GENETICS AND THE ENVIRONMENT
Dr. Julie Daniels, an Assistant Professor of Epidemiology and Maternal and Child Health at the University of North Carolina, wrote an editorial published in the July 2006 edition of Environmental Health Perspectives that is well worth reading. (Thanks to María Luján for bringing it to my attention.) Dr. Daniels notes that:
Speculation that the environment plays a role in the development of autism primarily comes from two observations: a) although concordance among monozygotic twins is high, it is not perfect, and a specific “autism gene” or set of genes has not yet been identified; and b) the prevalence of autism is higher than previously thought-if it is rising, the rise might be associated with a shift in the environment.
Dr. Daniels displays far more logic than one is accustomed to hearing in our little debates, when she writes that the confounding of causal research is the likely result that what we call ASD may result from a variety of gene-gene and gene-environment interactions. Although conceding that the “perception” of increased prevalence may result from changing diagnostic criteria or increased availability of diagnostic tools and services, she also acknowledges the possibility that we may be seeing a true increase in prevalence. There is little in the way of “systematically collected data in the same population over time that can be used to evaluate true prevalence rate trends.”
After stating that environmental factors could explain true shifts in prevalence, and further noting the difficulty in assigning causal based on ecologic associations, Dr. Daniels writes the following, which I partly agree with:
It is unlikely that one or even a few specific environmental agents are responsible for the majority of ASDs. It is more likely that some individuals have enhanced susceptibility to insults from the environment that may, in combination with their genetic predisposition, lead to autism. It is rarely possible to distinguish these complex relationships by simply evaluating trends in the general population.
The much publicized concern over vaccines and autism has primarily been based on such ecologic trends. More rigorous studies evaluating vaccine-related hypotheses are needed to incorporate individual-level exposure data, account for alternate exposures to metals, and evaluate susceptible subgroups of the population. However, attention should also be given to other environmental hypotheses.
Although I agree that environmental insults other than vaccines and thimerosal need to be considered, I think Dr. Daniels underestimates the probable connection of the single most pervasive exposure to a generation of children. Nevertheless, I am delighted that a respectable epidemiologist recognizes the limitations of the epidemiological evidence and is displaying an open mind on the question.
To state the obvious, I think the more we learn about the processes of autism, the more clear the causal connections will become. If well-designed research shows I am wrong in my opinions, I can live with it. What I can't stand, however, is the tendency of so many scientists to bury their heads in the sand. Dr. Daniels' willingness to follow where the science may lead is refreshing.
And that brings us to some exciting things going on in the study of neuroscience as it relates to autism. One of the most interesting presentations I saw at the Autism One Conference this past May was by Dr. Manuel Casanova, who has been researching the differences in minicolumns between brains of autistic individuals and neurotypical persons.
Ian Parker, takes a detailed but very readable look at Dr. Casanova's work, and reaches conclusions that sound consistent with what was reported at Autism One:
Reduced minicolumn width appears to be a prerequisite for autism. But, the reported minicolumn widths found within autistic brains are still within the normal distribution of minicolumnar width, albeit at the tail end (Casanova 2006). This suggests to me that the existence of narrow minicolumns is not enough by itself to result in an ASD diagnosis. The key instead appears to be a reduction in inhibition within minicolumns, rather than width alone. Reduced width increases the consequences of reduced inhibition, but does not automatically cause it. In effect, a brain with narrower minicolumns may be less robust, and therefore more vulnerable to the complications that could come with deviation from the narrow tolerances within which the brain functions. In a brain with wider minicolumns, a loss of inhibition would not have as significant an impact, as minicolumnar width (and therefore distance between minicolumn information processing cores) would still exist to reduce intercolumnal spill, and thalamic projections would result in fewer minicolumns per macrocolumn to be affected.
Even with reduced minicolumn width, a “second hit” is required for there to be a manifestation of dysfunctional autistic symptoms. Ian's conclusion suggests that the notions of a cure and maintaining neurodiversity may not be mutually exclusive. Read it here. (The conversation taking place in the comments will make your investment of time doubly worthwhile.)