Starting January 5, 2009, voting for the 2008 Weblog Awards begins—–and this blog, which I’ve been writing since April of 2006, is among the finalists for best Medical/Health Issues Blog. I’m included in some good company, including Respectful Insolence—-The Differetial—-Junk Food Science—-Stirrup Queen.

Thanks to everyone for reading Autism Vox, writing in, sounding off—-it’s been a great year and onward into a new one (very very soon!).

“Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities”—-these are noted in one of the DSM-IV criteria for Autism Spectrum Disorder. A study published in the December 10th Neuron has found that reducing the activity of the gene FKBP12 in the brains of mice affected their synapses, and increased obsessive behavior and “fearful memory.” As noted in today’s Science Daily:

The protein FKBP12 regulates several important cell signaling pathways, and decreasing its activity enhances long-term potentiation in the hippocampus, said Dr. Susan Hamilton, chair of molecular physiology and biophysics at [Baylow College of Medicine] and a senior author of the report. (Long-term potentiation means the enhancement of the synapse or communication between neurons.)

It accomplishes this by fine-tuning a particular pathway called mTOR signaling (mammalian target of rapamycin). The mice in whose brains the activity of the gene was reduced had longer memories and were more likely to exhibit repetitive behaviors than normal mice.

Researchers suggest that their findings might lead to the develop of drugs for autism and also for obsessive compulsive disorders.

Although—-what about the use of such repetitive actions to calm and self-soothe?

Experimental drugs that are said to “correct” symptoms of Fragile X, Rett Syndrome, and tuberous sclerosis complex are now in early-stage human trials, the MIT Technology Review reports. The drugs reduce the activity of a receptor called metabotropic glutamate receptor 5, or mGluR5, and have previously been tested on mice, as reported in the June 25-29 issue of the Proceedings of the National Academy of Science. From the MIT Technology Review:

People with fragile X, the most common form of heritable mental retardation and a leading cause of autism, have a mutation in the FMRP gene, which normally inhibits protein synthesis stimulated by a receptor called metabotropic glutamate receptor 5, or mGluR5.

Last year, [lead researcher and MIT neuroscientist Mark Bear] and Gul Dolen, also at MIT, announced that they could correct abnormal brain development and faulty memory and reduce seizures in affected mice by decreasing mGluR5 activity by 50 percent. “The idea that you could reintroduce function is a sea-change event,” said Emanuel DiCicco-Bloom, a neuroscientist and physician at the University of Medicine and Dentistry of New Jersey, at the neuroscience conference.

Bear has founded a company, Seaside Therapeutics, at which human trials of one of the drugs are now underway. He also says:

“We may have our finger on a biochemical pathway that is applicable more generally in autism.”

More about the STX107, the “lead drug canditate, can be found at the Seaside Therapeutics website.

While studying drug abuse and addiction, researchers at the Ohio State University College of Medicine have found a link between nicotine addiction and autism. Neurexins are proteins that, along with neurologins, are thought to play a key role in the formation and functioning of synapses, of connections between nerve cells. In the new study, a protein made by the neurexin-1 gene was found to have a very particular role, as noted in today’s Science Daily:

The discovery identified a defining role for a protein made by the neurexin-1 gene, which is located in brain cells and assists in connecting neurons as part of the brain’s chemical communication system. The neurexin-1 beta protein’s job is to lure another protein, a specific type of nicotinic acetylcholine receptor, to the synapses, where the receptor then has a role in helping neurons communicate signals among themselves and to the rest of the body.

This function is important in autism because previous research has shown that people with autism have a shortage of these nicotinic receptors in their brains. Meanwhile, scientists also know that people who are addicted to nicotine have too many of these receptors in their brains.

“If we were to use drugs that mimic the actions of nicotine at an early time in human brain development, would we begin to help those and other circuits develop properly and thus significantly mitigate the deficits in autism? This is a novel way of thinking about how we might be able to use drugs to approach autism treatment,” said Rene Anand, associate professor of pharmacology in Ohio State University’s College of Medicine and principal investigator of the research.

“It would not be a complete cure, but right now we know very little and have no drugs that tackle the primary causes of autism.”

Cholinergic agents are drugs which play a role in countering nicotine addiction in the brain. It’s speculated that these medications, after “retailor[ing],” might help autistic individuals by increasing the level of neurexin-1 beta protein in their brains. How this might specifically help autistic individuals is only alluded to—-perhaps it might be more helpful to think about how medications can, in some cases and in discrete ways, help some autistic individuals, over and above focusing on the notion of a drug that would “cure autism“?

The research was presented today at the Society for Neuroscience meeting in Washington, D.C.

This summer has seen its share of discussion of the challenges of traveling with special needs children (on airplanes, in particular); more recently, there’s been discussion of traveling with autism assistance dogs, too. The August 12th International Herald Tribune describes the difficulties of caring for a special needs child when you, the parent, have to travel for work.

Some special needs children cannot understand that a parent is away. “When you have a child who doesn’t speak, I can’t explain anything,” said Candi Nichols Carter, a television producer in Chicago, and the creator of the children’s entertainment company It’s Hip Hop, Baby! “I had to go to Vegas for four days to work on a show,” she said. “I can’t explain that to him, that ‘Mommy’s going to be gone for four days.’ The next day, he wakes up and his mother is just gone. It’s got to be traumatizing.”

Nichols Carter’s 5-year-old child, Emerson, presents a multitude of challenges. In an e-mail message, Nichols Carter wrote: “Emerson is a child with a mental disability. We found out a year and a half into his life that he was born with a chromosome abnormality. As a result he had many physical problems early on and currently struggles with a severe speech delay.”

Jim or I traveling for work occurs pretty infrequently. We try to only go to conferences that are close enough to travel to and return from within one day. I make visual and picture schedules for Charlie, talk succinctly and straightforwardly about us leaving and returning, and make sure there are lots of activities to keep Charlie occupied. I also try (if we’re gone for a longer period of time, which is a very rare occurrence, as in it hasn’t happened for quite awhile) to have my parents come out from California. Charlie’s medical needs are nothing too unusual—he needs to take his medications at certain times and it’s essential that whoever is taking care of him know how to help him stay calm and allay his anxiety.

Fortunately both of us don’t have to travel much for work, just the regular rigors of the daily car-and-train-and-subway commute.

A letter abstract in the June 22nd Nature Medicine is entitled Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Tuberous sclerosis is a rare genetic disease that affects the central nervous system and causes benign tumors to grow on the brain, kidneys, heart, eyes, lungs, and skin. Those with TSC can also have seizures, mental retardation, behavior problems, and skin abnormalities as well as developmental delays and autism: In fact, half of those with TSC have autism and epilepsy. Mutations in one of two genes, TSC1 and TSC2, been have identified as causes of TSC. The Nature Medicine abstract also notes that “even individuals with tuberous sclerosis and a normal intelligence quotient (approximately 50%) are commonly affected with specific neuropsychological problems, including long-term and working memory deficits.”

In the study, which was carried out by researchers from UCLA, mice were bred to have TSC; they specifically had deficits in learning and memory. By giving the mice rapamycin, a drug that has been approved by the FDA to fight tissue rejection following organ transplants, their learning and memory deficits were reversed. From a press release containing interviews with the study’s researchers:

Rapamycin is well-known for targeting an enzyme involved in making proteins needed for memory. The UCLA team chose it because the same enzyme is also regulated by TSC proteins.

“This is the first study to demonstrate that the drug rapamycin can repair learning deficits related to a genetic mutation that causes autism in humans. The same mutation in animals produces learning disorders, which we were able to eliminate in adult mice,” explained principal investigator Dr. Alcino Silva, professor of neurobiology and psychiatry at the David Geffen School of Medicine at UCLA. “Our work and other recent studies suggest that some forms of mental retardation can be reversed, even in the adult brain.”

“These findings challenge the theory that abnormal brain development is to blame for mental impairment in tuberous sclerosis,” added first author Dan Ehninger, postgraduate researcher in neurobiology. “Our research shows that the disease’s learning problems are caused by reversible changes in brain function — not by permanent damage to the developing brain.”

………

“Memory is as much about discarding trivial details as it is about storing useful information,” said Silva, a member of the UCLA Department of Psychology and UCLA Brain Research Institute. “Our findings suggest that mice with the mutation cannot distinguish between important and unimportant data. We suspect that their brains are filled with meaningless noise that interferes with learning.”

“After only three days of treatment, the TSC mice learned as quickly as the healthy mice,” said Ehninger. “The rapamycin corrected the biochemistry, reversed the learning deficits and restored normal hippocampal function, allowing the mice’s brains to store memories properly.”

Regan commented about the study on an earlier post; the researchers’ association of intelligence with learning and memory is particularly interesting to me, and also Dr. Silva’s definition of memory as being “‘as much about discarding trivial details as it is about storing useful information.’” My son Charlie has a great and powerful memory: He never seems to forget a therapist or teacher, a place we’ve been and the route to it, a toy or food or activity that he’s liked a lot. He tends to get stuck—fixate—on those first, earlier things he’s learned and to have trouble learning new things (getting used to new teachers and therapists, going to new places along new routes, playing with new toys and trying new foods and activities). Often it seems that the first of many things is what “something is” for Charlie and teaching him otherwise evokes cognitive dissonance,” as if he’s pushing against something in his brain to accommodate for something new.

I’ve noted Charlie’s longstanding struggles to learn the alphabet and language (both understanding and speaking it). Regarding the alphabet: We started to teach it to him when he was about 3 1/2; he’d had no trouble learning numbers. It has taken years for Charlie to recognize the letters and sometimes he seems to be focusing on certain details of the letters—certain shapes and the fact that to many letters rhyme with “ee”—and not to know what aspects he should focus on.

The further results of this study will be of interest to us.  But if there were a medicine to help “reverse” memory and learning deficits, I think that Charlie’s thinking and being would be in many ways the same. He takes in so much of the world around him and I truly think his emotional intelligence is the same as other children his age: As I wrote, my husband Jim has injured his back very seriously and, consequently, has not be able to be at all as active as he is used to and as he loves to be. Jim can barely walk right now (this is my husband who easily runs a mile and a half to train station and through Manhattan streets instead of taking the subway, with a bag stuffed with books and papers). I’ve been explaining to Charlie that his dad injured his back and that Charlie has to do more for himself—-and Charlie has been getting out of bed on his own when I ask (instead of getting tugged and semi-carried; he’s always had trouble getting up in the mornings); he’s pulled on his clothes and grabbed his backpack and run down the stairs for the bus with minimal asking. What is this thing called intelligence, I sometimes wonder?

Jennifer Buettner, who has three young children, has created a new company called Efficacy Brands which makes placebos for children. The company will see cherry-flavored dextrose tablets (”Obecalp”—-guess what word that is, spelled backwards?); $5.95 for a bottle of 50. Buettner came up with the idea while taking care of a niece with a “raging case of hypochondria,” the May 27th New York Times notes:

“This is designed to have the texture and taste of actual medicine so it will trick kids into thinking that they’re taking something,” Ms. Buettner said. “Then their brain takes over, and they say, ‘Oh, I feel better.’ ”

The NY Times quotes a number of doctors who note that the placebo effect can be “‘unpredictable’” and who wonder if “giving children ‘medicine for every ache and pain teaches that every ailment has a cure in a bottle.” Buettner notes that she is prepared for controversy. The overprescription of antibiotics (in some cases, to parents who just want to give their child “something”) is cited; Buettner call this “‘a serious problem” and thinks that “‘there needs to be an alternative.’”

The premise behind “Obecalp” has got me reflecting about the various supplements and medications we’ve given Charlie. When he was younger, we tried SuperNuthera, DMG, TMG, Culturelle, cod liver oil, magnesium, vitamin E, BrainChild vitamins, and probably some others and I know that I looked for results and I liked to think I saw them. With something like DMG, the effect of “more attention” or “clearer speech” often seemed immediate, and soon faded. Charlie doesn’t take any supplements (aside from regular vitamins and calcium) any more; he does take medications and attempts to have him not take these have had immediate (and not desired) results.

I’m reminded again of how parents yearn so totally to help their child. I used to worry about what if Charlie never talks and anything that said “helps with language” or “enhances communication” got several looks from me. But I know that it’s been years of teaching, speech therapy, physical exercise, and just plain old growing up that have helped Charlie learn to talk: When he’s frowning as he tries to imitate how we hold our mouths to say words, I can see how he’s working at getting his mind and muscles to coordinate and produce—language.

And then there’s no guessing, if it was the pill—the placebo—or not.

Over at Help My Hurt, Marijke Durning has a poll up about what you think about giving a child a placebo.

The highpoint of the week for us was Thursday night’s reading in conjunction with the Artistic Spectrum exhibit—–and Charlie also had a lot of things to say himself.

• Did Your Child Reach Her or His Gross Motor Milestones?
  Some parents note that their children had gross motor delays (Charlie did), while others said their child did not. Indeed, some parents whose children met all their gross and fine motor milestones then had other delays in social and communicative skills.
• About This “Autism Dilemma”
  According to health journalist Alison Rose Levy, there is an “autism dilemma” afoot, in which parents of autistic children speak emotionally and from the heart about what they think (a vaccine, for instance) “caused” their child to become autistic, while “aloof doctors” listen and respond with well-reasoned appeals to the evidence of science.
• 2 Hypotheses: Autism Epidemic and Diagnostic Substitution
  Is the increase in the number of autism diagnoses (especially in children) due to some external factor or agent; to, for instance, something in the environment—-in the physical world—that has changed? Or, is the increase due to a kind of internal change in us, in how we think about and understand and perceive the world?
• Physicians, Vaccines, and Autism
  Physicians, that is, were aware of claims about a vaccine-autism link when such first came out in 1998; there was indeed a “noticeable drop in reported use of the vaccine in 2000.” Afterwards, once reports of a claim were refuted (by a report from the Institute of Medicine, among others), doctors again defended the value of immunizations.
• Dyslexia is Different in Chinese and in English speakers
  Scientists at the University of Hong Kong have found that the cause of a child’s dyslexia depends on what language they are trying to learn.
• Excluded
  Parents of eight autistic children in Lakewood, Colorado, are objecting to where a classroom for children has been located—in a portable classroom outside the main school, a story in the April 9th 9news reports.
• Share and Share Alike
  Charlie offers me a California roll.
• The Cause of It All
  Because of Charlie, I find myself reading at the JCC’s “Artistic Spectrum Lif Café”; meeting many new faces; and riding the subway with Cliff Schumacher. Great times!
• The “Subpopulation” of Mitochondrial Autism
  How prevalent are mitochondrial conditions among autistic children?
• A Conversation
  Charlie tells me where he wants to go, and why.

A study in the March 2008 volume of Pediatrics on psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders noted that there is “ongoing debate” about the uses of psychotropic medications. Only Risperidone, an atypical neuroleptic, has received FDA approval to treat autistic children for aggression and irritability. The AAP study also noted that “medication use is common among children with ASDs and seems to be increasing.” The study sample included 60,641 children under the age of 21 with an autism spectrum disorder diagnosis or an Asperger syndrome diagnosis.

Most of the children in the study were 6-11 years old (45%); most were male (78%) and white (50%); and most were eligible for Medicaid because of disability (71%).

Of these children, 56% used at least 1 medication during 2001; among those who received any medication, 20% used 3 concurrently. The most commonly used medications were neuroleptic drugs (31%), then antidepressants (25%), stimulants (22%), mood stabilizers (21%), anxiolytic drugs (12%), and sedatives (3%).

While older children were more likely to take medications than younger children, it was noted that “use was quite common” in children aged 0 to 2 years (18%) and 3 to 5 years (32%). And,

Among 0- to 2-year-olds, sedatives were most common; among 3- to 5- and 6- to 11-year-olds, both neuroleptic drugs and stimulants were most common; and in the oldest 2 age groups, neuroleptic drugs were most common.

The researchers acknowledge certain limitations to their finds, due to the children all being enrolled in Medicaid:

Use among the Medicaid population may be higher than in the general ASD population because Medicaid typically has less restrictive formulary and copayments than private insurance. Also, Medicaid-eligible children may be more severely affected than the general population of children with ASDs; that 70% of children in this study qualified for Medicaid because of their disability provides some evidence of this.

As I have noted before, my son has been taking both Risperdal (Risperidone> and Zoloft (Sertraline) for a few years, to help him with aggressive and self-injurious behavior and anxiety. We tried Ritalin for a very few days; it did increase Charlie’s ability to focus, but it also made him haunted and nervous and completely suppressed his appetite. We have tried very hard to keep the dosages as low as possible and have only used these medications in combination with educational therapies. Prior to Charlie taking Risperdal and Zoloft, we tried giving him various nutritional supplements, whose effects were temporary at best in helping him with his most difficult behaviors. I consider the medications another tool to help Charlie, and one that we have to monitor very carefully, due to Charlie’s limited language and speech.

More than a few people have raised questions about the long-term effects of these medications on children and on giving a child more than one medication. I was surprised to see how many young children—-aged 0-2—are given some type of psychotropic medication. The researchers single out the “high levels of use of many different psychotropic agents, often in combination” as a concern, especially in these being given to young children “in whom the effects of these medications on development have not been well studied.” They also note a need for more studies in the use of sedatives for young children, and about the use of psychotropic medications in combination for children with autism. I would also appreciate studies about the long-term use of these medications in children—debate on this issue will indeed be going on for more than a little while.