Saturday, March 31, 2012

Reasons for the increased incidence of autism (and other brain disorders)

The reasons for the increased incidence of autism and other disorders are two-fold: on the one hand we have increased awareness and diagnosis, on the other hand we have a genuine increase in the incidence of disease.

The genuine increased incidence of disease is due to three factors: age, quantity and fit. Age refers to older parents, in which there is increased incidence of DNA mutations in spermatocytes and oocytes. Over 80% of the genes in the genome are involved in brain function, providing plenty of targets in which random mutations can occur that may affect brain function. Quantity refers to increased environmental exposure to factors that affect brain development and growth, including for autism possible chemicals in the environment and nutritional factors that promote a diabetes-like state in mother and fetus. Fit refers to the fact that there is an increased preservation and selection in the population of gene variants involved in mental functions, which are the same gene variants that, if you have too many of them, in the wrong combination and in the wrong environment, can lead to psychiatric disorders such as autism, schizophrenia or bipolar disorder (what we call in our group the 4C x E model of disease- contextual cumulative combinatorics of common gene variants and environment).

Our best estimate so far, is that autism is a disease of connectivity, based on the body of evidence in the field, and comparative genomics of schizophrenia and autism (see for example Ayalew, Le-Niculescu et al. Molecular Psychiatry 2012 In Press). We think that autism is a disease of localized increased connectivity in the brain (abnormal or supra-normal), and overall decreased connectivity to the environment, hence the occasional very high levels of performance on specific tasks but overall social problems. Schizophrenia may have localized abnormal increased connectivity in certain brain circuits (leading to hallucinations, delusions and paranoia), but overall is characterized by much more decreased connectivity in the brain and with the environment, hence the occasional increased creativity but overall poor social functioning if left untreated.

The solution for both disorders is to modulate the age, quantity and fit factors. Parents should conceive at an earlier age or at least store their germinal cells in youth for later conception. Environmental factors that affect brain development and growth should be identified ( stress, inflammation, infections, head trauma, drugs, nutritional factors, chemical pollution), avoided and mitigated against with early preventative treatments. The continued increased selection and enrichment of genes involved in increased mental performance is unavoidable in our current information-driven era (where the brain is our main tool and reason for professional success), but genetic testing for possible early intervention, coupled with brain exercises and better treatments to minimize the deficits, and a greater appreciation and tolerance for diversity and specific skill sets, should make most individuals into content and productive members of society!

Alexander B. Niculescu, MD, PhD