Submitted but not published 28th. May, 2010. The Editor, J.A.M.A. Dear Sir/Ms. Re. Rethinking Mental Illness. Thomas R. Insel; Philip S.Wang. JAMA. 2010;303(19):1970-1971 (doi:10.1001/jama.2010.555) This commentary will surely prove to be an historical event, in as much as it has been written by two psychiatrists. The fact is however that the connection between mental illness and complex cognitive and behavioral disabilities was made as long ago as 1996. Following the description of Fetal Alcohol Syndrome in the Lancet, 1973 a long term study was initiated by Streissguth et. al. The study showed that 95% of those diagnosed FAS/FAE [ FASD ] would subsequently receive diagnoses from the DSM, often multiple. In my experience it is not uncommon for the number of diagnoses to be four, or more on occasions. The striking connection between FASD and mental health has largely been ignored by the psychiatric community. A personal review of the American Journal of Psychiatry, January, 1996 to September, 2007 found only one title referring to FASD, representing approximately 0.08 per cent of all articles published in that time. A similar review of the Canadian Journal of Psychiatry, February, 1996 to October, 2007 also found only one title referring to FASD, representing approximately 0.03 per cent of all articles published in that time. Others have demonstrated the lack of interest and knowledge of FASD by the psychiatric community. With the rapid development of epigenetics it is now apparent that alcohol is a major cause of changes of gene expression. It plays its role at preconception, preimplantation and gastrulation, as it does through out the pregnancy. The epigenetic effect of alcohol applies to males and females and

may be passed on to future generations. As the commentary states, many environmental factors contribute to changes in gene expression e.g. famine, abuse, neglect. When we combine the direct impact of alcohol on genes with its wider cause of domestic violence and neglect, for example, the true contribution of alcohol to mental illness can be clearly seen. As the authors of the Commentary state - “ But first, it is time to rethink mental disorders, recognizing that these are disorders of brain circuits likely caused by developmental processes shaped by a complex interplay of genetics and experience.” The first step to rethinking mental illness is to understand FASD. Surely the day will come when the genes that control individual aspects of brain function will be identified. Changes in gene expression will be related to clinical presentations, such as those in the DSM. The generation at which the changes in gene expression occurred will be determined. The agent that caused the change [ with other environmental factors, in some cases ] will be identified. Then we will understand to what degree alcohol has determined the nature of mental illness. Barry Stanley REFERENCES 1- The Stream of Consciousness. William James. Psychology, Chapter XI 1892. 2- W.C. Sullivan, Stewart Scholar. A Note on the Influence of Maternal Inebriety on the Offspring. Journal of Mental Science. 1899. 3-Stockard CR: The effect on the offspring of intoxicating the male parent and the transmssion of the defects to subsequent generations. Am Nat 1913, 47:641-682. 5 4- Pattern Of Malformations in Offspring Of Chronic Alcoholic Mothers, Jones et.al. The Lancet: Saturday 9 June 1973 5- The Effects of Drinking on Offspring; An Historical Survey of American British Literature. Rebecca Warner, Henry L. Rosett. The Journal of Alcohol Studies. 1975. 6-The fetal alcohol syndrome in mice: maternal variables. Chernoff

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