Do Psychiatric Medications in Water Contribute to Autism?

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Prozac-Contaminated Drinking Water May Be Link To Autism

By Drew Armstrong - Jun 6, 2012 5:00 PM ET

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Fish exposed to psychiatric medicines in water showed gene patterns similar to those found in people with autism, in a study suggesting a link between drugs that get into the human drinking supply and the disease.

Researchers put antidepressants Prozac and Effexor, as well as antiseizure drug Tegratol into water tanks of minnows. Tests showed that the same genes turned on in people with autism were also triggered in the fish after exposure, according to a study published today in the journal PLoS ONE.

The findings suggest that small amounts of psychiatric medications found in the drinking supply may be a cause of autism, the researchers said. Psychiatric drugs have been linked to autism-like symptoms in studies of rats exposed to the medicines, according to the study.

“An environmental cause is really not on the radar for a lot of people,” said study author Michael Thomas, a professor of evolutionary biology at Idaho State University in Pocatello, in a telephone interview. “My sincere hope is that this opens the door to a new question and allows people to look into that possibility.”

Concentrations of the drugs are found downstream from water treatment plants that process human waste that contains the medicines, Thomas said. The molecules make their way into the supply downstream, where pregnant mothers who drink the water can pass the exposure to their fetuses.

“While others have envisioned a causal role for psychotropic drugs in idiopathic autism, we were astonished to find evidence that this might occur at very low dosages, such as those found in aquatic systems,” Thomas said in a statement accompanying the study.

Eli Lilly & Co.’s Prozac, Pfizer Inc.’s Effexor and their generic equivalents belong to classes of drugs that generated $14.2 billion in U.S. sales last year, according to data compiled by Wolters Kluwer NV and Bloomberg.

Higher Concentrations

The researchers used concentrations of the drugs higher than are measured in the field, which Thomas said was intentional.

“Every study that comes out that measures concentrations in the environment shows orders of magnitude higher than the previous study, so we figured the concentrations would catch up with us,” Thomas said.

The researchers are collecting water samples from places with known concentrations, and plan to test minnows in that water, he said.

Autism Rise

The number of children with autism and related disorders is rising, according to data collected by the U.S. Centers for Disease Control and Prevention in Atlanta. The number of 8-year- olds identified with autism spectrum disorders rose 23 percent in 2008 from 2006, according to a March CDC report. Some of the increase is due to a higher awareness of autism as a cause of behavioral disorders, though how much that contributed to the rise isn’t known, according to the report.

Autism includes a range of disorders characterized by social impairment, communication difficulties, and restricted, repetitive patterns of behavior, according to the National Institutes of Health.

The study was supported by funding from the PhRMA Foundation, National Institutes of Health and Idaho State University.

To contact the reporter on this story: Drew Armstrong in New York atdarmstrong17@bloomberg.net;

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

More Information on NAC for Irritability

Here is another article on NAC. This one is from PsychCentral. 

By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on May 30, 2012

A new pilot study suggests a specific antioxidant supplement may be an effective therapy for some features ofautism.
Researchers from the Stanford University School of Medicine and Lucile Packard Children’s Hospital studied 31 children with the disorder.
The antioxidant, called N-Acetylcysteine, or NAC, effectively reduced irritability in children with autism and moderated repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial before NAC can be recommended for children with autism.
Irritability affects 60 to 70 percent of children with autism. “We’re not talking about mild things: This is throwing, kicking, hitting, the child needing to be restrained,” said Antonio Hardan, M.D., the primary author of the new study.
“It can affect learning, vocational activities and the child’s ability to participate in autism therapies.”
The study will appear in a forthcoming issue of the journal Biological Psychiatry.
Stanford University is filing a patent for the use of NAC in autism, and one of the study authors has a financial stake in a company that makes and sells the NAC used in the trial.
The dramatic increase in diagnosed cases of autistic spectrum disorders has made the discovery of new medications to treat autism and its symptoms a high priority for researchers.
Currently, irritability, mood swings and aggression, all of which are considered associated features of autism, are treated with second-generation antipsychotics.
However, these drugs can cause significant side effects, including weight gain, involuntary motor movements and metabolic syndrome, which increase diabetes risk.
By contrast, side effects of NAC are generally mild, with gastrointestinal problems such as constipation, nausea, diarrhea and decreased appetite being the most common.
The state of drug treatments for autism’s core features, such as social deficits, language impairment and repetitive behaviors, is also a major problem.
“Today, in 2012, we have no effective medication to treat repetitive behavior such as hand flapping or any other core features of autism,” Hardan said.
NAC could be the first medication available to treat repetitive behavior in autism — if the findings hold up when scrutinized further.
The study tested children with autism ages 3 to 12. They were physically healthy and were not planning any changes in their established autism treatments during the trial.
In a double-blind study design, children received NAC or a placebo for 12 weeks. The NAC used was a pharmaceutical-grade preparation donated by the neutraceutical manufacturer BioAdvantex Pharma.
Subjects were evaluated before the trial began and every four weeks during the study using several standardized surveys that measure problem behaviors, social behaviors, autistic preoccupations and drug side effects.
During the 12-week trial, NAC treatment decreased irritability scores from 13.1 to 7.2 on the Aberrant Behavior Checklist, a widely used clinical scale for assessing irritability. The change is not as large as that seen in children taking antipsychotics. “But this is still a potentially valuable tool to have before jumping on these big guns,” Hardan said.
In addition to the behavioral improvements, two standardized measures of autism mannerisms and stereotypic behavior showed that children taking NAC demonstrated a decrease in repetitive and stereotyped behaviors.
“One of the reasons I wanted to do this trial was that NAC is being used by community practitioners who focus on alternative, non-traditional therapies,” Hardan said. “But there is no strong scientific evidence to support these interventions. Somebody needs to look at them.”
Hardan cautioned that the NAC for sale as a dietary supplement at drugstores and grocery stores differs in some important respects from the individually packaged doses of pharmaceutical-grade NAC used in the study, and that the over-the-counter version may not produce the same results.
“When you open the bottle from the drugstore and expose the pills to air and sunlight, it gets oxidized and becomes less effective,” he said.
While researchers did not study the mechanisms by which NAC may work, two physiological hypotheses may explain the positive results.
In one scenario, NAC increases the capacity of the body’s main antioxidant network, which some previous studies have suggested is deficient in autism.
Another possibility embraces research that suggests autism is related to an imbalance in excitatory and inhibitory neurotransmitters in the brain. NAC is known to modulate the glutamatergic family of excitatory neurotransmitters – potentially balancing neurotransmitter levels and reducing the presentation of some autistic symptoms.
The scientists are now applying for funding to conduct a large, multicenter trial in which they hope to replicate their findings.
“This was a pilot study,” Hardan said. “Final conclusions cannot be made before we do a larger trial.”
Source: Stanford University

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NAC for Irritability symptoms of Autism

Here is an interesting treatment option to discuss with your healthcare provider, however, after reading you should review the side-effects and drug interactions at webmd; http://www.webmd.com/vitamins-supplements/ingredientmono-1018-N-ACETYL%20CYSTEINE.aspx?activeIngredientId=1018&activeIngredientName=N-ACETYL%20CYSTEINE before you run out to GNC and buy some for your child. This substance is easily obtained without a prescription, so it is important to know the good and the bad possibilities of use.

Contact: Rhiannon Bugno
biol.psych@utsouthwestern.edu
214-648-0880
Elsevier 

New treatment for irritability in autism

A new study in Biological Psychiatry reports

Philadelphia, PA, May 31, 2012 – Autism is a developmental disorder that affects social and communication skills. Irritability is a symptom of autism that can complicate adjustment at home and other settings, and can manifest itself in aggression, tantrums, and self-injurious behavior. These disruptive behaviors are frequently observed in children with autism, which may considerably affect their ability to function at home or in school.

N-acetylcysteine (NAC) is approved by the US Food and Drug Administration for the treatment of acetaminophen (Tylenol) overdoses, but it may have other applications related to its effects in the brain. NAC helps maintain and restore glutathione, which play a key role in the antioxidant defense system. Additionally, cysteine as supplied by NAC treatment, stimulates a protein, the cystine-glutamate antiporter, resulting in the decrease of glutamatergic neurotransmission. NAC has two resulting effects: 1) it may protect brain cells by raising the level of a protective antioxidant metabolite called glutathione, and 2) it may reduce the excitability of the glutamate system by stimulating inhibitory receptors.

These drug actions are important because, although the causes of autism are unknown, it is clear that there are many influencing factors and scientists are pursuing multiple hypotheses. Two in particular relate to NAC: one theory is that autism may be caused by an imbalance between oxidants and antioxidants in the body; the other is that the glutamate system may be dysfunctional in individuals with autism.

These hypotheses led researchers at Stanford University and the Cleveland Clinic to conduct a pilot trial of NAC in children with autistic disorder. Children were randomized to receive either NAC or placebo daily for 12 weeks and their symptoms were evaluated four times during that period.

They found that irritability was significantly decreased in the children who received NAC. In addition, NAC was well-tolerated and caused minimal side effects.

Lead author Dr. Antonio Hardan commented, "Data from this preliminary trial suggest that NAC has the potential to be helpful in targeting irritability in children with autism. It is also unclear if NAC improves other symptom domains in autism."

"At this point it is too early to tell how NAC reduced irritability in autism, but this finding will be an important addition to the field if it can be replicated," said Dr. John Krystal, Editor of Biological Psychiatry, where the study is being published.

Dr. Hardan agreed, adding that "large randomized controlled trials are needed to attempt to replicate the findings from this pilot trial and to determine whether or not NAC is effective in targeting other symptoms observed in autism such as repetitive and restricted interests." This small pilot study was the first step and so the next stages of work can now begin to determine whether NAC could potentially become an approved treatment for autism.

###

The article is "A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism" by Antonio Y. Hardan, Lawrence K. Fung, Robin A. Libove, Tetyana V. Obukhanych, Surekha Nair, Leonore A. Herzenberg, Thomas W. Frazier, and Rabindra Tirouvanziam (doi: 10.1016/j.biopsych.2012.01.014). The article appears in Biological Psychiatry, Volume 71, Issue 11 (June 1, 2012), published by Elsevier.

Notes for editors

Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Antonio Hardan at +1 650 723 5511 or hardanay@stanford.edu.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 4th out of 126 Psychiatry titles and 15th out of 237 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2010 Impact Factor score for Biological Psychiatry is 8.674.

About Elsevier

Elsevier is a world-leading provider of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including The Lancetand Cell, and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier's online solutions include SciVerse ScienceDirect, SciVerse Scopus, Reaxys, MD Consult and Mosby's Nursing Suite, which enhance the productivity of science and health professionals, and the SciVal suite and MEDai's Pinpoint Review, which help research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC, a world-leading publisher and information provider, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Media contact
Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
biol.psych@utsouthwestern.edu

Drug Trial on Arbaclofen for Autism

To read an MSNBC article about the trials of Arbaclofen for reduction of autism symptoms, copy and paste this URL;http://www.msnbc.msn.com/id/47630513/ns/health-mental_health/#.T8zqZbDOy5I

Here is a short passage from that article:

 "As Jack's experience suggests, that may be about to change. Researchers are conducting advanced trials of the first drugs expressly designed to correct the genetically induced signaling problems in the brain that result in autism. The early indications are positive enough to offer new hope for families and spark interest from drug companies. For patients, this research "may not solve their autism, but it may solve aggression, it may solve sensory overload, which leads to a lot of behavioral issues," says Isaac Pessah, an autism researcher at the University of California at Davis, who has not been involved in any of the drug trials."

According to the article the drug is still being studied in small trials and access by those not enrolled in these studies is still years away. 

Leaving Town

It is time for my husband and I to get away, leaving V at home with her caregivers. Well in advance, I post overnight shift opportunities for her usual daytime staff. I keep a file on my computer of documents I will update and print out each time we go out of town. These include a form that gives my written permission for support staff to authorize emergency medical treatment in my absence, with hospital preferences. I leave printed instructions regarding meals and appointments for V and check her medications to make sure that there is enough to last until I return. Usually this involves a trip to the pharmacy to refill something before I go. There are grocery shopping trips to make sure that I leave enough fresh and frozen food for all of her meals and snacks to last until I return. I check the dash of the vehicle that will be used in our absence and make sure it doesn't need oil and the battery has a strong charge. The last time I went out of town for an overnight, the car battery died in a park, requiring the staff to get a jump start from Park Police. Yikes!
Well, there is so much to do and worry about before I leave home that I almost need the vacation by the time I go. I exchange phone calls and texts with the staff each day to see how things went and to answer any questions that come up. Her routines continue without me. This makes my absence easier on her. This is how she is part of the family but lives her own life, while I have my independence too. I won't always be with her, so it is good that she can be okay away from me for a week now and then. I will tell her I am going away today and I will say goodbye tomorrow before I go. She won't like it, but she will be okay until I return. 

Dynavox Maestro - Seven months later

When the Dynavox representative came out for the training, the most valuable item she provided was a programming cheat sheet. It made it very easy and quick for our speech therapist and I to program the Maestro in the way that we wanted to for V.
At first, V did not want to use the device for lessons, but understood that the purpose of the device was to communicate. She started using it right away to choose what to eat for breakfast. Then she began to use it to indicate where she wanted to go in the community, and more specifically, what she wanted to do at that location. For example, if she chooses the library as her destination, she can indicate if she wants to look for a movie, a book or look at magazines. She tells us if she would rather go to Chick-fil-A or Chipotle Grill for lunch and then she indicates her preferred menu items with the device. At home she can choose her leisure activity with the Maestro or tell us that she wants to rest.
We have to do a lot of modeling to encourage her to use the device as opposed to the gestures or actions she has used in the past to indicate her preferences. However, the speech therapist said that she learned to navigate around the pages in the device to find what she wants to say much more quickly than she had anticipated. V had learned as much in two months with the Maestro as the SLP had expected her to learn in a year!
As V masters the choices that have been programmed for her, we continue to add to her choices and to allow the complexity of her communications to grow. She is now willing to use the device during speech sessions with her therapist.
I am very happy with V's progress on the Dynavox Maestro. It has given her the ability to express her wishes in ways that she was never able to do before. I look forward to the time that she is able to better express her feelings with the device, both physical and emotional. 

Bone Marrow Transplant as Treatment for Rett Syndrome

Here is a new approach to treating an autism spectrum disorder that I have not heard of before. It will be interesting to see how broad the implications are for treatment of other ASD's as the research progresses. Bone Marrow Transplant Arrests Symptoms in Model of Rett Syndrome ScienceDaily (Mar. 18, 2012) — A paper published online March 18 in Nature describes the results of using bone marrow transplant (BMT) to replace faulty immune system cells in models of Rett Syndrome. The procedure arrested many severe symptoms of the childhood disorder, including abnormal breathing and movement, and significantly extended the lifespan of Rett mouse models. Exploring the function of microglia deficient in methyl-CpG binding protein 2 (Mecp2), the protein encoded by the "Rett gene," principal investigator Jonathan Kipnis, Ph.D. and his team at the University of Virginia School of Medicine uncovered a completely novel approach to this devastating neurological syndrome. The work was funded by the Rett Syndrome Research Trust and the Rett Syndrome Research Trust UK. See Also: Health & Medicine Leukemia Osteoporosis Children's Health Immune System Stem Cells Chronic Illness Reference Rett syndrome Autistic spectrum Sex linkage Autism Rett Syndrome, the most physically disabling of the autism spectrum disorders, is caused by random mutations in the gene MECP2. Predominantly affecting girls, symptoms usually manifest between 6 and 18 months of age, when a frightening regression begins. Children lose acquired language skills and functional hand use; movement deteriorates as other Rett symptoms appear. These may include disordered breathing, Parkinsonian tremors, severe anxiety, seizures, digestive and circulatory problems and a range of autonomic nervous system and orthopedic abnormalities Although most children survive to adulthood, many are wheelchair-bound, rely on feeding tubes, are unable to communicate and require total, lifelong care. Kipnis was drawn to Rett Syndrome from his perspective as a neuroimmunologist. "What began as intellectual curiosity," he explains, "has become an intense personal commitment to studying the correlation between neurological function and the immune system in Rett Syndrome. The impact of BMT on so many different symptoms has triggered a flood of experiments we are now pursuing at full speed." The brain is largely composed of several types of glial cells, which have diverse and complex functions that include sustaining a healthy environment for neuronal growth and maintenance. Microglia are small glial cells that participate in the brain's immune response. One of their roles is to clean up normal cellular debris in the brain through the process of phagocytosis. Kipnis and his team discovered that when microglia lack properly functioning Mecp2, they are unable to perform this crucial duty efficiently. Because microglia are derived from immune progenitor cells, it is possible to replace them via a bone marrow transplant. First author Noël Derecki and his colleagues began their work with male Rett mouse models, which lack any Mecp2. These Mecp2-null mice mimic the human disorder, with neurological symptoms beginning to appear at about 4 weeks of age and an approximate life expectancy of only 8 weeks. Radiation treatment was administered at 4 weeks, followed by a bone marrow transplant from normal (wild-type) mice. As engraftment -- the migration and repopulation of new microglia -- took place, the Rett mice began to grow instead of fail. Body and brain sizes approached those of wild-type mice, gait improved and mobility increased significantly. There were no signs of the severe tremors seen in untreated mice. Apneas and other breathing irregularities were markedly diminished. The oldest of these mice is now almost a year. Work with female Rett mouse models at more advanced stages of disease is currently underway. Gail Mandel, Ph.D., whose Rett research focuses on astrocytes, another type of glial cell impaired by mutations in MECP2, comments, "A fascinating aspect of these findings is the data suggesting that deficits in the engulfing properties of microglia are a crucial aspect of Rett neuropathology. It will now be necessary to develop cellular assays to determine all the ways these immune cells are bolstering neuronal functions and whether they can be therapeutically harnessed." Dr. Mandel is a Senior Scientist at the Vollum Institute and a Professor in the Department of Biochemistry and Molecular Biology in the School of Medicine at Oregon Health & Science University and an Investigator of the Howard Hughes Medical Institute. Monica Coenraads, Executive Director of the Rett Syndrome Research Trust added, "I've been in almost daily contact with Dr. Kipnis since he brought his very original proposal to RSRT, and have been amazed to see the development of this brutal disease stopped in its tracks. A question that arises, of course, is whether replacing faulty immune cells with healthy microglia through bone marrow transplant would arrest or ameliorate already existing symptoms in humans. We do know of a case in which a girl with Rett Syndrome who was treated for leukemia gained considerable communication skills after a bone marrow transplant, and was able to converse with her mother for the first time in their lives. RSRT is in the process of exploring bone marrow transplant as a treatment modality, with full awareness of the serious nature of such a trial. In research, we are risk-takers. In clinical application, we are conservative and will be examining this carefully as more information emerges." Adds Noël Derecki, "Our encouraging results point to how surprisingly tractable this severe disorder proves to be, at least in the lab. We are currently exploring how bone marrow transplantation might affect Rett symptoms once they have become more advanced, and whether there are other effective ways of modulating immune responses and subsequent effects in the central nervous system."