Oxytocin: hope for autism and other social disorders?

The psychiatry I studied twenty years ago is, sadly, almost current today. We haven't really had many substantially new therapies (so much for the speed of medical advancement!). Lately, though, there are signs of a break in the drought. The endocannabinoids may one day provide us new therapies, and more recently oxytocin is looking very interesting:

NIMH: Trust-Building Hormone Short-Circuits Fear In Humans

...Scans of the hormone oxytocin's effect on human brain function reveal that it quells the brain's fear hub, the amygdala, and its brainstem relay stations in response to fearful stimuli....

... "The observed changes in the amygdala are exciting as they suggest that a long-acting analogue of oxytocin could have therapeutic value in disorders characterized by social avoidance," added Insel.

... Having just discovered decreased amygdala activity in response to social stimuli in people with a rare genetic brain disorder that rendered them overly trusting of others, Meyer-Lindenberg hypothesized that oxytocin boosts trust by suppressing the amygdala and its fear-processing networks.

To test this idea, he asked 15 healthy men to sniff oxytocin or a placebo prior to undergoing a functional magnetic resonance imaging (fMRI) scan, which reveals what parts of the brain that are activated by particular activities. While in the scanner, the men performed tasks known to activate the amygdala — matching angry or fearful faces and threatening scenes.

... People with autism characteristically avert their gaze from faces. A fMRI study4 reported earlier this year by NIMH grantee Richard Davidson, Ph.D., University of Wisconsin, and colleagues, found over-activation of the amygdala in people with autism when they were looking at faces. Meyer-Lindenberg said future studies may test oxytocin as a treatment for such social anxiety symptoms in children with autism...

Since Oxytocin is an "old" drug with existing FDA approval, there's a modest chance recent research may produce new treatments within 10 years. This particular result is not surprising given all the recent discoveries about Oxytocin and the amygdala, but it's still interesting and useful. The possibilities for treatment in autism, "attachment disorder" (assuming that's different from autism), and anxiety and paranoid disorders are tantalizing -- all conditions for which we have no effective medications.

I'd guess we have as much as a 20% probability of a new useful therapy -- which is pretty good in this world. Of course the probability of abuse is 100%. Colognes may again become popular among men ...

Autism-class social disorder correlates with blood flow to the inferior frontal gyrus

The researchers studied "high functioning" autistic children, so they were isolating "pure" social disabilities from the cognitive disorders common in many forms of autism. In this group a functional MRI study provided one of the first objective tests for evaluating autism:

Science & Technology at Scientific American.com: Lack of "Mirror Neurons" May Help Explain Autism

... Neuroscientist Mirella Dapretto of the University of California Los Angeles and her colleagues surveyed the brains of 10 autistic children and an equal number of nonautistic children as they watched and imitated 80 different faces displaying either anger, fear, happiness, sadness or no emotion. By measuring the amount of blood flowing to certain regions of the children's brains with a magnetic resonance imaging (MRI) machine, the researchers could determine what parts of the brain were being used as the subjects completed the tasks. The autistic children differed from their peers in only one respect: each showed reduced activity in the pars opercularis of the inferior frontal gyrus--a brain region located near the temple.

This section of the brain has been shown by other studies to be part of the so-called mirror neuron system, which allows humans to understand the intentions of other human beings by observing their actions or imitating their behavior. When damaged, it can interfere with speech.

Although the high-functioning autistic children were able to imitate the facial expressions, they had trouble understanding the corresponding emotional state. The study suggests that the incompletely activated mirror neuron system is to blame. In fact, the less blood that flowed to this region of the brain in each autistic child, the less social ability that child showed--providing more support for the apparent link.

These children could be said to suffer from 'isolated hypofunction of the inferior frontal gyrus' syndrome' (IHIFG Syndrome). If these results hold up we will be able to tease out some of the different conditions subsumed by the generic label of "autism".

Autism, communication disorders and FOXP2 mutations

The FOXP2 gene is currently thought to have been a critical factor in the evolution of human communication. It may be one of the things that allowed the pre-human primate to dominate the world.

Researchers are exploring whether mutations in FOXP2 may be associated with communication disorders, of which autism may be considered one example:

Entrez PubMed - Am J Hum Genet. 2005 Jun;76(6):1074-80. Epub 2005 Apr 22. Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.

FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition...

...Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.

Aging Americans prefer "disciplined" children

I didn't really have the heart to read much beyond the lead of this article: Kids Gone Wild - New York Times. It's perfectly predictable that aging boomers with older children will lose their tolerance for younger children. Predictable, but tedious.

This is a minor matter for most, though the enthusiasm for "discipline" is likely to lead to more use of physical punishment. I expect spanking to become fashionable in a "naughty" sort of way. We will rediscover that it is very hard to hit in a measured manner. Some lessons need to be relearned every twenty years.

It is not a minor matter for autistic, severe ADHD and other special needs children. We can avoid restaurants and public places (though the price may be high for our children), but we do need to take planes, trains and airplanes. The scorn and loathing of the privileged will now be amplified by the righteous indignation of those scorning our lack of "discipline".

It's good training for me to bear such scorn, and perhaps it will chop another thousand years off my stay in purgatory. It will be harsh on our children however. May God spare me the intolerance of the aging when my time comes.

Ironically we do have one "perfect" child, who even at 3 dines with grace, style, and uplifted pinky. It has nothing to do with discipline or training, it is simply her nature. We gracefully accept the associated praise when she alone dines with us, as well as the envious stares of other parents. If only they knew ...

The cruelty of the autism quack

Prometheus debunks the toxic quackery of Dr. Buttar, a cruel parasite upon autistic children and their families. I think I can understand the terrible desperation that drives some parents into the arms of quacks and frauds; but those that prey upon them are the kin of Philip Morris and the corner meth dealer. I'm no libertarian; I think one of the responsibilities of government is to protect these parents and their children -- especially since some of these therapies may be toxic. Even if they are not directly toxic, they suck money and resources that should be used elsewhere.

The old-time Democrats and Republicans were equally guilty of failing to protect vulnerable families from such quackery, but our current regime takes neglect to new levels. The Bushies attacks on logic, rationalism and science only strengthen Dr. Buttar and his peers.

Autism and hypnosis: an interesting research possibility?

I studied hypnosis as a medical student. It was fascinating, but I never did work it into my clinical practice. For one thing, it takes practice to do and time to apply. I'd mostly forgotten about that course, but a New York Times review brought some of it back. The article's research descriptions of hypnotism, belief, perception, and the relationship to hyperconcentration led me to wonder how the studies would work if the subjects were autistic. How would the functional MRIs compare? A google search finds many uninteresting references to hypnotism and autism, but a PubMed search comes up with almost nothing. An interesting research opportunity?

Very annoying: the diagnostic criteria for Asperger's are not all that useful

More confirmation that Asperger's is a very vague clinical concept.

Three diagnostic approaches to Asperger syndrome: implications for research
J Autism Dev Disord. 2005 Apr;35(2):221-34.
Klin A, Pauls D, Schultz R, Volkmar F.
Yale Child Study Center, 230 South Frontage Road, New Haven, CT 06520, USA. ami.klin@Yale.Edu

OBJECTIVE: To examine the implications for research of the use of three alternative definitions for Asperger syndrome (AS). Differences across the three nosologic systems were examined in terms of diagnostic assignment, IQ profiles, comorbid symptoms, and familial aggregation of social and other psychiatric symptoms. METHOD: Standard data on diagnosis, intellectual functioning, comorbidity patterns, and family history were obtained on 65 individuals screened for a very high probability of having autism without mental retardation (or higher functioning autism, HFA) or AS. Diagnoses of AS were established based on three different approaches: DSM-IV, presence/absence of communicative phrase speech by 3 years, and a system designed to highlight prototypical features of AS. RESULTS: Agreement between the three diagnostic systems was poor. AS could be differentiated from HFA (but not from PDD-NOS) on the basis of IQ profiles in two of the three systems. Differences in patterns of comorbid symptomatology were obtained in two of the three systems, although differences were primarily driven by the PDD-NOS category. Only one of the approaches yielded differences relative to aggregation of the "broader phenotype" in family members. CONCLUSIONS: Diagnostic assignments of AS based on three commonly used approaches have low agreement and lead to different results in comparisons of IQ profiles, patterns of comorbidity, and familial aggregation of psychiatric symptoms across the approach-specific resultant groups of HFA, AS, and PDD-NOS.

Researchers need to find more reliable ways to partition their study groups. Asperger's and Autism in general is a "garbage bag" type of diagnosis and is likely to be eventually retired.

Half of Aspergers children have ASD in paternal family history

Half of boys with asperger syndrome have a paternal family history of ASD.

Entrez PubMed J Autism Dev Disord. 2005 Apr;35(2):159-66.
Asperger syndrome: familial and pre- and perinatal factors.
Gillberg C, Cederlund M.
Department of Child and Adolescent Psychiatry, University of Goteborg, Sweden. christopher.gillberg@pediat.gu.se

OBJECTIVE: Study familial and pre- and perinatal factors in Asperger Syndrome (AS). METHODS: One hundred boys with AS had their records reviewed. "Pathogenetic subgroups" were defined according to presence of medical syndromes/chromosomal abnormalities, indices of familiality, and pre- and perinatal risk factors predisposing to brain damage. RESULTS: No major index of pathogenetic factors was found in 13%, a syndrome/chromosomal abnormality in 8%, pre- or perinatal risk 13%, combined pre- or perinatal risk and family history in 11%, and family history only in 55%. COMMENT: About 50% of all boys with AS have a paternal family history of autism spectrum disorder. Pre- and perinatal risks appear to be important in about 25% of cases.

Why paternal only? Might be an artifact of males being more vulnerable to expressing the genetic foundation of the disorder, since the "father" is a large part of paternal history.

Clarifying autism: two types of core behaviors vary independently

More guidance in understanding autism. Core traits, like social impairment and obsesssions, don't necessarily go together.

The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism.

Dev Sci. 2005 Sep;8(5):444-58. Related Articles, Links
Ronald A, Happe F, Plomin R.
Social Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, UK. a.ronald@iop.kcl.ac.uk

Two types of behaviours shown in children - those reflecting social impairment and nonsocial obsessive repetitive behaviours - are central to defining and diagnosing autism spectrum disorders (ASDs). Parent and teacher data on social and nonsocial behaviours were obtained from a community sample of >3000 7-year-old twin pairs. Social and nonsocial behaviours were only modestly correlated, and it was found that some individuals had extreme scores on either social or nonsocial scales but not both. Genetic model-fitting showed that social and nonsocial behaviours are both highly heritable, but their genetic overlap is modest, with most of the genetic influence being specific to either social or nonsocial behaviours. Considering these behaviours separately might help clarify gene-brain-behaviour pathways in future research.

The impliction is these are different genetic syndromes, and clinical autism occurs when an unlucky child gets stuck with either an extreme form of one of them or parts of both. It also relates autism more closely to OCD.

Synthesasia and high IQ autism - case report

[original point via medlogs]

Daniel has fairly severe autism, a high IQ, some extraordinary intellectual abilities, and synesthasia. It's an unusal combination; such case reports define new countries of the mind. Daniel is a generous explorer. One of the most interesting aspects of his story is that he appears to have compensated for some of his core autistic disabilities ...

ABC News: Savant Gives Window to World of Autism

June 11, 2005 — - Daniel Tammet of England can verbally reel off the number pi to 22,500 decimal places in just over five hours -- though he admitted after a recent demostration that it made him "very tired."

Tammet, 26, is a phenomenon. He has done lots of amazing things -- like learning Icelandic, one of the world's most difficult languages, in just seven days.

That's because Tammet is an autistic savant. His extraordinary abilities stem from a combination of autism and a condition known as synesthesia...

... There are perhaps fewer than 50 autistic savants in the world, according to estimates by experts. Those few are people with remarkable, often staggering skills and challenges.

... he doesn't like to come to a beach just a few minutes from his home because it is made up of pebbles — too many even for him to count. That makes him uncomfortable.

Tammet can't drive or do many other things that require basic coordination. Just walking is something he had to do through an effort of will.

"I had to teach myself how to look and how to walk," he said, "how to move myself, how to coordinate myself without falling over, without looking down, without getting absorbed in my own self, my own world."

... After years of effort, Tammet has overcome many of his autistic disabilities. Now living outside of London, not only can he relate to people, he can describe what the experience of autism is like from the inside.

He loves silence, for instance.

"I experience it as like a silvery texture around my head, like condensation running down a window," he said. "If there's a sudden noise, it's like a shattering of that feeling."

... one might say Tammet has come back from the country of autism, which is a very difficult place for researchers and for parents to reach.

"I've come from a place where I felt so lonely, and so unwanted in a way," Tammet said. "And I've come along this road, and I've found this bridge, and I've come across it. And I don't know how, I don't know why, but I'm here and I'm able to talk to you today. And, for me, that's amazing."

There's an emerging meme in autism and brain research that in some people a specialized brain subsystem can compensate for a deficit in a related subsystem. Perhaps the frontal cortex, for example, may compensate for missing capabilities in the prefrontal cortext. If this does occur we may be learn to induce such compensation through training and therapy, even in children and adults who are not gifted.