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1) Lawyers Prepare For 100 Jab Cases
LAWYERS MET at the High Court in London yesterday to prepare for the forthcoming legal battle over the controversial jab against measles, mumps and rubella.
After the Government's announcement that alternatives to the triple vaccine have been banned, solicitors and counsel dealt with preliminary procedural issues at a private meeting before John Ungley, Master of the Supreme Court.
The group action, involving some 100 parents who claim their children were permanently damaged by the MMR jab, will eventually go to a full hearing before a High Court judge. It is estimated that as many...........Go to Yahoo Go to Yahoo
2)....Long Term, Live-in Care- can it survive or will the DTI put the companies who
provide such care out of business?
The DTI are planning to introduce amendments to existing employment legislation that will have a devastating affect on many older and disabled people receiving live in care at home.
Those "hit the hardest" will be disabled people supported by the financial system of Direct Payments, or by Personal Injury Claim Settlements and elderly people who can currently afford to pay for their care from their own resources. Their costs will rise by over 50% per annum. The VAT could rise from a current minimum of £6.13 per week to as high as, in one instance, £132.21 - a twenty one fold increase.
Ministers and Officials at the DTI are determined to drive through their proposals..........See Web Page:- WWW.care-gb.com
AUTISM MMR LINK
MMR Vaccine and Autism : No Epidemiological Evidence for A Causal Association
Taylor B. Miller E. Farringdon P.C. Petropolous M.C. Favot-Mayaud I.Li J. & Waight A.
The above paper, published in the Lancet on Friday 11th June 1999, was funded by the Medicines Control Agency and authored by the Department of Community Child Health Royal Free and University College Medical School, London, together with The Public Health Laboratory Service.
Details appear to have been substantially leaked by the authors prior to publication.
THIS IS THE FIRST PUBLIC ADMISSION BY THE GOVERNMENT OF THE MASSIVE INCREASE IN AUTISM. IT WOULD, HOWEVER, APPEAR TO BE A CYNICAL ATTEMPT TO DISGUISE THE TRUTH. SHOULD THIS BE THE CASE THEN WHAT WE FACE IS A SCANDALOUS PUBLIC DUPE OF BSE PROPORTIONS.
SUMMARY OF STUDY
The study is a case series analysis, a weak form of epidemiological analysis which can only suggest or refute very large relationships. The authors begin by admitting the intrinsic flaws in the available data whilst clarifying the aim of the study as to look for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of the MMR vaccine.
The most significant finding of the study is that the number of children with autism has risen by 25%, year on year compounded since the introduction of MMR.
Additionally a significant temporal clustering for the onset of parental concern about their child's behaviour was found within six months of the MMR vaccine.
Astonishingly, despite these clear findings, the interpretation of the study is that the analyses do not support a causal association between MMR vaccine and autism.
Alarmingly the reader may easily be misled into believing that the rise in autism predates MMR introduction whereas the study the demonstrates a potential association. Credit= Allergy induced Autism end
Breaking news - A controlled clinical trial of secretin SYNTHETIC HUMAN SECRETIN in children with autism or PDD reports that secretin has no more effect than a placebo.
A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SYNTHETIC HUMAN SECRETIN IN THE TREATMENT OF AUTISM AND PERVASIVE DEVELOPMENTAL DISORDER (PDD) (Credit=Autism Society of Alabama)
Measles vaccine 'link to autism in children'
Credit The Independent
By Andrew Laing
9 April 2000
British scientists have uncovered new evidence suggesting a link between the MMR vaccine and chronic illness in children, including autism.
Their research, presented to the US congress last Thursday, points to the presence of the measles virus in the gut of 24 out of 25 autistic children.
The virus is one of the elements in the combined mumps, measles and rubella vaccine routinely administered to hundreds of thousands of children in the UK.
Congressmen were told that there was "compelling evidence" of an association between infection by the measle virus and autism in the children, many of whom appeared to have developed the condition after they had been injected with the triple vaccine.
go to: http://www.independent.co.uk/news/UK/Health/2000-04/measles090400.shtml
The Independent http://www.independent.co.uk/news
SOURCE: American Journal of Human Genetics 2001;69.
National Institute of Child Health and Human Development
FOR IMMEDIATE RELEASE
Tuesday, August 21, 2001
|
Contact: Melissa Braddock or Robert Bock
(301) 496-5133 |
Researchers Find New Insights Into the Genetic Foundations Of Autism
In collaboration with their European colleagues, scientists funded by the National Institutes of Health (NIH) have come one step closer to determining the genetic basis for autism. The researchers have identified regions of four chromosomes that appear to be linked with the disorder.
"These findings confirm the role of genetics in autism and are a major step in narrowing the search for the specific genes involved," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development (NICHD) and co-chair of NIH's Autism Coordinating Committee.
At least one in 500 people are affected by some form of autism, a neurodevelopmental disorder that causes problems with communication and social interaction, as well as repetitive actions and interests. Earlier studies with families and twins have shown that there is likely to be a strong inherited component to autism. Because of the wide range of patients' symptoms, many researchers suspect the disorder is the result of a complex interaction between several different genes involved with brain signaling and development. Unidentified environmental factors are also likely to play a role.
In this study, researchers screened the DNA of more than 150 pairs of siblings with autism. They found extremely strong evidence that two regions on chromosomes 2 and 7 contain genes that are involved with autism. Likely locations for autism-related genes were also found on chromosomes 16 and 17, although the strength of the correlation was somewhat weaker. The findings will appear in the September issue of the American Journal of Human Genetics.
Chromosome 7 is known to be associated with many language disorders and has been shown to be linked with autism in some earlier studies, but not all.
"Because of the size of this study and the strength of the correlation found, there is now little doubt that the so-called language disorder chromosome is significantly involved with the development of autism," said Marie Bristol-Power, Ph.D., NICHD Special Assistant for Autism.
Researchers were particularly excited by evidence of an autism link on chromosome 2, since this area had recently been identified by another, independent research group. NICHD is currently supporting a range of research looking at the interaction between the genes for early brain development located on chromosome 2 and environmental influences.
"We wouldn't be looking for genes on chromosome 2 if not for these findings. Now we can be fairly certain that genes on chromosomes 2 and 7 are linked with autism," said Dr. Ed Cook from the University of Chicago, a participating researcher on the project.
Dr. Bristol-Power noted that the project's international scope was critical in getting a sufficiently large number of patients who were diagnosed using the same methods. Drawing DNA from a large number of people allows researchers to make more definitive claims of linkage between the DNA region and the disease.
"Teams from all over the world worked together to produce this result," said Dr. Bristol-Power. "This kind of collaboration is how the problem of autism will eventually get solved. Even larger numbers, 400-500 pairs of relatives, are needed to get more definitive answers, and collaborative international efforts to complete a genome scan on such numbers are now underway."
This work was carried out by members of the International Molecular Genetic Study of Autism Consortium, a group of clinicians and scientists from the UK, USA, France, the Netherlands, Denmark, Italy, and Greece. (For more information, see website http://www.well.ox.ac.uk/~maestrin/iat.html.) The US component of their work was conducted as a part of the Yale/University of Chicago/UCLA Collaborative Program of Excellence in Autism (CPEA), part of the Network on the Neurobiology and Genetics of Autism, a research initiative funded by NICHD and the National Institute on Deafness and Other Communication Disorders.
"It is encouraging to know that so many investigators in the consortium are working together for so many years to accomplish the goals of adding to our understanding of the causes of autism," said Dr. Cook. "It is even more encouraging to know how many outstanding investigators in other research groups, including other members of the CPEA, are now focusing their talents on this often devastating illness. Most importantly, none of this would be moving forward without the outstanding participation of families of individuals with autism."
Researchers currently know little about what is going wrong in the brains of autistic children, and they hope to gain answers by locating the specific genes involved and understanding their functions.
"We will continue to search for the individual genes which are linked with the development of autism," said Dr. Fred Volkmar of the Yale Child Study Center. "Knowledge of the genes will lead us to better, earlier diagnoses and interventions and, ultimately, better treatment options."
This work has been funded by the U.K. Medical Research Council, The Wellcome Trust, BIOMED 2 (grant CT-97-2759), EC Fifth Framework (grant QLG2-CT-1999-0094), Telethon-Italy (grant E.1007), the Janus Korczak Foundation, Deutsche Forschungsgemeinschaft, Fondation France Télécom, Conseil Régional Midi-Pyrénées, Danish Medical Research Council, Sofiefonden, the Beatrice Surovell Haskells Fund for Child Mental Health Research of Copenhagen, the Danish Natural Science Research Council (grant 9802210), the National Institute of Child Health and Development (grant 5-P01-HD-35482), and two other NIH Institutes, the National Institute of Mental Health (grants NIH K05 MH01196 and K02 MH01389) and the National Center for Research Resources (grant MO1 RR06022 GCRC NIH).
The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD website, http://www.nichd.nih.gov, or from the NICHD Clearinghouse, 1-800-370-2943; E-mail NICHDClearinghouse@mail.nih.gov. end
Scientists Home in on Sites for 'Autism Genes'
Reuters
Wednesday, August 22, 2001
NEW YORK, Aug 21 (Reuters Health) - Scientists have identified regions on four chromosomes that appear to be associated with autism.
"These findings confirm the role of genetics in autism and are a major step in narrowing the search for the specific genes involved," Dr. Duane Alexander said in a prepared statement. Alexander is the director of the National Institute of Child Health and Human Development (NICHD) and co-chair of the National Institutes of Health's Autism Coordinating Committee.
Autism is characterized by difficulty with communication and other social interactions, as well as repetitive, stereotyped patterns of activities and interests. Past studies of twins and families have suggested that genetics played some role in autism, but no specific genes have been linked to the disorder.
To conduct the research, members of the International Molecular Genetic Study of Autism Consortium--including researchers from the US, UK, France, the Netherlands, Denmark, Italy and Greece--screened DNA from 152 pairs of siblings with autism.
Evidence for a link between autism and two regions--one each on chromosomes 2 and 7--was very strong, according to the report in the September issue of the American Journal of Human Genetics.
A weaker link was found with regions on chromosomes 16 and 17.
Past studies have linked areas on chromosomes 2, 7 and 16 with autism. Chromosome 7 is also associated with several language disorders.
International efforts are now under way to screen the DNA of 400 to 500 pairs of relatives with autism to come up with more definitive answers, said Dr. Marie Bristol-Power, the NICHD's special assistant for autism. end
Can the Autistic Become Non-autistic?
By Don Partridge, Naturopath
Dr. Kathryn Dykman, MD, recently presented her findings on Autism and Nutraceuticals at the Annual Meeting of the Pavlovian Society, Dusseldorf, Germany. Her full report has been peer-reviewed, and will be published in the Integrative Physiological and Behavioral Science, the Official Journal of the Pavlovian Society (JIPBS). Her papers on Chronic Fatigue/Fibromyalgia and on Autism were judged the best overall! Dr. Dykman's paper on autism was entitled "Changes of Health in Children With Autism."
Did you know that autism affects one in every 500-1000 children today? That is a dramatic increase from years past. Chances are you know someone who has an autistic child. It is as common as many childhood diseases like leukemia and juvenile diabetes. Only 5-10% EVER become independent. Let's say that again: only 5-10% are EVER able to totally care for themselves.
There are a number of causes, most prevalent is the thought that there is some sort of genetic link, or perhaps, something wrong with the neurotransmitters in the brain. There is known to be a significantly reduced number of T-cells and Natural Killer cells. (Are we surprised?) The medications have severe, even horrific side effects, including sedation, insomnia, hyperactivity, increased agitation, nightmares, bouts of unexplained screaming, and striking out physically at other people.
Dr. Dykman's study involved nine children ages three to seven years old who had all been diagnosed with autism. Seven of them were boys and two of them were girls. All were Caucasian. Each child was given one teaspoon of a patented, proprietary glyconutrient every day for three months.
On the official Scale of Autistic History form, 100% of the children had a decrease in scale height (meaning behavior and all improved)! 100% of the children remained at the same level of good health or improved. In other words, during that three-month time, NONE got worse.
In grading the severity of autism, practitioners use a scale of 15 parts. A score of less than 30 denotes a child without autism. A score of 30-37 is an autistic child, and a score of 37 or more is a severely autistic child. In the conservative language of science, she reported, "The mean scores on the CARS test decreased from 40 to 32." More exciting was her personal report: Seven of the nine children, during the three months of consuming the glyconutrient, CHANGED THEIR SCALE SCORE TO LESS THAN 30, in other words they are non-autistic! The other two decreased their scores from severe to moderate autism. Given more time, the results will be even more exciting!
Dr. Dykman then read us statements from the parents and the teachers of these children. It brought tears to my eyes. If you feel you need a real reason to get out there and tell hurting people about Mannatech products, this is it. (Both this study and the longitudinal CFAs study will be published in an upcoming issue of JIPBS).
Title: The Effects of Glyconutritional Supplementation on Autistic Children
Authors: Kathryn D. Dykman1 & Ray McKinley2 Address: Mannatech, Inc., Coppell, TX & Private Practice and Independent Mannatech Associates2, Detroit, MI, USA SOURCE: Published on the Proceedings of the Annual Meeting of the Pavlovian Society. Dusseldorf, Germany, October 30-Novem- ber 1, 1998
ABSTRACT:
Autism is a common Childhood disorder often misdiagnosed or not detected at the time parents report symptoms. Cardinal symptoms include a failure to relate socially and affectionate- ly to parents or others, language or speech impairment; compul- siveness often seen as a desire for sameness; and mental retard- ation. Nine autistic children were studied over a period of 3 months; all were placed an glyconutritional supplement for 3 months. Four rating scales were completed by parents prior to and after nutritional supplementation: Autism History and Parent rating scale, Wing Autistic Disorder Interview, Physical Health Evaluation Rating Form, and the Childhood Autism Scale (CARS}. Of these, the CARS is the best and provides cutoff scores; not autistic (scores <30), mild disorder (30-36), and severe disord- er (>36). Paired t-tests indicated that the children improved on all ratings; e.g., the mean scores on the CARS decreased from 40 to 32 during treatment (p<0.01). Teachers not aware of the re- search made the following comments: "His improvement is amazing; He is beginning to use single words again; He gets dizzy and falls down now when he tries to spin; He is now eating with a spoon; and he is able to solve problems." We recognize that there was no control for placebo in this first project and that this will be necessary in future projects.
Similar improvements are had in Cystic Fibrosis, ADD and ADHD, and other troubling childhood diseases. (Dr. Dykman's previous studies on Chronic Fatigue/Fibromyalgia and ADHD are available on MedLineT.) Do you know a suffering child that needs release from bondage?
For further information please contact: Gregg Hall
mannaglobal@baycomm.net
VACCINES.
05.11.97
The latest article about autoimmunity and autism is the following:
Circulating Autoantibodies to Neuronal and Glial Filament Proteins in Autism. Vijendra K. Singh, PhD, Reed Warren, PhD, Rex Averett, MS, and Mohammad Ghaziuddin, MD. Pediatric Neurology, Vol.17 No. 1 88-90, 1997.
"Increased occurrence of autoantibodies to neuron-axon filament protein (NAFP) and glial fibrillary acidic protein (GFAP) in many autistic subjects provides additional evidence for an autoimmune mechanism in a subset of autism."
end
Measles jabs suspected in autism cases.
by VICTORIA MACDONALD Health Correspondent
"© Telegraph Group Limited, London 1996"
THE Department or Health is under pressure to fund research into the safety of childhood vaccines, as evidence grows of a link between the injections and autism.
There have already been concerns about vaccines causing other forms of brain damage. Now one of the world’s leading experts on autism is backing parent groups in their demands for studies to be done on the vaccination risk.
Dr. Bernard Rimland, director of America’s Autism Research Institute. said the idea that vaccines could be causing the condition was unpopular with the medical establishment.
“But there is now no doubt in my mind that something serious is happening,” he said. ‘We have been surprised and dismayed that so little is known about the causes of autism.
“It is time to tackle this aggressively,” said Dr. Rimland, who was technical adviser on Rain Man, the film in which Dustin Hoffman portrayed an autistic man with a remarkable memory.
The number of autism cases is unclear, but is thought to be increasing. The National Autistic Society, which is launching Autism Awareness Week next week, said that this could be because there was more awareness of the condition, particularly since Rain Man,
The society would not be drawn on the possibility of a link between the condition and vaccines.
A class action being prepared by Dawbarns Solicitors on behalf of vaccine-damaged children includes 169 cases allegedly linked to the measles, mumps and rubella inoculations.
Kirsten Limb, of Dawbarns, said there had been a further 200 inquiries from parents who feared their children might have developed autism. The cases were all of severe atypical autism, in which the condition appeared to develop following vaccination.
Autism is a complex condition, believed to be caused by organic brain damage. Sufferers develop irrational fears and obsessions, and are often described as living in their own world.
It is It is generally believed that children are born with autism. However, in all the cases presented to Dawbarns the children had been developing normally until they had their vaccinations.
One theory is that the vaccine, particularly the measles part, causes encephalitis - swelling of the brain - that triggers autism. All the children with atypical autism also have Crohn’s disease, an inflammatory bowel disorder that has been linked with measles.
Rosemary Kessick, whose son William, aged eight, was finally diagnosed a year ago as autistic, said her child had been developing normally until he was vaccinated at 14 months. Then, from an infant who had started speaking, playing normally and making eye contact he became withdrawn, started headbanging was clumsy and unco-ordinated and lost the words he had learnt. He also had severe stomach pains and developed food intolerances.
Mrs. Kessick, from Peterborough, said it was “just not acceptable” that the authorities had failed to conduct research to prove or disprove a link with the vaccination. She said: “My son is beautiful. truly beautiful, but he cannot talk, he is hyperactive and incontinent.”
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JABS Newsletter Spring'97 from UK 1 of 2.
In 1988 three brands of MMR vaccines were introduced into the British vaccine programme, by September 1992 two had been withdrawn because the mumps component had caused 'mild mumps meningitis' in some children.
Since the JABS group was set up three years ago over 350 children have been reported to us with serious health problems following an MMR vaccination. Long term problems stated by parents include : Encephalitis ( inflammation of the brain ), epilepsy, severe learning difficulties, speech and communication problems, autism, chronic arthritis, Guillain-Barre syndrome, severe visual and hearing problems, post viral fatigue syndrome (M.E.), bowel problems and death.
In November 1994, 7 million schoolchildren aged 5-16 years were given an MR vaccine. The Department of Health has acknowledged 530 severe reactions following this campaign. Many of the families of the 530 children affected have contacted JABS. Long term problems reported after MR injections include: Encephalitis, epilepsy, memory loss, chronic arthritis, Guillain-Barre syndrome, severe visual and hearing problems, post viral fatigue syndrome (M.E.), Crohn's disease, Multiple Sclerosis, S.S.P.E. ( subacute sclerosing panencephalitis ), and death.
The Department of Health has now launched another MMR campaign this time for the pre-school children aged 3-6 years. Parents are again being told it is perfectly safe and can be given at the same time as the diphtheria/tetanus and polio booster. Four live viruses and two toxoids together whether the child needs them or not.
The Government's Department of Health accepts that vaccines can cause severe damage. There is a vaccine damage payment unit which has awarded hundreds of payments over the years to parents in respect of their vaccine damaged children. But our research indicates that only 2 in 80 applications are successful ( one-time payment for life of 30,000 English pounds ).
Given that severe vaccine damage can and does occur, no child should be exposed to a risk of vaccine damage if they are still immune to the disease from previous vaccination or earlier illness. Parents can request a simple blood test. The Department of Health states it is not cost effective to take blood samples to test for immunity.
Ray Gallup Gallup_r@stmisb.adm.stevens-tech.edu
MYELIN and AUTISM.
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Vaccines as a triggering agent - Autism and Autoimmunity.
Excerpts of Articles
Gupta S, Aggarwal S, Heads C. Brief Report: Dysregulated Immune System in Children with Autism: Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics. Journal of Autism and Developmental Disorders, Vol. 26, No. 4, 1996.
We theorized that the high titers of rubella antibody present in mothers of children with autism would be transplacentally transferred and may also persist for a prolonged period in the child. When such a child gets MMR immunization, rubella antigen may complex with preexisting antibodies and such complexes might play a role in the pathogenesis of autistic features.
Fudenberg H.H. Dialysable Lymphocyte Extract in Infantile Onset Autism: A Pilot Study. Biotherapy 9: 143-147, 1996.
Fifteen of the true autistic patients developed symptoms within a week after immunization with the measles, rubella and mumps vaccine (MMR); 3 had high fevers ( up to 106 degrees F. ) and convulsions within one day of administration; in the other 7 true autistic, the symptoms gradually worsened in severity ( e.g., gradual rather than sudden loss of vocabulary ) with onset of clinical abnormality beginning between 15 and 18 months of age.
In those patients, rubella immunization, as well as other live virus immunizations, should be delayed until at least 3 years of age, since cell mediated immunity in many children does not reach maturity at 15 months, the usual time of MMR administration. We observed 2 families, each with 3 children in whom 2 of the 3 suffered from autism. The incidence of viral infections, especially otitis media, was very high not in the non-affected sibling. In one family of identical autistic twins, one responded to therapy, the other did not. Thus, we contend that this syndrome occurs in congenitally predisposed individuals after exposure to a given virus, live virus immunization, or to DPT immunization at 4 weeks in those instances where the mother has a very high IgG antibody titer to, for example, tetanus toxin or diptheria toxin.
Indeed, the IgG antibody crosses the placenta during pregnancy and will be present in the infant who was given these toxins at 4 weeks of age thereby precipitating reaction and subsequent autism. We have observed several infants with pseudo-autistic syndrome who were given the DPT immunization at 4-6 weeks, convulsions occurred and were followed by steadily increasing autistic symptoms. Live rubella immunizations at 15 months has precipitated fever ( 106 degrees F. ) convulsions followed by autistic symptoms, so has live hepatitis B vaccine in 2 infants at age 2 years.
Cohen AD, Shoenfeld Y. Vaccine-induced Autoimmunity. Journal of Autoimmunity 9, 699-703, 1996.
Diverse autoimmune disorders have been reported following vaccinations. Vaccines have triggered autoimmune phenomena such as the appearance of DNA antibodies, localized disorders that are self-limiting ( e.g. reactive arthritis ) and systemic diseases, some of which are transient ( e.g. systemic lupus erythematosus (SLE) ). It seems that vaccines have a predilection to affect the nervous system: neuritis, demyelination, myasthenia gravis, and Guillain-Barre syndrome have been described.
Vaccine......................Autoimmune ( or possible autoimmune ) disorder
..................................................................
tetanus toxoid............optic neuritis, myelitis
influenza.....................vasculitis, reactive arthritis, Guillain-Barre syndrome
mumps, measles,........immune thrombocytopenic purpura
rubella
mumps.......................diabetes mellitus
rabies.........................neuritis, Guillain-Barre syndrome
hepatitis B.................erythema nodosum, immune thrombocytopenia,
...................................myasthenia gravis, uvetis, Reiter's syndrome,
...................................arthritis, systemic lupus erythematosus,
...................................central nervous system demyelination, DNA
...................................antibodies, Evan's syndrome
hepatitis A..................immune thrombocytopenia
oral polio vaccine .....Guillain-Barre syndrome
swine flu.....................multiple sclerosis
Suggested reading:
Vaccination: 100 years of orthodox research shows that vaccines represent a medical assault on the immune system
A Shot in the Dark
by Harris L. Coulter and Barbara Loe Fisher
SEE ALSO>>>Center for Complex Infectious Diseases
SEE ALSO OUR TREATMENTS PAGES>>> Treatments
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GALLUP_R
Subj: CDC meeting with NAAR
meeting with the Center for Disease Control (CDC) .
I understand that there will be a meeting with the Center for Disease Control (CDC) in Atlanta, GA. by the National Alliance for Autism Research (NAAR) , Eric and Karen London, on November 6-7th. I hope the subject about vaccine safety and adverse reactions to vaccines regarding autism will be brought up.
The following are articles and research involved concerning autism and adverse reactions to vaccines:
1. Dawbarns Fact Sheet on the MMR Vaccines and MR Vaccines - UK
2. JABS Newsletter No. 7 Spring '97 - UK
3. Letter by Trina Schmits dated 12/6/96 concerning her son, Tim
4. The Goldenberg Family article by Caremark
5. Journal of Autism and Developmental Disorders, Vol. 26, No. 4, 1996. S. Gupta, S. Aggarwal, & C. Heads. Brief Report: Dysregulated Immune System in Children with Autism: Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics.
6. Biotherapy 9: 143-147, 1996. H.H. Fudenberg. Dialysable Lymphocyte Extract (DLyE) in Infantile Onset Autism: A Pilot Study.
7. Journal Of Autoimmunity 9, 699-703, 1996. A.D. Cohen and Y. Shoenfeld. Vaccine - induced Autoimmunity.
8. IVIG studies by Sudhir Gupta, MD Univ. of Calif.,Irvine and James Oleske, MD UMDNJ,Newark - Elevated rubeola titers in autism due to MMR vaccination.
9. Vijendra K. Singh, Ph.D. Univ. of Michigan,Ann Arbor - 100 articles on autoimmunity and autism. Recent work regarding MMR and autism connection. Has been in the autism fiel for 10-15 years and Drs. Gupta and Fudenberg quote his work. Dr. Oleske has been working with Dr. Singh in conjuction with testing in regard to IVIG.
In the Vaccine-induced Autoimmunity article, autism is not mentioned but it says the following:
" Vaccines have triggered autoimmune phenomena such as the appearance of DNA antibodies, localized disorders that are self - limiting (e.g. reactive arthritis and systemic diseases, some of which are transient (e.g. systemic lupus erythematosus (SLE) ). It seems that vaccines have a predilection to affect the nervous system; neuritis, demyelination, myasthenia gravis and Guillain-Barre syndrome have been described."
One doctor at the National Vaccine Information Center conference said that the medical schools are not teaching that the immune system and nervous system are interconnected.
Parents and people concerned about autism and what adverse reactions to vaccines have done, please let NAAR know about your concern by contacting Eric and Karen London of NAAR at the following:
Email: naarlondon@delphi.com
Tel# : (908) 359-9957
Ray Gallup One of many parents whose child's autism was caused by an adverse reaction to a vaccine
YOUR RESPONSE.
- Adverse reactions became a big problem in Japan in 1975 and there was motivation to change. -
- There was a safer vaccine since 1981 in Japan using the new acellular vaccine instead of the whole-cell vaccine used in the U.S. -
- No public recognition in the U.S. of the extent of vaccine injuries because government health officials and members of the medical establishment have been denying there is a serious problem for more than 4 decades and American parents believed them. -
pg. 208 "A Shot in the Dark" by Harris Coulter
Personal note: It appears "Silence is Golden" in the U.S. SFTAH NOTE: IT IS THE SAME ALSO IN THE UK.
IF ANYONE HAS INFORMATION OR A RESPONSE REGARDING ANY OF THE BREAKING NEWS STORIES, OR INDEED A BREAKING STORY, PLEASE SEND IT TO US, TO BE INCLUDED ON THIS PAGE.
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Gene linked to autism.
"© Daily Mail Group, London 1997"
Scientists give new hope for autistics
Scientists have found the first gene to be linked to autism. The discovery could lead to treatments for the currently incurable disorder, which affects one child in 1,000 in britain.
Sufferers usually have difficulty forming relationships. They are often slow to develop speech and prone to repetitive behaviour. Most require special care throughout their life.
Now American researchers who studied 86 families have discovered that autistic children were much more likely to have a mutation of a gene linked to the body's chemical messenger serotonin-which they have in high levels.END....
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UPDATE 14.05.97.
Evidence Of Linkage Between The Serotonin Transporter And Autistic Disorder
Previous research has indicated that genetic factors contribute to an individual's likelihood of developing autism.
However, the genetics of autism are very complex. It is probable that more than one gene plays a causal role in this disorder. Therefore, it has been difficult to discern which of the many genes might be important.
The well-established finding that a significant number of people with autism have elevated levels of blood serotonin and the successful use of medications (potent serotonin transporter inhibitors, PSTIs) that partially treat the rituals in autism led to the possibility that serotonin may play a role in autism.
The PSTIs directly block a protein, the serotonin transporter, in some nerve cells in the brain. Therefore, the authors studied 86 people with autism and their parents to examine whether the gene for the serotonin transporter may contribute to the risk for autism. In this process, they have found evidence that there is a significant relationship between autism and this gene.
This is not only the first gene to be linked to autism but it is also consistent with long known information suggesting that abnormalities in serotonin functioning may contribute to autism.
If replicated by other researchers, this information may eventually contribute to the development of improved diagnosis and medical treatment of autism.
For further information, please contact the corresponding author, Dr. Edwin H. Cook, Jr., Director, Laboratory of Developmental Neuroscience, University of Chicago; Tel: +1 773 702-9692; Fax: +1 773 702-9929; e-mail: ed@yoda.bsd.uchicago.edu
EH Cook Jr., R Courchesne, C Lord, NJ Cox, S Yan, A Lincoln, R Haas, E Courchesne, BL Leventhal Departments of Psychiatry and Medicine, University of Chicago; Children's Hospital Research Center, La Jolla, CA, and University of California, San Diego, School of Medicine, USA
These articles will be published in the May issue of Molecular Psychiatry, an independent peer-reviewed journal published by Stockton Press/Macmillan Press.
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Gene--Original Research Article.
Evidence of linkage between the serotonin transporter and autistic disorder.
Reprinted by kind permission © Molecular Psychiatry (1997) Stockton Press. All rights reserved
E H Cook Jr1, R Courchesne2, C Lord2, N J Cox3, S Yan1, A Lincoln2, R Haas2, E Courchesne2,4 and B L Leventhal(1)
Laboratory of Developmental Neuroscience, Departments of Psychiatry and Pediatrics, MC 3077, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, 2 Autism and Brain Development Research Laboratory, Children's Hospital Research Centre, 8110 La Jolla Shores Drive, La Jolla, CA 92037; 3 Department of Medicine, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637; 4Neuroscience Department, School of Medicine, University of California at San Diego, La Jolla CA 92093, USA
The serotonin transporter gene (HTT) is a primary candidate in autistic disorder based on efficacy of potent serotonin transporter inhibitors in reducing rituals and routines. We initiated a candidate gene study of HTT in trios consisting of probands with autistic disorder and both parents. Preliminary transmission/disequilibrium test (TDT) analysis with 86 families revealed no evidence for linkage or linkage disequilibrium between autistic disorder and a polymorphism in the second intron of HTT. However, preferential transmission of a short variant of the HTT promoter was found in the same 86 trios (TDT x2 = 4.69, 1 d.f., P = 0.030). In further analses, we considered haplotypes of the HTT promoter variant and second intron locus as alleles in a multiallelic TDT. Results confirmed the significance of the effect of this region (TDT x2 = 11.85, 4 d.f., P = 0.018). This provides preliminary evidence of linkage and association between HTT and autistic disorder.
Keywords: linkage disequilibrium; linkage; autism, infantile; monoamines; transporter; serotonin; promoter; polymorphism
Introduction
Autistic disorder is characterized by qualitative impairments in reciprocal social interaction and communication, in addition to restricted and repetitive behaviours.1 The population prevalence of autistic disorder has been estimated between 5-10 per 10,000.(2) Estimates of the risk of sibling recurrence are much higher at 4.5%(3) to 8.9%,(4) resulting in a relative sibling recurrence risk of 45-178. Twin studies have demonstrated increased concordance in monozygotic twins relative to dizygotic twins,(5) The large decrease in risk to dizygotic twins relative to monozygotic twins6 and a latent class analysis7 are consistent with several loci contributing to susceptibility to autistic disorder.
Serotonin (5-HT) has been studied in autistic disorder since the finding in 1961 of increased whole blood 5-HT in the blood of children with autistic disorder.(8) A series of studies has replicated and extended this finding.(9) Whole blood 5-HT has been demonstrated to be positively correlated with serotonin uptake Vmax in both vervet monkeys(10) and humans.(11) In addition, potent serotonin transporter inhibitors have been demonstrated to be partially efficacious in the treatment of restricted and repetitive behaviours in autistic disorder associated with anxiety and/or aggression.(12..13) This led us to consider the serotonin transporter as a primary candidate gene in autistic disorder.
Two polymorphisms have been reported for the serotonin transporter gene, a variable number tandem repeat (VNTR) in the second intron(14) and a deletion/insertion polymorphism in the promoter which regulates expression of the 5-HT transporter in transfection assays and lymphoblastoid cell lines.(15.16) We examined possible linkage and linkage disequilibrium between autistic disorder and the serotonin transporter using the transmission/disequilibrium test (TDT).(17.18)
Materials and methods
Subjects
Consecutive subjects seen at the Autism and Brain Research Laboratory, Children's Hospital Research Center, La Jolla, CA between July 1990 and March 1993 and at the University of Chicago Developmental Disorders Clinic between June 1994 and October 1996 were considered for inclusion in the study. Inclusion criteria included a diagnosis of autistic disorder based on Autism Diagnostic Interview - Revised criteria,(19) clinical judgment of autistic disorder based on administration of the Autism Diagnostic Observation Schedule,(20) intelligence quotient greater than or equal to 35, and blood available for genotyping from the proband and both parents. Subjects were excluded if they had evidence of a known etioloty for a developmental disorder after neurological examination including examination of dysmorphology and neurocutaneous signs and appropriate laboratory testing. One subject was excluded because of an interstitial chromosome 15 q11-13 duplication. Subjects participated after providing written informed consent for themselves and their children, as appropriate. This study was approved by the institutional review boards of the University of Chicago and Children's Hospital, San Diego.
Eighty-six trios, consisting of a proband with autistic disorder and both parents were included in the study. Age of probands raged from 2.5 to 36 years (mean 8.5, standard deviation 7.6). Eighty subjects were male and six were female. Sixty-eight subjects were Caucasian, five were African-American, three were Hispanic-American and ten were Asian-American.
HTT 2nd intron VNTR analysis
DNA was extracted from whole blood using the Pure Gene DNA Isolation Kit (Gentra Systems, Minneapolis, MN, USA). Primers HTT2X (5'-TGGATTTCCTTCTCAGT GAQTTGG-3') and HTT2Y(5'-TCATGTTCCTAGTCTACGCCAGTG-3') amplified 345-bp (9 copy), 360-bp (10 copy), or 390-bp fragments containing the HTT 2nd intron variant. The primers were synthesized on an Applied Biosystems 380B DNA synthesizer at the Cancer Research Centre at the University of Chicago. PCR was performed in a 75-ml volume containing approximately 400 ng of genomic template, 0.5 mM of each primer, 200 mM of each dNTP, 2 units of Taq polymerase (AmpliTaq; Perkin-Elmer, Norwalk, CT, USA), 2mM MgCl2, 10 mM Tris-HCl, 50 mM KCl, and 0.001% gelatin. Samples were amplified in a geneAmp PCR System 9600 (Perkin-Elmer), beginning with an initial step of 2 min at 95oC, followed by 40 cycles of 15 s at 95°C, 30 s at 57°C, and 60 s at 72°C, followed by a 10-min final extension at 72°C. PCR product (75 ml) was concentrated to 10 ml by vacuum centrifugation (SpeedVac; Savant, Holbrook, NY, USA). Eight microlitres of concentrated PCR product were mixed with 3 ml of Sigma loading buffer. Ten microlitres of that mixture were separated at room temperature on 2% agarose (Perkin-Elmer) gels containing 0.5 mg ml-1 ethidium bromide in the TBE buffer (89 mM Tri8, 89 mM borate, 2 mM EDTA buffer, pH 8.0). Each gel contained two lanes of a 100-bp ladder (Gibco BRL, Gaithersburg, MD, USA). In the cases where fragments were not visible on agarose after 40 cycles of PCR, a fluorescently-labeled primer (Applied Biosystems) was used to amplify PCR products which were sized after injection on a ABI Prism 310 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA).
HTT promoter variant analysis
Two different primer sets were used to amplify the region containing the HTT promoter variant. The first set (stpr5, 5'-GGCGTTGCCGCTCTGAATTGC-3' and stpr3. 5'-GAGGGACTGAGCTGGACAACCCAC-3')15 amplified a 484/528-bp fragment. A second set (HTTp2A, 5'-TGAATGCCAGCACCTAACCC-3', and HTTp2B, 5'-TTCTGGTGCCACCTAGACGC-3') successfully amplified a 406/450-bp fragment from samples that failed to amplify with the first set. The primers were synthesized as above. PCR was performed in a 10-ml vol containing approximately 50ng of genomic template, 1mM of each primer, 200 mM each of dATP, dCTP, and dTTP, 100 mM each of dGTP and 7'-deaza-dGTP, 0.6 units of Taq polymerase (AmpliTaq; Perkin Elmer), 1.5 mM MgCl2, 5% DMSO, 10 mM Tris-HCl, 50mM KCl, and 0.001% gelatin. Samples were amplified using a Perkin Elmer GeneAmp PCR System 9600, through 40 cycles consisting of 30 s at 95øC, 30 s at 61øC, and 1 min at 71øC, followed by 10 min at 72øC. PCR products were separated on 2% agarose as above. In the cases where fragments were not visible on agarose after 40 cycles of PCR with 5-HTTp2A/B primer set, 50-55 cycles of PCR with AmpliTaq Gold, a heat-activated DNA polymerase (Perkin Elmer), and 2.5 mM MgCl2 were performed with an initial activation step of 12 min at 95øC.
Data analysis
The transmission/disequilibrium test was applied to each of the two HTT loci to test for linkage and linkage disequilibrium.17,18 In further analyses, we considered a haplotype of the HTT promoter variant and the HTT second intron VNTR loci. In constructing the haplotypes, we considered the probability of recombination to be negligible due to the close proximity of the markers (@ 15 kb).21
Results
All trios were completely genotyped at the two HTT polymorphisms. Preliminary TDT analysis with 86 trios of the planned 350 families revealed no evidence for linkage or linkage disequilibrium between autistic disorder and the VNTR in the second intron of HTT (TDT x2 = 4.25, 2 d.t.f., P = 0.110). However, preferential transmission of the short variant of the HTT promoter was found (TDT x2 = 4.69, 1 d.f., P = 0.018). Transmission data for alleles and haplotypes are presented in Table 1 from heterozygous parents only.
Discussion
Preliminary analysis of two serotonin transporter genetic markers revealed evidence of linkage between haplotypes of the two markers and autistic disorder. Individually, the short variant of the HTT promoter variant of the HTT promoter variant has recently been reported to be a quantitative trait locus for anxiety.16 Anxiety is often a prominent component of autistic disorder and anxiety disorders have been found to
Table 1. Transmission/disequilibrium test of HTT and autistic disorder.
_____________________________________________________________________
Serotonin transporter 2nd intron VNTR
9 copy .....................0....................5
10 copy..................32....................36
12 copy..................40....................31
TDT x2 = 4.25, 2 d.f.., P = 0.119
Serotonin transporter promoter variant
Short......................48.....................29
Long.......................29.....................48
TDT x2 = 4.69, 1 d.f., P = 0.030
Haplotypes of serotonin transporter 2nd intron VNTR and promoter variant
9 copy, long..............0.......................5
19 copy, short.........14.......................5
10 copy, long..........16.......................29
12 copy, short.........27.......................18
12 copy, long..........22........................22
TDT x2 = 11.85, 4 d.f., P = 0.018
_____________________________________________________________________
to be increased in relatives of probands with autistic disorder,( 22,23) One would not have predicted the short variant to be preferentially transmitted based on the limited data connecting hyperserotonemia and increased platelet serotonin transporter function, since the HTT promoter short variant was associated with reduced expression in transfected cell lines(15) and in lymphoblastoid cell lines. (16) Study of the relationship of the HTT promoter variants and central serotonin function will be required to fully define the relationships between HTT promoter genotype and HTT mRNA expression and serotonin transporter function.
Although most of the information in the haplotype analysis was provided by the promoter variant, the finding of the contribution by the HTT VNTR marker may indicate that the HTT VNTR marker has an effect on gene expression or that it is in linkage disequilibrium with another variation in the gene. Although studies of the relationship of the HTT promoter variants and function have shown differences in different tissues. It is possible that the HTT promoter variant is serving as a marker in linkage disequilibrium with a genomic variant which is contributing to susceptibility to autistic disorder. The haplotype analysis was performed to avoid the problem of multiple testing of the HTT variants. In this study, the more functionally relevant marker was in linkage with autistic disorder. Several lines of evidence suggest that the serotonin transporter is the most logical candidate gene based on existing evidence. However, many other candidates may be considered with only slightly weaker evidence in autistic disorder. Therefore, evidence for linkage in this study must be considered very preliminary. We are continuing to collect subjects in this study and beginning to collect a separate replication sample. More importantly, independent replication by other investigators would be necessary before linkage would be considered to have been demonstrated in autistic disorder.
A case-control association study has provided preliminary evidence of association between the HTT second intron24 and HTT promoter(25 )variants and bipolar mood disorder. Both our finding in autism the finding in bipolar mood disorder are preliminary and require replication. If both are replicated, it is possible that autistic disorder may share common risk at this locus, but that additional genetic and/or environmental factors may be required for the devellopment of either syndrome. In summary, the short variant at the serotonin transporter locus was found to be preferentially transmitted from parents to probands with autistic disorder. This provides preliminary evidence that the serotonin transporter may serve as a susceptibility locus in autistic disorder. If replicated, the finding may contribute to identification to other susceptibility loci which act additively or in a multiplicative manner. In addition, study of the relationship of genotypes at the serotonin transporter locus to response to potent serotonin transporter inhibitors may be feasible. Replication of this preliminary finding of linkage between the serotonin transporter locus and autistic disorder may be performed in other samples with a single affected child and both parents or in the several relatively large samples of affected sibling pairs.
Acknowledgements
Amy Jersild, Cory Shulman, Elizabeth Moreno, Matthew Leventhal, Jeremy Veenstra-Vander Weele, Pam DiLavore, Justine Levin, and Deborah Olkon provided expert technical assistance. This study was supported in part by NIMH R01 MH52223 (EHC), NINDS 5-R01-NS-19855 (EC), The Jean Young and Walden W Shaw Foundation (BLL), Harris Foundation (BLL), the Brain Research Foundation (EHC), and NIMH K05MH01196(CL)
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Gene:News and Views .
Reprinted by kind permission © Molecular Psychiatry (1997) Stockton Press. All rights reserved
Catch me if you can: are catechol- and indoleamine genes pleiotropic QTLs for common mental disorders? A number of recent independent studies have reported association between genes of the catechol- indoleamine systems and various complex human behavioural traits or disorders. While these findings must be treated with caution until replicated, they may represent some of the first successes of the candidate-gene allelic-association strategy in psychiatry. It is tempting to speculate that these gene families contain quantitative trait loci with pleiotropic effects, which will provide the key to the understanding of the interaction between genes and environment in behavioural disorders.
There is abundant evidence from human and animal studies that the central monamine (dopamine, noradrenaline and serotonin) systems are involved in arousal, motivation, reward and punishment; processes which may be maladjusted in common mental disorders such as depression, anxiety, phobias and substance misuse. Some drugs which alter the functioning of monoamine systems are effective in the treatment of these disorders while others are capable of inducing affective symptoms or drug dependency. Genetic polymorphism in these systems may therefore be responsible for part of the variability between individuals in the propensity to develop common mental disorders related to mood and reward.
Several recent studies have lent empirical support to this proposition. In this issue, three independent studies report associations between common mental disorders and allelic variants at catecholamine system genes; autism was connected with serotonin transporter,1 opioid dependence with Dopamine D4 receptor,2 and schizoid/avoidant personality with dopamine D2 receptor. 3 These studies follow closely on the heels of reports of associations between the serotonin transporter and depression,4,5 anxiety,6 bipolar affective disorder7 and Alzheimer's disease,8 between the dopamine D4 receptor and Tourette's syndrome9 and attention seeking behaviour,10,11 and a series of reports connecting the D2 receptor to reward-related behaviour such as alcoholism, drug misuse and gambling (reviewed in Ref. 3). While these findings should be interpreted with caution, the fact that it is almost always the same allele of the given polymorphism which appears to be associated with the disease or trait is encouraging.
Testing Candidate genes: allelic associations vs linkage The candidate-gene allelic-association strategy used by these studies represents with latest methodological shift in psychiatric genetics. Whole genome linkage scans using lod-score analysis of multiply affected families have recently identified a number of 'hotspots' for the major psychoses where the evidence for linkage is largely consistent but not compelling. These results have brought increasing recognition of the complexity of the inheritance of these disorders, and a shift of paradigm to non-parametric linkage analysis using affected sib-pairs.
The power of linkage analysis, whether parametric or non-parametric, is critically dependent on the magnitude of the effect of the 'mutant' allele. For an allele occurring in 10% of the population that doubles the risk of disease, more than 5000 affected sib-pairs are necessary to detect linkage at lod>3. The same effect could be detected in an association study of around 700 family trios (unrelated affected subjects and both their parents), even if the stringent criterion of P<0.0000005 is used to allow for multiple testing.12 This discrepancy in power is probably responsible for some of the negative linkage results in regions where allelic associations were subsequently demonstrated. Association analysis is therefore the method of choice for testing candidate loci.
While psychiatric genetic research was focused on schizophrenia and bipolar affective disorder, association analysis received relatively little attention because of the apparent lack of strong candidate loci for these disorders. The brain abnomalities consistently observed in schizophrenia suggest that the disorder is due in part to aberrant neurodevelopment, rather than merely neurochemical imbalance. In contrast, common disorders can be regarded as the maladaptive extremes of the normal variations in mood and personality; they are more likely to result from the functional imbalance of the neurochemical systems involved in the regulation of arousal, reward and punishment. They may be evolutionary advantages for a population to maintain a degree of variability in terms of emotional responses and personality traits. Such continuous characteristics are likely to be determined jointly by genetic variants at quantitative trait loci (QTLs) and environmental factors. Monoamine genes can be regarded as prime candidates for the QTLs influencing normal personality dimensions as well as for common disorders such as depression, anxiety, and addictions.
The gene-centred approach Another novel development is the shift of candidate gene studies away from the disease-centred to the gene-centred approach. The relative ease of collection of case-controls or family trios means that samples from many different diseases can be collected in a shorter time, allowing the analysis of the single gene for a variety of phenotypes. This approach can be further enhanced by attempting to break down a disease phenotype into related quantitative traits which may have a more direct relationship with underlying genetic defects.13 Collections of subjects measured for these traits provide a sensitive assay for a more subtle role of a given candidate gene as a behavioural QTL.
Are catecholamine and indoleamine genes pleiotropic QTLs for human mental disorders? A single QTL may pleiotropically influence distinct behavioural traits related to emotionality, as demonstrated by animal studies.14 Are candidate gene studies providing the first evidence for pleiotropic behavioural QTLs in humans? Caution is warranted, since some of these findings may turn out to be false positive associations. Aside from this, can these few genes play a substantial role in such apparently diverse diseases and behaviours? Twin studies have shown a high degree of genetic correlation between depression and anxiety, which is consistent with the hypothesis that inherited variation in the serotonin transporter may lead to pleiotropic effects on susceptibility to a range of disorders with an affective/anxiety component. Reward mechanisms in the brain may connect genetic variation in dopamine receptors with drug abuse and novelty seeking. It is thus tempting to speculate that genes in the serotonin and dopamine system are QTLs for human behaviours and their associated disorders.
If these speculations are correct, then association rather than linkage is more likely to provide the path that will eventually lead to an understanding of the genetic basis of common mental disorders. Viewed in this light, the reports in this issue and those in the recent literature, of allelic associations between several monoaminergic genes and common mental disorders are encouraging signs.
Replication
Failure to replicate allelic association findings is likely to be a continuing problem. Association between the e4 allele of ApoE and Alzheimer's disease was widely and almost universally replicated, an indication of the strength of the effect of this gene on susceptibility. For genes with smaller relative risks, which may vary between populations, replication is likely to be more difficult to achieve. In this issue, Ebstein et al 15 have not replicated the association reported by Lesch et al 6 between anxiety and the serotonin transporter. As Ebstein et al point out, this is not unexpected with repeated investigations designed to confirm initial findings across diverse cultural and ethnic categories. Meta-analysis can be used to evaluate the results of repeated investigations but will need to address the problems of ethnic and cultural variation in trait-gene associations. They are also subject to the effect of publication bias which may favour positive findings.
Can animal models help? Murine models of anxiety and substance abuse-related traits are perhaps the best in this regard, since they resemble human behaviours. However the loci detected for emotionality14 and opiate preference16 in murine models do not appear (as yet) to overlap with those detected by candidate gene studies in humans. 2.6 Are animal models leading us down the wrong path or a different one?
What next for psychiatric genetics? The probable outcome of the candidate gene approach is the indentification of a number of functional variants, each having a characteristic profile of effects on a number of psychological and behavioural dimensions, and on the propensity to develop common mental disorders. After the average effect of each allelic variant is quantified, further studies will be required to uncover gene-gene and gene-environment interactions. This will eventually lead to a detailed causal model from genotype and environment to phenotype. It would of course be surprising if all QTLs for common mental disorders are related to the monoamine system, and it is worth examining other largely neglected candidate neurochemical systems such as GABA and glutamate, plus any other genes suggested by animal models. Finally, a return to systematic genome scans (this time for allelic association) will be necessary to pick up unexpected QTLs missed by linkage and candidate gene approaches. Theoretical considerations and empirical observations indicate that, for most human populations, significant allelic associations are very likely to be present between loci that are less than ½ cM apart. If this is the case, then a whole genome 'linkage disequilibrium scan' can be conducted using over 3000 evenly spaced markers. With molecular genetic technology progressing at its present pace, genotyping will soon become feasible.
D A Collier
Section of Molecular Genetics
P C Sham
Section of Genetic epidemiology
Department of Psychological Medicine
Institute of Psychiatry
De Crespigny Park, London SE5 8AF, UK
References
1 Cook EH, Courchesne R, Lord C, Cox N, Yan S, Lincoln A, Haas R, Courchesne E, Leventhal B, Evidence for linkage between the serotonin transporter and autism. Mol Psychiatry 1997; 2: 247-250
2 Kotler M, Cohen H, Segman R, Gritsenko I, Nemanov L, Lerer B, Kramer I, Zer-Zion. M, Kletz I, Ebstein R. Excess dopamine D4 receptor (DRD4) exon III seven-repeat allele in opioid-dependent subjects. Mol Psychiatry 1997; 2: 251-254
3 Blum K, Braverman ER, Wu S, Cull JG, Chen TJH, Gill J, Wood R, Eisenberg A, Sherman M, Davis KR, Matthews D, Fischer L, Schnautz N, Walsh W, Pontius AA, Zedar M, Kaats G, Comings DE. Association of polymorphisms of dopamine D2 (DRD2) and dopamine transporter (DAT1) genes with schizoid/avoidant behaviours (SAB). Mol Psychiatry 1997; 2: 239-246
4.
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