Submitted but not published: no reasons given 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)

1. 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

2. 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

3. Teratology 1980, 22:71-75. 20.!
7- Decreased birth weight in infants of alcoholic women who
abstained during pregnancy.
Little RE, Streissguth AP, Barr HM, Herman CS: J Pediatr 1980,
96:974-977.
8-Paternal effects of ethanol in the Long-Evans rat. Mankes RF,
LeFevre R, Benitz KF, Rosenblum I, Bates H, Walker AI, Abraham R,
Rockwood W: J Toxicol Environ Health 1982, 10:871-878.
9- Learning achievement in sons of alcoholics. Hegedus AM,
Alterman AI, Tarter RE Alcohol Clin Exp Res 1984, 8:330-333. 61
10-Fetal alcohol effects in long- and short-sleep mice: activity,
passive avoidance, and in utero ethanol levels. Gilliam DM, Stilman
A, Dudek BC, Riley EP: Neurotoxicol Teratol 1987, 9:349-357. 21.
11- Fatherʼs drinking and infant birth weight: report of an association.
Little RE, Sing CF: Teratology 1987, 36:59-65. 60
12- Two generations of maternal alcohol consumption in mice: effect
on pregnancy outcome. Becker HC, Randall CL: Alcohol Clin Exp Res
1987, 11:240-242.
13-Maternal genetic effects on ethanol teratogenesis and dominance
of relative embryonic resistance to malformations. Gilliam DM,
Irtenkauf KT:
Alcohol Clin Exp Res 1990, 14:539-545.
14- Ethanol consumption inhibits fetal DNA methylation in mice:
implications for the fetal alcohol syndrome. Garro AJ, McBeth DL,
Lima V, Lieber CS: Alcohol Clin Exp Res 1991, 15:395-398.
15- Understanding the Occurrence of Secondary Disabilities in
Clients with Fetal Alcohol Syndrome [FAS] and Fetal Alcohol Effects
[FAE]. Final Report, August 1996., Streissguth et.al., Fetal Alcohol
and Drug Unit, University of Washington, Seattle, U.S.A.
16-Incidence of fetal alcohol syndrome and prevalence of alcohol-
related
neurodevelopmental disorder. Sampson PD, Streissguth AP,
Bookstein FL, Little RE, Clarren SK, Dehaene P, Hanson JW,
Graham JM Jr: Teratology 1997, 56:317-326.
17- Association of prenatal alcohol exposure with behavioral and
learning problems in early adolescence. Olson HC, Streissguth AP,
Sampson PD, Barr HM, Bookstein FL, Thiede K:
J Am Acad Child Adolesc Psychiatry 1997, 36:1187-1194.

4. 18- Mental Illness in Adults With Fetal Alcohol Syndrome or Fetal
Alcohol Effects. Chris. Famy et.al., Am. J. Psychiatry 1998; 155: 552-
554
19-Comparison of Social Abilities of Children with FAS to Those
Children with Similar IQ Scores and Normal Controls. Thomas et al
Alcoholism; Clinical and Experimental Research, 22[2],1998
20-Comorbidity Between Abuse of an Adult and DSM-III-R Mental
Disorders: Evidence From an Epidemiological Study Kirstie K.
Danielson, Terrie E. Moffitt, Ph.D., Avshalom Caspi, Ph.D., and Phil
A. Silva, Ph.D. (Am J Psychiatry 1998; 155:131–133)
21- Epigenetic reprogramming in mammalian development. Science
Reik W, Dean W, Walter 2001, 293:1089-1093.
22- Teratogenic Effects of Alcohol on Brain and Behavior. Sarah N.
Mattson et.al. Alcohol Research and Health. Vol 25 No 3, 2001
23- Comparison of the Adaptive Functioning of Children Prenatally
Exposed to Alcohol to
a Nonexposed Clinical Sample. Whaley et al. 25[7], July 2001.
24- Prenatal alcohol exposure and childhood behavior at age 6 to 7
years: 1, dose -response effect, B.Sood et.al., Pediatrics, 2001
Aug;108[2]; E34.
25- Clinical Implications of a Link Between Fetal Alcohol Spectrum
Disorder and Attention- Deficit Hyperactivity Disorder. Kieran D Oʼ
Mally, Jo Nanson, Can. J Psychiatry, Vol.47, No4, May 2002.
26-The Integration of Neurology, Psychiatry, Joseph B. Martin, M.D.,
Ph.D.Neuroscience in the 21st Century(Am J Psychiatry 2002;
159:695–704)
27-Paternal alcohol exposure affects sperm cytosine
methyltransferase messenger RNA levels. Bielawski DM, Zaher FM,
Svinarich DM, Abel EL: Alcohol Clin Exp Res 2002, 26:347-351.
28- Youth with Comorbid Disorders, Kieran D. Oʼ Mally, The
Handbook of Child and Adolescent Systems of Care, Chapter
Thirteen, 2003
29- Fetal Alcohol Spectrum Disorder [FASD]: A Need for Closer
Examination by the Criminal Justice System. Timothy E. Moore,
Melvyn Green. Criminal Reports, Vol 19 Part 1, July 2004
30- Fetal Alcohol Spectrum Disorder [ FASD ], Public Health Agency
of Canada, Cat.No. H124-4/2004, ISBN 0-662-68619-5, Publication
No. 4200

5. 31-- Report on Prenatal Exposure to Alcohol. Professor Peter
Hepper, Belfast, N. Ireland,1998.
32-Maternal alcohol consumption during pregnancy may delay the
development of spontaneous fetal startle behavior. Peter G. Hepper
et.a., Physiology and Behavior, 83 [2005], 711-714.
33-Fetal Alcohol Spectrum Disorders: An Overview with Emphasis on
Changes in Brain and Behavior EDWARD P. RILEY1 AND CHRISTIE
L. MCGEE Department of Psychology and the Center for Behavioral
Teratology, San Diego State University, San Diego, 2005
34- Binge Drinking During Pregnancy as a Predictor of Psychiatric
Disorders on the Sructured Clinical Interview for DSM-IV in Yourng
Adult Offspring., Helen M. Barr et.a.l., American Journal of
Psychiatry, 2006: 161: 1061- 1065
35- Metabolic and genetic factors contributing to alcohol induced
effects and fetal alcohol syndrome. Gemma S, Vichi S, Testai E:
Neurosci Biobehav Re 2007, 31:221-229.
36-Through the Lens of a Child Psychiatrist: The Need to Distinguish
FASD from other Neurodevelopmental Disorders in the DSM-V By
Susan D. Rich, MD, MPH iceberg june 2008
37-Fetal Alcohol Spectrum Disorders: The Epigenetic Perspective.
Philip C Haycock BOR Papers in Press. Published on May 27, 2009.
The Society for the Study of Reproduction
38-Ethanol teratogenesis in five inbred strains of mice. Downing C,
Balderrama-Durbin C, Broncucia H, Gilliam D, Johnson Alcohol Clin
Exp Res, 2009, 33:1238-1245. 19.!
39- Foetal alcohol spectrum disorders and alterations in brain and
behaviour. Guerri C, Bazinet A, Riley EP: Alcohol Alcohol 2009,
44:108-114.
40-Alcohol exposure alters DNA methylation profiles in mouse
embryos at early neurulation. Liu Y, Balaraman Y, Wang G, Nephew
KP, Zhou FC: Epigenetics 2009, 4:500-511.
41-Effect of alcohol consumption on CpG methylation in the
differentially methylated regions of H19 and IG-DMR in male
gametes: implications for fetal alcohol spectrum disorders.
Ouko LA, Shantikumar K, Knezovich J, Haycock P, Schnugh DJ,
Ramsay M: Alcohol Clin Exp Res 2009, 33:1615-1627.
42-Aspects of Fetal Learning and Memory, Dirix, CEH, and Nij
(Maastricht University Medical Centre), Jongsma, HW (University

6. Medical Centre St. Radboud), and Hornstra, G (Ma University
Medical Centre). Child Development, Vol. 80, Issue 4, 2009
43-Genetics and epigenetic insights into fetal alcohol spectrum
disorders, Michele
Ramsay, Genome Medicine, 2010, 2.27
44- NIAAA Home > Publications Teratogenic Effects of Alcohol on
Brain and Behavior Sarah N. Mattson Ph. D. ; Amy M. Schoenfeld;
and Edward P. Riley, Ph. D. University, San Diego.
45- NIAAA Home > Publications Effects of Prenatal Alcohol Exposure
on Executive Functioning Piyadasa W. Kodituwakku, Ph. D, Wendy
Kalberg, M. A. , and Philip A. May, Ph. D
46-Roy Eyal, MD,
American Academy of Child & Adolescent Psychiatry (AACAP) 56th
Annual Meetin