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Lately, I’ve been obsessed with the A&E tv show Obsessed. It’s about people with obsessive-compulsive disorder, or OCD, who carry out compulsive rituals — such as washing their hands — in order to relieve the anxiety produced by intrusive thoughts. People (myself included) often trivialize OCD in everyday conversation, but the show really illustrates that, at least in severe cases, OCD is debilitating.
No one has pinpointed genes or pathways that cause the condition and, partly because it can be triggered by ordinary stressors, it’s difficult to diagnose. Its biology now becomes even more baffling with the release of two new mouse models of compulsive behaviors, each implicating a different type of brain cell.
Three years ago, Guoping Feng‘s team created mice that compulsively groom themselves by deleting the SAPAP3 gene. SAPAP3 makes a protein expressed exclusively at neuron connections in the striatum, a deep region that’s important for planning movements.
Circuits in the striatum are also highlighted in one of the new studies, which appeared in May in Nature Medicine. By knocking out part of SLITRK5, which encodes a synaptic protein found in the striatum, researchers created mice whose intense self-grooming leads to severe facial lesions.
The second new report looked at mice carrying mutations in the HOXB8 gene. Scientists first noticed in 2002 that these animals feverishly groom themselves and their littermates, but didn’t know why. In the 28 May issue of Cell, they reported that HOXB8 is expressed only in microglia, immune cells that originate in the bone marrow and then migrate to many regions across the brain.
Although the two studies finger very different systems, they might begin to explain how and why OCD overlaps with other psychiatric illnesses, such as autism. For instance, some people with autism have movement problems, or abnormally big striata.
There are also many genetic and neurobiological links between the immune system and autism. Most relevant, a study presented at a meeting last year found that postmortem brain samples from individuals with autism have large numbers of microglia.
How long does a fruit fly sleep? That depends on its genetic make-up, according to research presented this weekend at a meeting of the Genetics Society of America in Boston, Massachusetts.
Researchers identified nearly 1,000 genes in which certain single-letter changes in DNA, called SNPs (for single nucleotide polymorphisms), are associated with the length of sleep.
This preliminary study is the first to come out of the Drosophila Genetic Reference Panel project, a catalogue of variations across the complete genomes of 192 inbred lines of the fruit fly Drosophila melanogaster.
So far, the researchers have deposited raw sequence data from 152 lines in a freely available database, spurring roughly 50 other groups to begin genome-wide association (GWA) studies, which compare the SNPs of flies that show various complex behaviours.
“Once all of the data are out, there will be an army of people who will immediately go after it,” says Charles Langley, a population geneticist at the University of California, Davis, who was not involved in the latest study.
…read the rest of my article at Nature News
The hunt for disease-linked genes gets a lot of attention. What a lot of people don’t realize, though, is that scientists are really looking for ‘functional’ genetic variants — those that do something important. A gene is potentially important if it a) codes for proteins, and/or b) is expressed in a body tissue that makes sense for the disease.
People searching for genes related to brain diseases, for instance, want to know which genes are actually expressed in the human brain. Now, thanks to the Allen Human Brain Atlas, they have a complete reference guide. From ScienceInsider:
The Allen Institute for Brain Science has launched its map of gene expression in the human brain. The institute, started in 2003 with $100 million in seed money from Microsoft co-founder Paul Allen, hopes the atlas will become a valuable resource for scientists studying brain function and disease.
The open access Allen Human Brain Atlas combines four data sets: anatomical images of the human brain obtained by MRI scans (to show gross anatomy), diffusion tensor imaging (which reveals the fiber tracts connecting different brain regions), histology (to show cellular level anatomy), and gene expression data. The result, scientists hope, will provide the most detailed look yet at which genes are active in which parts of the human brain.
The human brain atlas follows the mouse brain atlas released in 2006. A monkey brain atlas is currently in the works.
But the biggest findings in this field may well come from tinier brains.
In a review published 30 March in Molecular Psychiatry, a group of Australian researchersargues thatflies, bees, worms and fish have much to offer psychiatric research.
Even the most primitive nervous systems share some important features with ours. Synapses in the worm Caenorhabditis elegans, for instance, relay chemical messages using the same neurotransmitters we do. The layout of various brain regions in humans and zebrafish is also remarkably similar.
Obviously, these organisms don’t display behavioral hallmarks of psychiatric diseases — imagine measuring the social anxiety of an autistic worm, or hallucinations in a schizophrenic fish. Still, they do show some explicit behaviors that could be informative.
For example, honeybees are dependent on the social structure of their hive; when they are deprived of those interactions, their brain does not wire properly and their memory declines.
These models offer two major advantages over rodents. First, their biology is simpler. C. elegans has just 302 neurons — compared with 4 million in a mouse or 100 billion in a human — and scientists have already worked out the position, shape and connectivity of each one.
Second, they allow for faster, more efficient experimental manipulations. For example, the fruit fly carries roughly 75 percent of all known human disease genes, but because of its 10-day generation time, its genome is infinitely easier to tinker with. Likewise, because zebrafish embryos are transparent, scientists can quickly see structural effects of specific genetic changes.
Some autism researchers have already taken advantage of these model systems. In February, researchers reported that honeybee brains surge with the autism-linked neurexin and neuroligin proteins during learning. Other groups have shown that FMRP, the protein missing in fragile X, controls sleep behaviors in fruit flies.
The reviewers urge scientists to do more “species hopping” — synthesizing findings from many organisms of varying complexity.
Back in March, I wrote about a high-profile criminal case that was the first to use functional magnetic resonance imaging (fMRI). The defendant was a man who raped and murdered several women. His lawyers used the brain scanning technology to argue that their client is a psychopath, and therefore not deserving of the death penalty. It didn’t work.
Now, it looks like another hyped application of fMRI — lie detection — may also have its first day in court, depending on what one judge decides. As ScienceInsider reports:
The defendant in the case is a psychiatrist named Lorne Semrau, who is accused of defrauding Medicare and Medicaid. As reported last week by Wired Science, Semrau claims he had no intention to do so and has retained the services of Cephos, a Massachusetts-based company that sells fMRI-based lie-detection services, to help establish that he is telling the truth. Court documents indicate that Semrau’s lawyer introduced a motion for Cephos CEO Steven Laken to testify as an expert witness on his behalf.
Today [May 13], Judge Tu Pham will hear testimony for and against the inclusion of the fMRI evidence in what’s known as a Daubert hearing, which takes its name from a 1995 Supreme Court case that established guidelines for the admissibility of expert testimony in federal cases. These include factors such as the error rates associated with a given technology, whether it is supported by published research, and whether it is accepted by the scientific community.
No one knows what causes the condition, defined by the inability to recognize and interpret sounds. It appears in an estimated two to five percent of children, and is only beginning to get a bit of public attention.
Last week, speech pathologist Lois Kam Heymann published a book about APD called The Sound of Hope. The book has made a splash thanks to comedian Rosie O’Donnell, who wrote about her 10-year-old son’s struggle with the disorder in the book’s foreword.
APD is often misdiagnosed as autism. Children with either disorder share some overt symptoms — such as a sparse vocabulary, poor grades and trouble paying attention — and both conditions are characterized by difficulties in understanding abstract metaphors. The conversation delays in children with APD can sometimes lead to impaired social interactions and isolation reminiscent of autism.
At the same time, some people with autism report extreme sensitivities to sounds, and a growing number of researchers are taking a close look at auditory processing problems in autism.
For example, using brain imaging, Tim Roberts at Children’s Hospital of Philadelphia has found that the brains of children with autism respond to sounds a split second slower than do those of healthy children. And a few groups have identified distinctive sound patterns in the speech of children with autism.
There are obvious differences between APD and autism. Autism often includes problems in other sensory systems, including vision, touch and smell. Children with autism often have low intelligence quotients or mental retardation, whereas those with APD usually have normal intelligence.
So far, there’s also one promising overlap: children with either condition can be helped by speech therapy and intensive behavioral intervention.
Last summer, I wrote about scientists trying to figure out how to use data gleaned from implanted electrodes in order to predict the onset of epileptic seizures.
Unfortunately, long-term use of those metal electrodes has major drawbacks: irritation, inflammation and scarring. Now comes a new kind of bio-compatible electrode, made of silk! From Technology Review:
This week in the journal Nature Materials, the team reports using a silk electrode device to measure electrical activity from the surface of the brain in cats. Silk is mechanically strong–that means the films can be rolled up and inserted through a small hole in the skull–yet can dissolve into harmless biomolecules over time. When it’s placed on brain tissue and wetted with saline, a silk film will shrink-wrap around the surface of the brain, bringing electrodes with it into the wrinkles of the tissue. Conventional surface electrode arrays can’t reach these crevices, which make up a large amount of the brain’s surface area.
“A device like this would completely open up new avenues in all of neuroscience and clinical applications,” says Gerwin Schalk, a researcher at the Wadsworth Center in Albany, NY, who is not affiliated with the silk electrode group. “What I foresee is placing a silk-based device all around the brain and getting a continuous image of brain function for weeks, months, or years, at high spatial and temporal resolution.”
Imagine, then, the painstaking task of mapping out this complicated wiring diagram. That’s the lofty goal of the Human Connectome Project, a $30 million scheme sponsored by the National Institutes of Health. The agency is reviewing proposals and expects to start funding them by July.
Ever since the famous lesion studies of the 19th century, we’ve learned a lot about the 100 or so distinct regions of the brain, from the spot above the ear that allows us to speak to the area in the back of the head that activates when our eyes see light. But scientists say the real challenge is to understand how these regions connect.
Older connectome projects — such as the one that charted the 302 neurons of the C. elegans worm — relied on making super-thin slices of brain tissue. But this tedious approach just doesn’t cut it for researchers trying to map the brain of a living person in three dimensions.
The Connectome Project aims to study the brain’s major information highways — the large bundles of nerves that link regions — in healthy people. The researchers plan to combine data from several imaging technologies. If two regions light up at the same time during functional magnetic resonance imaging, for instance, that may imply that they are connected. A method that tracks the fiber bundles, called diffusion tensor imaging, could then double-check the links.
If all goes well, the researchers will have the first roadmap of the human brain as early as 2015.
My Nature news feature about using brain scans in court went up yesterday, and the editors are keeping it in front of the pay wall (at least for now). So no reason not to go check it out (plus related podcast)!
The first comment on the piece (pasted below) is a doozy, and I’m curious about what others think about whether psychopathy should be an aggravating or a mitigating factor:
Read the rest of this entry »
Studies in the past two years have found that people carrying specific genetic variants of the hormone’s receptor are at increased risk of developing autistic traits.
Children with autism have low levels of oxytocin in their blood, and a few small clinical trials have shown that getting extra doses of the hormone can improve some characteristic deficits of the disorder, such as body rocking or interpreting emotion from faces and words. Oxytocin is considered a pretty safe drug, because it doesn’t last long in the body and its effects are short-lived.
On 15 February, French researchers showed for the first time that inhaling small doses — three puffs per nostril — of the hormone can also improve social behaviors, the Holy Grail for autism treatments.
In one experiment, a computer ball-tossing game, participants with autism have more interactions with cooperative virtual partners, and report that they trust them more, after inhaling oxytocin. Similarly, when looking at pictures of faces, oxytocin increases the time participants spend looking at the eyes, which they normally avoid.
The results are based on just 13 adults with high-functioning autism or Asperger’s syndrome, though, so it’s not clear whether they would hold in a larger autism population, or in children with the disorder.
Even so, these are arguably the most exciting results of an autism treatment to date, and should encourage companies to place their trust in oxytocin.
