First published 6/06/11 on The Doctor Weighs In
If I had to choose the area of medicine most difficult to unravel it would be psychiatric disease, and specifically schizophrenia and Autism Spectrum Disorder, or ASD. The difficulties are enormous; the causes can be environmental, genetic, or both: the diseases are multi genetic; the affected organ, the brain, is extraordinarily complex and largely unknown, and the psychiatric manifestations can range from barely noticeable to overwhelmingly disabling. Unless we understand these diseases on the molecular level therapy will be a hit and miss affair.
A paper in Nature magazine (26 May 2011) made a significant advance in understanding Autism. Daniel Geschwind of UCLA and post doctoral fellow Irina Voineagu, and their colleagues, asked a seemingly simple question: are the genes in the autistic brain expressed differently from those of a normal brain?
They analyzed post-mortem brain tissue samples from 19 autism cases and 17 controls. They concentrated on over 500 genes expressed in the cerebral cortex, specifically in the frontal cortex and in the temporal lobe. They selected those areas because previous studies on autism had shown structural abnormalities there. .Important to note: the cerebral cortex’s frontal lobe plays a role in judgment, creativity, emotions and speech, and the temporal lobes regulates hearing, language and the processing and interpreting of sounds.
What they found was quite amazing. In normal brains there was a marked difference in gene expression between the frontal and temporal lobes. This difference has been known to develop in the embryonic stage. In the autistic brains, on the other hand, there was no difference between the two areas, the frontal lobe was indistinguishable from the temporal lobe –a finding that suggests that whatever the cause of the disease, be it genetic or environmental, it results in a defect in the embryo’s brain development.
They further analyzed their data and uncovered two other patterns of differences between normal and autistic brains. There was a big drop in the expression of genes that control neuronal function and communication in the autistic brain. This finding makes intuitive sense.
The other finding is baffling: the autistic brain showed a sharp increase in the expression of genes controlling the immune function and inflammation. Is it possible that part of the pathology of autism includes brain inflammation or some other immune reaction? The authors promise to follow up on this unexpected finding.
In short, this is the first study that points us toward a mechanism of the disease. Which, in turn is an absolute requirement for designing a rational approach to therapy.
Dov Michaeli, MD, PhD is a basic researcher, writing at The Doctor Weighs In.