What is clear from this recent paper (Neal et.al. Patterns and rates of exonic de novo mutations in autism spectrum disorders, Nature, advance online publication, http://dx.doi.org/10.1038/nature11011) is that ASD is highly polygenic in origin, i.e. hundreds of genes influence autism risk. Getting to this answer, including two genes in particular that were determined to be very strongly linked with autism (CHD8 and KATNAL2), was a real technical achievement in that in involved analyzing the genomes of 175 trios (mother, father, autistic child). Sequencing 525 human genomes is something that would have been unimaginable just a few years ago. While it is clear that we still have much to understand about this complicated disease, the technological limitations that previously limited progress are beginning to fall away. Hopefully many more important clues are just around the corner.

Recently, a group from Naples reports that D-Aspartic acid functions as a neurotransmitter in both a mammal the rats (Rattus norvegicus), and a mollusk (Loligo vulgaris). D-Aspartic acid (D-Asp) has been known to scientists for well over a century. However, its role as a neurotransmitter was only now confirmed by the work presented by D’Aniello et.al.

The brain is usually thought of in its own category when considering our organs; deservedly so, since it seems to be the seat of our personal identity, our selves.  Still, the molecules we think of as neurotransmitters (GABA, glutamate, serotonin, etc.) we most often isolated from other parts of the body, and have roles in biology unconnected with neurotransmission.

Presence in the brain is of course not the qualifying factor for describing any particular molecule as a neurotransmitter. The D’Abuello et.al demonstrate not only the presence of D-Asp acid in high concentrations in synaptic vesicles, but also show that there are specific post-synaptic receptors for D-Asp which trigger signal-transduction of cAMP upon binding of the D-Asp ligand.

While this is a very focused study, it is clear from a variety of scientific findings that music education is an essential and indispensible component of childhood education in general. Findings from Dr. Kraus’ lab have also indicated that the areas of the brain that are enhanced by musical training are the same areas found deficient in cases of dyslexia.

How many students with possible attention deficits, dyslexia, or other developmental difficulties could be helped by music education? Yet these programs are often the first to be cut when school budgets are tightened.

I’ve often wondered how professional musicians are so wonderfully educated, given the enormous amount of time they have to dedicate to their craft. But when you think about how music could help students better hear and comprehend sounds even in a complex aural environment (e.g. a classroom), it is not surprising given that in music, you are in a real sense listening to perhaps a half a dozen or more conversations or more. In an orchestra, you have to listen to yourself, your section, and all the other instruments in order to play correctly. As a skilled listener, every note is an important component of the piece, and you are easily disturbed (and perhaps later delighted) when you first listen to another recording of your favorite work to find some notes emphasized, diminished, or seemingly eliminated.

The Mozart effect (or at least the over-hyped media and commercialization of it) notwithstanding, music is more than entertaining, it can be educational.

Check out this youtube video (http://www.youtube.com/watch?v=PmWRttCo7lo ) of one of my favorite (educated) musicians, Mistko Uchida, as she explains the Schoenberg Piano Concerto (a personal favorite). I love her explanations of what you are hearing, especially at around 5:20 in this particular clip. To the uninitiated some “classical” music sounds like a jumble, but there is really so much beneath the surface. Look and listen to her play in this clip (http://www.youtube.com/watch?v=ct47T9_liOU) for a good brain workout.

What are CNVs?

Copy number variations are spontaneous mutations in the genome that result in duplications or deletions of the genomic sequence. Duplications can produce extra copies of a gene, deletions can remove it altogether. CNVs are an interesting biological phenomenon because they are not inherited from ones parents. Rather, they are acquired de novo when certain sequences of genetic code fail to copy properly. Acquisition of CNVs is unpredicted, random, and spontaneous. Smaller variants are probably very common—each one of us may have one or two.

A raft of studies over the last five-years has propelled CNVs to the forefront of mental health research. CNVs have been linked with a number of disorders including Alzheimer’s (e.g. Rovelet-Lecrux, 2006), autism (e.g. Sebat et al. 2007), bipolar disorder (e.g. Lachman, 2007), and schizophrenia (e.g. Walsh, 2008). The broad theme of these association studies is that individuals with these disorders have more CNVs than the general population. As such, CNVs may be a major causal factor in cognitive (and other) illness.

What is the evidence?

Currently, there is not a great deal of evidence to support Crespi’s hypothesis. A 2008 Nature review paper by Cook & Schere, highlights two genomic loci particularly associated with both: 15q11 – 15q13 and 22q11. However, these are also associated with other disorders including mental retardation. Similarly, there are many loci associated with schizophrenia and not autism and vice-versa. These findings are not a fatal blow to Crespi’s hypothesis, but do recommend a certain level of skepticism.

Crespi also invokes behavioral (phenotypic) evidence, noting that these disorders have similar symptoms, which manifest in opposite directions. Language, social skills, etc., the hypothesis states, are underdeveloped in autistic-spectrum conditions and overdeveloped on the psychotic spectrum. Again, I am not convinced that there is sufficient evidence to substantiate these claims. Crespi points out that glutamate, the brain’s main neurotransmitter, is deficient in schizophrenia and overactive in autism. However, glutamate is associated with a myriad of disorders. Conversely, many biochemicals are associated with schizophrenia and autism.

Professor Jeffrey Lieberman discusses the glutamate hypothesis of schizophrenia.

To Conclude..

Crespi’s hypothesis is interesting and certainly worthy of further comment. Right now, the evidence is not there to substantiate the hypothesis, but that is not to write it off entirely. As genomic technology becomes more powerful, it is increasingly likely that it will be used to inform how we think about diagnosis and psychiatric disorders. Psychologists are compelled to take note of developments in molecular biology, and the two communities are beginning to merge in places. I suspect we will be seeing many papers of this kind in the next few years.

Read more…

G2C Online, schizophrenia resources:

• http://www.g2conline.org/#Schizophrenia

G2C Online, autism resources:

• http://www.g2conline.org/#Autism

CSHL Harbor Transcript article on CNVs (written by me!):

• http://www.cshl.edu/public/HT/pdfs/07_summer_autism.pdf

A review from Science magazine:

• http://www.sciencemag.org/cgi/content/full/324/5924/162b?rss=1