Category: Autistic Spectrum Disorders

Probably there are multiple genes and multiple avenues for the development of autistic traits in children. There is recent news that one particular gene — the shank3 gene — may be responsible.

Some children strongly avoid social interactions (they arch their back & look away) as infants. Other children develop normally only to suddenly lose all language and social interests typically around the age of 18-24 months. Fascinating, about one quarter of U.S. children who meet criteria for a diagnosis of autism at age 3 will “shed” that diagnosis before they reach adulthood.

So, one wonders whether a single gene is responsible for such wide variations in how autistic behaviors are expressed during a child’s development. See below what scientists say about the shank3 gene.

MONDAY, March 21 (HealthDay News) — Scientists report that mutating a single gene produced mice with two of the most common autism traits, a finding they say could one day lead to the development of drugs to treat autism.

Currently, there are no effective drugs to treat the disorder.

Mutating the shank3 gene led to compulsive repetitive behavior and avoidance of social interaction in the mice, apparently caused by impaired communication between brain cells, said the researchers at Duke University and the McGovern Institute for Brain Research at the Massachusetts Institute of Technology.

The shank3 gene has been implicated in human autism.
The study was published online March 20 in Nature.

“We now have a very robust model with a known cause for autistic-like behaviors,” senior author Guoping Feng, a professor of brain and cognitive sciences at MIT, said in a McGovern Institute news release. “We can figure out the neural circuits responsible for these behaviors, which could lead to novel targets for treatment.”The genetically altered mice also provide a way to assess experimental autism drugs before they’re tested in humans.

Scientists acknowledge that research involving animals often fails to result in beneficial treatments for humans.

The U.S. National Institute of Neurological Disorders and Stroke has more about autism

DrCameronJackson@gmail.com

The Friends Program, located in Palo Alto, California, is a therapeutic group designed to address the developing needs of young children with Asperger’s Syndrome and their families.

Laurie Levanthal-Belfer, Ph.D. is the Director of The Friends Program and can be reached at Dr.LaurieLB@gmail.com and on the web at www.thefriendsprogram.com

Dr. Levanthal -Belfer was the speaker for Asperger’s Disorder: A Developmental Approach to Understanding Asperger’s Disorder, Assessment and Intervention held in Aptos, CA on 2-26-2011. This was a conference attended by psychologists, nurses, marriage and family counselors and interested public.

What did attendees learn? Some notes:

Asperger’s Disorder became diagnosis in 1994 and will not be a separate diagnosis in the next DSM-V expected out in a year or so. Asperger’s Disorder will be eliminated. Instead there will be Autistic Spectrum Disorder.

What I learned looking at my notes: Asperger’s Disorder children at age 4 or 5 play more like a child of 2 or 3. They have intense interests which may change but the intensity of the interest is notable. Transitions are difficult for them. They have one way to go to school and if a parent or other person deviates that will spark a melt down. They cannot take the perspective of the other. The therapy groups work a lot on white lies and how to tell them. Children with Asperger’s Disorder are “black-white” children that think there is only one way to do things.

Parents cannot ask children with Asperger’s Disorder, “What did you do today?” Think of Asperger’s Disorder children like a computer with files. You have to find the right file and open it. Likewise, a parent has to inquire, when you were on the playground during recess what game did you play? That kind of specific questioning — akin to opening a specific file — helps a child to know how to answer a question.

It’s important that parents “cut the white space” — the unstructured time. When children with Asperger’s Disorder know exactly what to do they talk less about their current intense interest. Many children with Asperger’s Disorder have sensory regulatory issues which Dr. Leventhal-Belfer thinks are related to anxiety. Asperger children can be so loud themselves and yet over sensitive to noise. Usually when doing an intake some family members are identified as having Asperger symptoms.

Dr. Laurie Levanthal-Belfer likes the Robert’s test for assessment. The Robert’s test is a projective test that shows social situations. She uses kinetic family drawings to see how family members relate to each other. Often one parent has traits highly similar to the child with Asperger’s Disorder. Dr. Levanthal-Belfer has found that the same strategies that work with children also work with the spouses that have Asperger’s Disorder traits.

Concerning assessment: Dr. Levanthal-Belfer asks for home videos, does school observations, takes a developmental history and does a parent interview. She will use the Wechsler IQ tests for assessing cognitive abilities. She assesses how the parent and child interact by having them build a house out of blocks, do clean up, do a learning task (puzzle, read a book, teach the child how to be President). She wants to see how the parent leads the child and vice versa.

Of note for therapists: Dr. Levanthal-Belfer said that insurance pays for treatment but not for diagnosis. She asks, but how do you do appropriate treatment without accurate diagnosis? Linda Lotspeich, M.D. suggests that therapists give 3 different diagnosis depending on the audience.

She tells graduate students to first rule out Autism before considering Asperger’s Disorder.

California schools take the position that if the child can do age appropriate work then they will not offer an IEP.

The key part to The Friends Program is the parent component. And generalization is key. written by Cameron S. Jackson DrCameronJackson@gmail.com

Ritalin helps about 70-80% of children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) with a 1 1/2 percent who discontinue due to side effects. Now research shows that Ritalin helps children with Autistic Spectrum Disorders — not to the same extent and with more side effects. A 2005 study shows that Ritalin helps 50% of children on the spectrum with a an 18% discontinue rate due to side effects.

My question: What is helped the most? Executive functioning abilities (attention, planning, sequencing) or impulsively or what?

See the following research article:

“Hyperactivity, distractibility, and impulsivity are common symptoms in children with autism and other pervasive developmental disorders (PDD). Children with PDD who experience these symptoms are not considered to also have Attention Deficit Hyperactivity Disorder (ADHD). This is because their symptoms of hyperactivity and inattention are thought to be secondary to the autistic symptoms and/or intellectual disability, and also the response to treatment may be different. A number of studies have explored the use of stimulants such as methylphenidate in typically developing children with ADHD, but few have examined the use of methylphenidate in children with PDD. This study sought to determine the efficacy and safety of methylphenidate in children with PDD and hyperactivity.

Seventy-two children with PDD and moderate to severe hyperactivity participated in a 1 week test-dose phase to see how well they tolerated methylphenidate. Each child received placebo for 1 day, then increasing doses of methylphenidate (low, medium, high) for 2 days each. The 66 children who tolerated the test-dose were then randomly assigned to the next 4 week phase. The trial was double-blind, meaning that neither child, parent, nor doctor knew whether the children were receiving active drug or placebo. It was also a crossover trial. In a crossover trial subjects are randomly allocated to one of two groups. Subjectsallocated to the methylphenidate group receive methylphenidate first, followedby placebo. Vice versa subjects in the placebo group receive placebo first, followed by methylphenidate treatment. This designallows contrasting the response of a subject to placebowith the same subject’s response to methylphenidate. Each child therefore received placebo and the 3 different dosage levels (provided they were able to tolerate the dosages during this longer phase). Children who responded positively during the crossover phase were then entered into an 8 week open label (i.e. no longer blinded) continuation phase at their best dosage. The primary outcome measure of the study was the hyperactivity scale of the Aberrant Behavior Checklist (ABC).

The investigators found that methylphenidate was more effective in improving symptoms of hyperactivity and inattention than placebo in children with PDD (49% response rate). Adverse effects were more frequent with methylphenidate than placebo and included irritability, decreased appetite, difficulty falling asleep and emotional outbursts. There was an 18% discontinuation rate due to adverse effects. The 49% response rate is less than the 70% – 80% response previously reported in a large study of children with ADHD; the 18% adverse event rate for children with PDD was higher than the 1.4% rate reported in the aforementioned study of children with ADHD.

Conclusions

The investigators conclude that methylphenidate is a reasonable choice for treating hyperactivity in the context of PDD given the response rate of 49%, with the caution that there is a strong possibility of adverse effects.

Is it time to view autism as a psychological trait similar to intelligence? Some researchers say yes.

If true, that most Americans have some “autistic traits” and a few of us are very low or very high in “autistic traits”. If autism is normally distributed — in the shape of a bell curve — then it’s time that standardized tests for measuring autism are developed similar to how intelligence is measured.

If true, then the supposed “gold standard” for assessment of autism in toddlers may not be so golden after all. Why?

The ADOS developed by Lord et al measures autistic spectrum traits the way a thermometer or a ruler does. The difference between 2 and 3 is the same as between 12 and 13. But if autism is normally distributed then different measures — with a different kind of “ruler” need to be used.

Background to how intelligence (I.Q.) is measured:

The intelligence of 2 out of 3 persons in the U.S.lies between 85 and 115. Only 2 or so persons have an I.Q. of 70 or lower. Likewise, only 2 or so have an I.Q. of 130 or higher.

In Feb., 2008, Carrie Allison et al published a paper: The Q-Chat: Quantitative Checklist for Autism in Toddlers. A normally distributed measure of autistic traits.

There is an old adage: an hour before 12 is worth two afterwards. Any truth to that? The Chinese royal families thought the best time to sleep was between the hours of 11 pm and 2 am. For sure many people report that going to bed much later than normal and sleeping 7-8 hours does not result in feeling refreshed.

So for people with Autistic Spectrum Disorders and compromised executive functioning abilities — what to do?

Routine and patterns creating ingrained habits may assist. So first, figure out how to get to sleep at a set time. Then start moving that time back so you can sleep when it is dark and get up when it is light – or as close that as possible. In the evening stop both mental and physical exertion a couple hours before going to bed and plan to be in bed by around 10 pm. Do boring if need by, relaxing tasks the couple hours before bed. Using either a prescription or other means plan to go to sleep around 11 and up by 8 or so.

By Martin W. Schwartz
The best time to sleep varies from person to person, but as a general rule the internal human clock (Circadian Clock) gears people to sleep when it is dark outside and remain awake during hours of light.

Some people, like this writer, are “night owls” meaning that their Circadian rhythms are such that becoming tired does not set in until the “wee” hours of the morning (between 2 AM and 5 AM). For us, going to sleep early is a chore, often requiring the use of prescription (Ambien, Sonata, Lunesta) or non prescription (.3 mg of Melatonin) sleep aids.

Although the Circadian clock can be “reset” in a sleep laboratory or by a routine that gradually has the person going to sleep 10 minutes earlier each night, for “night owls” it is very easy to slip back into the old routine simply by sleeping late on a single day.

For people with no disturbances in their Circadian rhythms, the best time to sleep is about 5-6 hours after eating their dinner, which works out to sometime between 11PM and Midnight. Going to sleep the same time every night, seven days a week, avoiding late evening snacks with caffeine, theobromine (chocolate) or salt, will help to prevent insomnia by keeping the Circadian clock in synch with the actual time of day/night. And AVOID NAPS during the day. If you must take one it should be no lnger than 45 minutes.

Sleep deprivation is a huge problem in industrialized nations and other than spending time in a sleep laboratory, medical science has come up with very little to treat chronic or intermittent insomnia.

New way of doing Cognitive Behavioral Therapy (CBT) is to take a medication just before CBT that enhances learning and reduces fear and combine it with exposure therapy to address the fear. See below:

” The new data provide more evidence that D-cycloserine enhances the efficacy of exposure therapy in people with phobias. An earlier study conducted at Emory University demonstrated similar results in individuals with acrophobia, the fear of heights. According to Stefan Hofmann, associate professor of clinical psychology and lead investigator of the BU study, his team’s research offers a number of complementary features: it represents the use of DCS in a common anxiety disorder known for its marked distress and disabling effects; it examines treatment outcomes for a condition that has been the target of large-scale combination treatment trials, with little advantage shown for the addition of drugs over behavior therapy alone; it utilizes a longer course of therapy; and, it utilizes clinicians from several sites and both individual- and group-treatment formats that are consistent with the ways in which behavior therapy is provided in clinical settings.

“Studies like this may usher in a new strategy for combining medications and cognitive-behavior therapy,” suggests Dr. Otto. “Instead of simply combining medications and therapy that are each designed to reduce anxiety and avoidance, the use of DCS is directed toward making the therapeutic learning in cognitive-behavior therapy stronger. Medication use is limited to only a few doses, taken before therapy sessions.”

Researchers from the anxiety clinics at Massachusetts General Hospital and Southern Methodist University also participated in the study.

Clinical trials to start using D-Cyclosrine to treat socialibility dificulties.

NORFOLK, Va., Dec. 11 (UPI) — A U.S. researcher says a possible drug to treat impaired sociability in those with autism may be a breakthrough.

Dr. Stephen Deutsch of Eastern Virginia Medical School in Norfolk says the novel treatment strategy will soon be entering the clinical trial phase.

“Persons with autism spectrum disorders are either disinterested in social interactions or find them unpleasant. They often don’t understand what other people are thinking or feeling and misinterpret social cues,” Deutsch says in a statement. “Sadly, persons with autism spectrum disorders are often painfully aware of their limited sociability, which can lead to profound feelings of sadness and frustration.”

Deutsch and colleagues have used mouse studies — in particular a strain of mouse with limited sociability who — unlike normal mice — create distance with other mice to avoid social contact to test the drug.

The medication originally developed to treat tuberculosis but known to affect social behavior — called D-Cycloserine seems to address deficits of sociability in the socially deficient mice — the mice behave as a normal mice would when placed near another mouse.

Deutsch is scheduled to present the findings at Eastern Virginia Medical School’s Quarterly Autism Education Series.

An analogue of the amino acid D-alanine with broad-spectrum antibiotic and glycinergic activities. D-cycloserine interferes with bacterial cell wall synthesis by competitively inhibiting two enzymes, L-alanine racemase and D-alanine:D-alanine ligase, thereby impairing peptidoglycan formation necessary for bacterial cell wall synthesis. This agent may be bactericidal or bacteriostatic, depending on its concentration at the infection site and the susceptibility of the organism. In addition, D-cycloserine is an excitatory amino acid and partial agonist at the glycine binding site of the NMDA receptor in the central nervous system (CNS); binding to the central NMDA receptor may result in amelioration of neuropathic pain.

by Cameron Jackson DrCameronJackson@gmail.com

MRI’s soon may be able to objectively and quickly identify children at risk of autistic spectrum disorders. And, further identify the sub-types or different expressions which can lead to more individualized treatment.

We know that cognitive behavioral therapy for depression can result over time in substantial changes in how the brain functions. So, likewise some day using MRI’s to measure change it should be possible to re-train the two hemispheres of brains to better communicate. And thereby reduce the symptoms of autistic spectrum difficulties.

Thus, instead of looking at autism as a lifelong developmental disorder we may view autism as a developmental delay which can be substantially improved.

Diffusion tensor MRI may yield autism diagnosis
By University of Utah Health Services | October 15, 2010

“University of Utah medical researchers made an important step in diagnosing autism through diffusion tensor imaging, an MR technique that could help healthcare providers identify the problem much earlier in children and lead to improved treatment and outcomes for those with the disorder.

In a study published in Cerebral Cortex online, researchers led by neuroradiologist Dr. Jeffery Anderson a University of Utah assistant professor of radiology, used MRI to identify areas where the left and right hemispheres of the brains of autism patients do not properly communicate with one another.

Those areas are in “hot spots” associated with functions such as motor skills, attention, facial recognition, and social functioning–behaviors that are abnormal in autism. Scans of people without the disorder did not show the same deficits.

“We know the two hemispheres must work together for many brain functions,” Anderson said. “We used MRI to look at the strength of these connections from one side to the other in autism patients.”

Other than increased brain size in young children with autism, there are no major structural differences between the brains of people with autism and those who do not have the disorder. It has been long believed more profound differences could be discovered by studying how regions in the brain communicate with each other.
The study, and other work University of Utah researchers are doing, using diffusion tensor imaging reveals important information about autism. The advances highlight this strategy as a potential diagnostic tool, so patients could be screened objectively, quickly, and early on when interventions are most successful. The advances also show the power of MRI to help scientists better understand and potentially better treat autism at all ages.

“We still don’t know precisely what’s going on in the brain in autism,” said Dr. Janet Lainhart, an associate professor of psychiatry and pediatrics at the University of Utah, and the study’s principal investigator. “This work adds an important piece of information to the autism puzzle. It adds evidence of functional impairment in brain connectivity in autism and brings us a step closer to a better understanding of this disorder. When you understand it at a biological level, you can envision how the disorder develops, what are the factors that cause it, and how can we change it. ” An increasing number of studies have shown abnormalities in connectivity in autism, but this study is one of the first of its kind to characterize functional connectivity abnormalities in the entire brain using MRI rather than in a few specific pathways. The research involved about 80 autism patients between the ages of 10-35 and took about a year and a half to complete. The results will be added to an existing autism study following 100 patients over time.

“The longitudinal imaging data and associated knowledge gathered forms a unique resource that doesn’t exist anywhere else in the world,” said Lainhart.

In addition to someday using MRI as a diagnostic tool for autism, researchers also hope to use the data to biologically describe different subtypes of autism.

“This is a complex disorder that doesn’t just fall into one category,” Lainhart said. “We hope the information can lead us to characterizing different types of autism that may have different symptoms or prognoses that will allow us to identify the best treatment for each affected individual.”
The collaborative autism imaging research group led by Lainhart is working together to develop methods to use brain imaging to better understand autism and improve the lives of affected individuals. It includes researchers in the departments of psychiatry, radiology, and pediatrics, the Neurosciences Program, the Scientific Computing and Imaging Institute, and The Brain Institute at the University of Utah, as well as collaborators at Brigham Young University, the University of Wisconsin, and Harvard University.