lives and our children’s “issues.”  Over 80,000 industrial chemicals (tested only by the manufacturer) are in commerce in this country, produced or imported at 15 trillion pounds a year.   Pesticide use has leapt from the troubling 400 million pounds Rachel Carson wrote about in the 1960s to the mind-boggling 4.4 billion pounds in use today.   Nuclear power plants, aging and under-maintained, increasingly leak wastes, often without notifying their community.

What could be more elemental than our desire to protect our children.  Children and fetuses, because of their undeveloped defense systems, are ten to sixty-five times more susceptible to specific toxics than adults.  These toxics diminish the capacities of our children…the future of our families, our communities, our nation, and yours.

Illness does not necessarily show up in childhood.  Environmental exposures, from conception to early life, can set a person´s cellular code for life and can cause disease at any time, through old age. This accounts for the rise in Parkinson´s and Alzheimer´s diseases, prostate and breast cancer.

Yet this is not the dispiriting “Bad News” it might seem.  It is, actually, a message of hope and optimism.  We are fearful only when we are ignorant and powerless.  Now that we know what is happening, we can determine not to let it happen further.

These poisons are manmade; manufacturers can take them out of our children´s lives and make profits from safe products.  “Green chemistry” can replace toxic molecules with harmless ones.  We can connect global climate change actions to environmental health strategies.  If we replace coal-fired power, in the process we reduce not only carbon but also emissions of the tons of lead, mercury, hydrochloric acid, chromium, arsenic, sulfur and nitrogen oxides that cause autism, Alzheimer’s and other public health menaces.

We cannot bury our heads and hope it will all go away.  We cannot leave the job to someone else.  Some may feel the problem is so massive, it’s best to pretend it doesn’t exist.  But it isn’t more massive than we allow it to be.  It’s totally within our reach.

Here America, we look to Europe for ideas and strategies you have used, for the research coming out of your universities, for an understanding of the politics that enable your governments to pass strong environmental health laws.  The weed killer named atrazine in the U.S., made by Syngenta, a Swiss company, has never been approved for use in Europe.  But in the U.S., it is used on tens of millions of acres of farmland, on our lawns, gardens, parks, and golf courses.   Why?  And why has Europe begun screening chemicals under the REACH program, while industry in the U.S. has successfully opposed it?

Learning from each other, we can make each other smarter and stronger.  It is in our power to learn about what harms our children, to share our knowledge, and to demand action.

Author: Alice Shabecoff for CSN – Chemical Sensitivity Network, September 14, 2009

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Alice Shabecoff is the co-author with her husband Philip of Poisoned Profits: The Toxic Assault on our Children, published by Random House last year.  See their website, www.poisonedprofits.com.

 

Dental amalgams containing 50% mercury (Hg) have been used in dentistry for the last 150 years, and Hg exposure during key developmental periods was associated with autism spectrum disorders (ASDs).  

This study examined increased Hg exposure from maternal dental amalgams during pregnancy among 100 qualifying participants born between 1990 -1999 and diagnosed with DSM-IV autism (severe) or ASD (mild). Logistic regression analysis (age, gender, race, and region of residency adjusted) by quintile of maternal dental amalgams during pregnancy revealed the ratio of autism: ASD (severe: mild) were about 1 (no effect) for </=5 amalgams and increased for>=6 amalgams. Subjects with>=6 amalgams were 3.2-fold significantly more likely to be diagnosed with autism (severe) in comparison to ASD (mild) than subjects with </=5 amalgams.  

Dental amalgam policies should consider Hg exposure in women before and during the child-bearing age and the possibility of subsequent fetal exposure and adverse outcomes. 

Literature: Geier DA, Kern JK, Geier MR., A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity, Acta Neurobiol Exp (Wars). 2009;69(2):189-97. 

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