Friday, December 09, 2005

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 ...

Monday, December 05, 2005

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 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".

Thursday, December 01, 2005

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.