Research evolution
That genetics makes up the largest portion of autism research is probably no surprise. What may be unexpected news is that a number of other subfields — including immune function, oxidative stress and toxin exposures — are growing even faster, according to a new meta-analysis published in Molecular Psychiatry.
By contrast, the number of papers published on theory of mind and neuropathology has slowed.
Genetics is the biggest winner by far: The number of papers published in genetics (pink) is almost equal to all other areas combined and is 2.4 times that of the next largest subfield, neuroimaging (turquoise). The increase in genetics and neuroimaging research is likely to be the result of the rapid advances in technologies in these fields. The drop in neuropathology (orange) research may be due to the lack of available postmortem tissue.
The analysis is biased, of course, based on the categories the scientists picked to analyze. In this case, they focused specifically on what they call “physiological abnormalities” related to autism.
The researchers searched the literature from 1971 to 2010 in four defined categories — immune dysregulation or inflammation (blue), oxidative stress (red), mitochondrial dysfunction (green) and environmental toxicant exposures (purple) — as well as four broader categories of genetics, neuroimaging, theory of mind (light blue) and neuropathology.
But they did not search for studies related to more molecular topics, such as signaling through synapses, the junctions between neurons, or neural circuits, both growing areas of study in autism.
According to the analysis, research on the immune system’s role in autism began growing in the 1990s, while research on oxidative stress and toxic exposure picked up speed over just the past ten years. The number of studies on mitochondrial dysfunction showed the most recent bump, increasing significantly from 2006 to 2010 after a relatively flat period.
It’s not clear why research on theory of mind deficits in autism has begun to fall. In general, autism research funding is focusing more specifically on causes of autism, including genetic and environmental factors, rather than on its manifestations.
According to a 2010 analysis of National Institutes of Health funding for autism research in 2009, led by the Interagency Autism Coordinating Committee, the largest portion of research funding was directed at identifying the cause of the disorder. Within that area, research identifying genetic factors for autism garnered 50 percent of funding.
Genetics is likely to retain its status as a heavy hitter, but judging from this analysis, the newer players may also soon grab a significant piece of the pie.
Comments
Forgive me for being a bit stupid, but the graphs don't appear to bear much relation to the text.
Neuropathy (orange) is declining as you say, but I can't see any evidence that theory of mind research is declining. After 1986, all of the other lines are only increasing.
Also, what does "Proportion of total studies" mean? For the most recent period, the proportions add up to almost 300%. Does this mean that most studies fell into multiple categories. As the total "proportion of total studies" increases year on year, does that mean that research is becoming increasingly cross-disciplinary?
Finally (sorry), any idea why they only looked at "theory of mind" as a non-biological research category? It's very sad if the authors think that this is the only cognitive research worth considering. And for that matter, why didn't they consider intervention research?
Thanks for your comments. According to the paper, the second graph shows "The proportion of publications within each research area normalized by the total number of publications within the specific research area. This allows the relative growth in each research area to be observed."
Theory of mind research has declined in relation to other types of autism research. I'm not sure why the authors chose to look at theory of mind but not other types of cognitive research.
Immune deficiencies, mitochondrial dysfunction, genetics, unfavorable pre, peri and neonatal events, the connectivity theory in autism, synaptic signaling, damaged circuitry in the forebrain, neuropathology, the association of common variants in COMT gene with the broader autism phenotype and Molina’s discovery that 22q11 sperm deletions and duplications are present in all males can all be found in studying the Di George/velo-cardio-facial (22q11 deletion syndrome).
http://www.ncbi.nlm.nih.gov/books/NBK1523/
93% of 22q11 deletion syndrome cases are caused by de novo mutations in contrast with being an inherited event.
77% of 22q11 patients have an immune deficiency regardless of clinical presentation.
In a series of 100 consecutively referred patients with the 22q11 deletion syndrome who underwent extensive psychological testing, 23% were diagnosed with the broader definition ASD and 5% were diagnosed with narrowly defined autistic disorder. The presence of broadly defined or narrowly defined autism in the 22q11 deletion syndrome is 25 times greater than the prevalence of broadly or narrowly defined autism in the general population.
The 22q11.2 region harbors the COMT gene and common polymorphisms in the COMT gene is associated in general population studies with the broader autism phenotype in self-reported schizotypal personality in healthy males, anxiety related traits, OCD and panic disorder without the 22q11.2 deletion syndrome.
Meechan et al also found ’ Six genes in the 1.5 MB region of chromosome 22 deleted in DiGeorge/22q11 Deletion Syndrome—Mrpl40, Prodh, Slc25a1, Txnrd2, T10, and Zdhhc8—encode mitochondrial proteins. All six genes are expressed in the brain, and maximal expression coincides with peak forebrain synaptogenesis shortly after birth. Furthermore, their protein products are associated with brain mitochondria, including those in synaptic terminals’ and ‘ Our results suggest that altered dosage of one, or several 22q11 mitochondrial genes, particularly during early postnatal cortical development, may disrupt neuronal metabolism or synaptic signaling’.
Molina et al (2011) studied sperm mutations in healthy male volunteer donors focusing on three mutations identified in individuals with a genetic autism syndrome. The three sperm mutations that were specifically examined were: 7q11.23 (Williams Syndrome), 15q11-13 (Prader-Willi Syndrome), Di George/velo-cardio-facial (22q11 deletion syndrome) and almost all genetic and epigenetic cases of Williams Syndrome, Prader-Willi Syndrome and 22q11 deletion Syndrome are de novo mutations in contrast to being inherited events. All three sperm mutations (deletions and duplications) including 22q11 sperm mutations were sporadically found in the sperm of all the volunteer donors and the rate of 22q11 sperm mutations in volunteer donors were consistent with population prevalence of the 22q11 deletion syndrome (1 in 4000).
References
Molina et al (2011). Sperm rates of 7q11.23, 15q11q13 and 22q11.2 deletions and duplications: a FISH approach. Hum Genet. 2011 Jan;129(1):35-44. Epub 2010 Oct 8.
http://www.ncbi.nlm.nih.gov/pubmed/20931230
Meechan et al (2008). Mitochondrial localization and function of a subset of 22q11 deletion syndrome candidate genes. Moll Cell Neurosci. 2008 Nov39(3) 439-51
http://www.ncbi.nlm.nih.gov/pubmed/18775783
Niklasson et al (2009). Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Rev Dev Disab. 2009 Jul-Aug;30(4):763-73. Epub 2008 Dec 13.
http://www.ncbi.nlm.nih.gov/pubmed/19070990
Theory of mind places the onus on the individual, much like Bettleheim's poisonous mothers. They are evil because they don't care.
To look at possible biological causes of behavior, one has to see the individuals ability to become an overcomer, despite the crippling manifestations of disease/damage.
Would you rather be brain damaged, or mentally ill?
Tough call...
This would carry more weight if Dan Rossignol, one of the paper's authors, was not also a leading proponent of the idea that oxidative stress is a cause of autism, with a significant commercial interest in promoting hyperbaric oxygen therapy as a cure. How much junk science by third rate researchers with something to sell was included in this review?
I thought the point about the authors' choice of categorization was pretty important. A person wouldn't write a paper like this if not to make a point. It's not like they've discovered a new element that just "is"; they've created these categories out of whole cloth to suit their purposes, and given that the lead author has something to sell which this analysis tends to legitimize, I really wonder whether the journal did all the checking it should have done before allowing its pages to be used as advertising.