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AUTISM FIRST STEPS
AUTISM DAILY NEWSLETTER     
Friday December 21, 2001  

INDEX:
*  Labour parents close ranks on MMR
*  The Biological Basis of Aggression
*  Chickenpox Vaccine Fails at U.S. Day Care Center
*  A helping hand for parents of autistic children
*   Xenon Genetics Announces the Discovery of Two New Drug Targets For
     Metabolic and Neurological Diseases

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Labour parents close ranks on MMR

 

Ministers in charge of the government's vaccination policy are resisting pressure to say whether their children have been given the controversial MMR jab.
I, as a government minister, have ensured that they (parents) can make these choices with all the information available

Jacqui Smith, health minister

Prime Minister Tony Blair angered opposition backbenchers on Wednesday by refusing to tell MPs if his baby son Leo had received the combined measles, mumps and rubella injection, which has been linked with autism. Health Secretary Alan Milburn has also refused to say whether his two sons, aged four and ten, were given the vaccine. Health Ministers Jacqui Smith and John Hutton, who both have young children, have also declined to reveal whether they went against government advice by paying for three separate vaccinations. Of the four-strong government health team only Yvette Cooper has shown her hand, by revealing that her two-year-old daughter had received the MMR jab. 'Protecting privacy' Responding to criticism that parents had a right to know if ministers personally had confidence in the jab, Ms Smith, who has two young sons, told BBC Radio 4's Today programme she wanted to protect her children's privacy.

Jacqui Smith: protecting her children



"They are not elected to Parliament I am - so I will answer for myself and for government policy." She said she understood people's concerns but latest research showed there was no link between MMR and autism, in line with government advice on the issue. Some parents have expressed their concerns about the safety of the vaccine and demanded their children be able to receive each vaccine separately. Ms Smith denied she was taking a 'holier than thou attitude' on the issue. "I, as a government minister, have ensured that they (parents) can make these choices with all the information available. "I think that is a perfectly reasonable position to take both as a government minister and a parent of children I want to protect." 'Need to know' The prime minister voiced his support for the triple vaccine, after pressure from Conservative MP Julie Kirkbride.
I'm not going to enter into any public discussion on the health of my children

Tony Blair

Ms Kirkbride, who was heckled loudly by Labour MPs, said she understood why Mr Blair wanted to keep details of his children's healthcare private. But with the government mounting a campaign for children to receive the MMR vaccine, there was a legitimate public interest in the issue

.

Kirkbride has herself given birth recently

"The public want to know whether the prime minister practices what he preaches," continued the MP. The prime minister told the Commons: "I'm not going to enter into any public discussion on the health of my children." 'Disappointed' Mr Blair stressed that the government's recommendation that children receive the MMR vaccine was supported by the World Health Organisation, the British Medical Association and other health bodies. He continued: "We fully support the campaign that is being mounted at the present time." Later, outside the chamber, Ms Kirkbride said: "I was disappointed that the prime minister did not use the opportunity to reinforce public confidence in the MMR vaccine. "I can only assume that he has something to hide, which is to say that little Leo has not had his jab." The Blairs have come under pressure from some newspapers in recent days to reveal whether Leo did have the disputed jab. The latest Medical Research Council findings have concluded that fears that autism was linked to the MMR vaccine were misplaced. 'Nobody's business' But their stance was backed by Liberal Democrat health spokesman, Dr Evan Harris. "Mr Blair, Mr Milburn and their colleagues are quite right to protect the confidentiality of their children's medical history. "It is nobody's business whether the child of a politician, or anyone else, has had the jab or had a contra-indication to the vaccination. "Anti-MMR MPs like Julie Kirkbride should argue their case on the science and when science does not support their position they should not bring their own or anyone else's children into the argument."


http://news.bbc.co.uk/hi/english/uk_politics/newsid_1720000/1720957.stm
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The Biological Basis of Aggression

by Joanna Schaffhausen
One need only pick up the daily newspaper to see how serious a problem violence is in today's society. Although the incidence of violent behavior in the US has fallen significantly in the past few years, there is still about an 80% chance that a person will be the victim of a violent crime during his or her lifetime. Even more troubling is the trend of increasing violence among the very young. After each school shooting, there is a media blitz of experts searching to explain how and why troubled teens sometimes turn to violence. Much of what they say is the result of research on the psychobiology of aggression, a field that has recently experienced many breakthroughs in identifying correlates of violent behavior. Some researchers claim that we are coming closer to predicting from a brain scan or a blood test whether a person is at risk for committing an act of violence. Ethical complications aside, a closer look at the neurobiology of aggression shows why we are unlikely to find a conclusive test for potential violent behavior. While there are many biological factors associated with aggression, their predictive value remains still quite low.

Figure 1. The Human Hypothalamus

The hypothalamus and pituitary gland are important parts of the brains limbic system associated with emotional response and arousal. These structures, along with the septum and amygdala, may play a role in mediating aggression.

The first hurdle in researching aggression is how to define it. It is an easier task with animals, who tend to display stereotyped patterns of violence such as killing to gain food or territory. With humans and non-human primates, classifying aggression becomes more difficult because there is complication of intent. Punishment, for example, represents an especially gray area. Should spanking be considered an aggressive act? What about capital punishment? Indeed, almost all acts we consider aggressive have been socially sanctioned by some cultures over the years. To simplify matters, many psychologists and ethologists find it useful to classify aggressive behavior into one of three main categories: (1) predatory aggression, which refers to stalking and killing of other species, (2) social aggression, which is unprovoked aggression that is directed an members of the same species for purposes of establishing dominance, and (3) defensive aggression, which refers to attacks delivered when an animal is cornered by a threatening aggressor. There is evidence from animal studies that suggests the different types of aggression are controlled by different subsets of brain structures within the limbic system, including the amygdala, the septum, and the hypothalamus (figure 1). For example, in the rat, lesions of the lateral septum decrease social aggression but increase predatory aggression, suggesting that neural substrates for offensive and defense aggression are intertwined but separate.  Next Page...

Page 2:Is it the Genes?

Hormones and Serotonin
Page 3:Reducing Violent Behavior

References

The Biological Basis of Aggression - Page 2

Is it in the Genes?One of the earliest attempts to link genetics and violent behavior occurred during the 1960s, when researchers thought they had discovered a propensity for violence in men born with an extra Y chromosome. Although the studies attracted a lot of attention at the time, further examination of XYY males revealed that they did not display any particularly violent tendencies. Furthermore, XYY males are extremely rare, and thus the syndrome could not possibly explain the frequency and prevalence of violent behavior around the globe. Scientists agree that there is probably a genetic component to aggression because violent behavior tends to run in families. However, with a complex behavior like aggression, it is especially difficult to separate genetic and environmental contributions. Most likely it is possible to inherit a predisposition to violence, but psychologists also stress that modeling aggressive behavior in the home is the surest method for propagating violence. "Sniper Charles Whitman, who killed several people from the University Tower at Texas, left a note behind that begged people to examine his brain for possible dysfunction. His autopsy revealed he had a tumor pressing into his amygdala."
A large body of research implicates the amygdala as a key brain structure for mediating violence. One of the first indications that the amygdala might be important for fear and aggression came from Kluver and Bucy's 1939 descriptions of monkeys who had their temporal lobes removed. They noted that the animals were remarkably tame and showed little fear. Later research indicated that docile behavior associated with Kluver-Bucy syndrome is likely mediated by the amygdala, as selective removal of that structure produced similar effects on fear and aggression. It is also possible to increase aggression through modulation of the amygdala. In animals, electrical stimulation of the amgydala augments all types of aggressive behavior, and there is evidence for a similar reaction in humans. Sniper Charles Whitman, who killed several people from the University Tower at Texas, left a note behind that begged people to examine his brain for possible dysfunction. His autopsy revealed he had a tumor pressing into his amygdala.
Hormones and Serotonin Testosterone is another attractive candidate for mediating aggression because males in of all ages, races and cultures are more physically aggressive than their female counterparts. In animals, testosterone is linked to social aggression. Reducing testosterone in the alpha male by castrating him eliminates his dominant social status, and restoring testosterone through injection causes him to regain his social status. However, administering testosterone to males with less social status does not usually allow them to take over the alpha male position, indicating that there is not a direct relationship between testosterone and position in the dominance hierarchy. There is some evidence in humans that high testosterone males are more likely to be socially aggressive, but no evidence that they are necessarily more violent. Often they are successful in professions that thrive on competition, such as successful leading of a company, running for president, or pursuing a sports career. Also, a few psychologists have suggested that females are not necessarily less aggressive than males; rather, they display a different kind of aggression. Females are more likely to show non-violent types of aggression such as ostracizing their peers or spreading false rumors with the intent to cause pain. Thus, while there does seem to be a connection between testosterone and physical aggression, a person's testosterone level will not necessarily be a good predictor of aggressive behavior. Several lines of converging evidence indicate that the neurotransmitter serotonin plays a key role in mediating aggressive and violent behavior. Mice with a selective knockout of the serotonin 1B receptor show an increase in aggression. Similarly, depleting serotonin levels in vervet monkeys increases their aggressive behavior, whereas augmenting serotonin levels reduces aggression and increases peaceable interactions like grooming. Serotonin has also been implicated in human aggression. For example, pharmacological interventions that augment serotonergic efficacy have been shown to reduce hostile sentiment and violent outbursts in aggressive psychiatric patients. Also, people with a history of impulsively violent behavior, such as arsonists, violent criminals, and people who die by violent methods of suicide show low levels of the serotonin in their cerebral spinal fluid. These findings represent an interesting correlation, but it is important to remember that the direction of effect is unclear. It may be that aggressive behavior induces low serotonin levels in the cerebral spinal fluid rather than vice versa. Measures of brain functioning such as the EEG have long suggested that violent criminals have impaired neurological processes, but the recent advancement of neuroimaging techniques has allowed researchers to examine violent offenders' brains in more detail. Adrian Raine and colleagues have conducted the largest and most thorough study to date, in which they used positron emission tomography (commonly called a PET scan) to compare brain activity in 41 convicted violent offenders to activity in 41 age matched control subjects. They found that the people convicted of murder had reduced activity in the prefrontal cortex and increased activity in subcortical regions such as the thalamus. This finding fits nicely with previous research showing that the damage to the prefrontal cortex impairs decision making and increasing impulsive behavior. Indeed, Raine's work is perhaps the best evidence yet that impaired brain functioning may underlie some types of violent aggression. However, it is important to remember that his subjects lie at the extreme end of a spectrum and are may not be typical of most aggressors. Also, there are plenty of examples of people with prefrontal cortex damage who do not commit violent acts, so PET scans cannot be used to ferret out potential murders.  Previous... | Next Page...

Page 2:Is it the Genes?

Hormones and Serotonin
Page 3:Reducing Violent Behavior

References

The Biological Basis of Aggression - Page 3

Reducing Violent BehaviorResearchers have been successful in identifying biological factors associated with aggression but have had less luck figuring out how these factors might contribute to pathological aggression and violence. At this point, there is no neurological marker to identify a person at risk for violent behavior, and it seems unlikely that a definitive test will ever exist. As the example of high testosterone males illustrates, aggression can often be channeled into healthy and beneficial behaviors. Thus it seems the best road to reducing dangerous kinds of aggression is learning more about the factors that shape aggressive behavior. Many people point to the media as a key instigator of violence, citing statistics about the thousands of dramatized murders American children watch on television each year, and there is some evidence to support this idea. However, television cannot possibly be the sole mediator of violent behavior. Toronto receives the same television programming as Chicago but the crime rate in the Canadian city is not even a tenth of the American one. The hard truth about pathological aggression is that it does tend to propagate through families, and once started, the cycle can be very difficult to break. Research on the neurobiology of aggression has already provided some valuable clues about possible targets for biological intervention, but there is no quick fix. The good news is that scientists in the fields of psychology, sociology and biology are increasingly aware of their mutual interest in this topic. Each brings a piece of the puzzle to the table, and their unique combination offers our best hope for understanding the complex behavior of pathological aggression.  Previous...

Page 2:Is it the Genes?

Hormones and Serotonin
Page 3:Reducing Violent Behavior

References


What did you think about this article? Send us your comments!
Joanna Schaffhausen earned a B.S. in psychology from Tufts University in 1996. She is currently a graduate student at Yale University, interested in the cellular mechanisms of learning and memory. References: Fuller, RW, "The influence of fluoexetine on aggressive behavior." Neuropsychopharmacology, 14: 77-81, 1996. Mann, JJ. "Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior,"Neuropsychopharmacology, 21 (2): 99S-105S, 1999. Raine, A., Buchsbaum, M., LaCasse, L., "Brain abnormalities in murders indicated by positron emission tomography," Biological Psychiatry, 42: 495-508, 1997. Virkkunen, M, Rawlings, R., Tokola, R., Poland, RE, Guidotti, A. Nemoff, D. Bisette, G., Kalogeras, K., Karonen, SL, Linnoila, M. "CSF Biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers," Arch of General Psychiatry, 51: 20-27, 1994.

http://www.brainconnection.com/topics/printindex.php3?main=fa/aggression
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Chickenpox Vaccine Fails at U.S. Day Care Center

By Anne HardingCHICAGO (Reuters Health) - A new report reveals that, at least among one group of youngsters, chickenpox vaccine was much less effective than past research has demonstrated.But the findings don't mean parents should stop vaccinating their children against chickenpox, one of the researchers, Jane Seward of the Centers for Disease Control and Prevention (news - web sites) (CDC) in Atlanta, Georgia, told Reuters Health.While some may consider chickenpox a mild disease, Seward noted that before the vaccine came into use in 1995, the viral illness killed 100 people and sent 10,000 to the hospital each year in the US. Complications of chickenpox can be serious, including bacterial infections in various parts of the body such as the lungs, as well as brain infections.``You can't predict who is going to have that bad outcome,'' Seward said.And, she noted, the number of severe cases of chickenpox has fallen by 85% since the introduction of the vaccine.Seward and her colleagues reported Tuesday on their investigation of a recent outbreak of chickenpox at a New Hampshire day care center. They presented their findings here at the Interscience Conference on Antimicrobial Agents and Chemotherapy.Past studies have shown the effectiveness of the vaccine against varicella, the virus that causes chickenpox, ranges from 71% to 91%. The current study found, however, that it was only about 40% effective.This is the first research that has shown ``anything significantly below'' the vaccine effectiveness of earlier reports, co-investigator B. R. Lee of the CDC told Reuters Health.The outbreak in 23 children also began with a child who had been vaccinated, contradicting the belief that such ''breakthrough'' cases are not contagious, Seward noted. The child, a 4-year-old, was confirmed not to have caught chickenpox from the vaccine, but probably contracted it from a sibling with shingles--which is caused by the same virus.Seward and Lee said they cannot yet explain why the vaccine may have been ineffective in this group of youngsters. ``We'd like to really understand what factors came together to produce it,'' Seward added. ``We're not dismissing it.''

http://dailynews.yahoo.com/h/nm/20011219/hl/chickenpox_1.html
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A helping hand for parents of autistic children

BY HELEN RUMBELOW

WHEN Barry Hall took early retirement at 50 it was not with dreams of golf and cruises, but because he was forced to provide full-time care for his adult autistic daughter. He is not alone, found a new report by the National Autistic Society, which showed that half of adults with autism are looked after at home by their parents. The effects on families who take on a lifetime’s care are devastating, found the report, with “marriages torn apart, siblings neglected, social lives and holidays destroyed, careers sacrificed.” Parents who fought gruelling battles to obtain an education for their autistic child find the provisions for adults even worse, said the charity. The most common fear among nearly 500 families surveyed was what will happen to the child when their parents die. As the condition only began to be properly diagnosed in the last few decades, no one yet knows the enormous impact this problem could have on Britain. The National Autistic Society desperately needs money to help these families which are left to cope alone. For Mr Hall, the last four years of full-time care for his daughter Hannah, who will be 23 on New Year’s Eve, have pushed him to the limits of his endurance: “I had to give up work because it became impossible due to the alien environment in which we live as a family. I am the last line of defence between Hannah and the world.” They failed to find the specialist school Hannah needed when she was young, and they finally took her out of her special needs school seven years ago when they discovered she was being locked in the changing room to contain her behaviour. Since then Mr Hall and his wife, Shirley, have been Hannah’s carers. They also look after their 12-year-old grandson at home because their elder son died ten years ago. An initial assessment by social services decided that the only equipment she needed was a “knife”, because she liked cooking. Mr Hall has battled to provide her with care assistants and talking devices: “It’s still so hard. Last weekend was pure hell, I was up around the clock for two nights, as she became difficult and started to tear the house down.” Linda Green, 46, from South London, knew she might have a similar battle in store when her autistic son John was reaching adulthood. So for a year she fought to find him a place in a specialist residential centre, where he moved this May. “When your child is at school it is bad enough fighting for the appropriate education, but that goes out the window when they grow up,” she said. “It was a big step, because lots of parents have nothing when they leave school, but that day when we had to unpack his stuff and leave him with strangers was really awful,” said Mrs Green. “He got into bed and said ‘see you in the morning’, but we knew that we wouldn’t be there, we were so upset coming home.” Six weeks after he moved into the home, Mrs Green received a call from a social worker saying that Jonathan could not continue there: “John was thrown out of a specialist adult placement after six weeks with nowhere to go, which is extremely worrying. Social services should be better prepared and parents need to be extremely vigilant.” They collected John and for the rest of the summer were his full-time carers. “We are virtually isolated. We don’t have anybody who comes to the house, we don’t go out or have a social life. When we do go out, we do what John wants,” she said. Now, the National Autistic Society has found a day-place for John, who is still recovering from the upheaval. “We are still in shock over what happened, and we still have to face the future. It sounds sombre, but we always worry about what will happen to him when we’re not here.”

http://www.thetimes.co.uk/article/0,,61-2001585098,00.html
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Xenon Genetics Announces the Discovery of Two New Drug Targets For Metabolic and Neurological Diseases

VANCOUVER, British Columbia, Dec. 19 /PRNewswire/ -- Xenon Genetics Inc.,The Clinical Genomics Company(TM), announced today that its scientists havediscovered two genes relating to metabolic and neurological diseases.  Each ofthese genes has been biologically validated as having an important function inhumans and each represents a novel genetic target which can be used toidentify small molecule compounds or other biologicals for therapeutic use.The genes were discovered using Xenon's comprehensive platform for geneticresearch which utilizes both clinical genomic and comparative genomicapproaches in humans and model organisms.Said Frank Holler, President & CEO of Xenon, "With these discoveries,Xenon's portfolio of validated genes associated with important biologicalpathways and human disease now stands at thirteen.  We have also identifiedmultiple genetic linkages, many of which we expect to yield additional geneticdiscoveries in the near future.  This growing pipeline of new genes and drugtargets provides an excellent springboard from which we can identify anddevelop new genetically derived drugs."The metabolic gene was initially identified in an animal model and has nowbeen shown to be a key regulator of iron metabolism in humans.  Furtherbiological evaluation has validated this gene as a drug target for theidentification of therapeutics for the treatment of iron disorders such ashemochromatosis and other iron overload syndromes.  Hemochromatosis is a lifethreatening disease that is estimated to affect over 1.5 million NorthAmericans.  It causes the accumulation of iron in body tissues, eventuallyresulting in the dysfunction of vital organs and leading to complications suchas diabetes, arthritis, cirrhosis of the liver and heart disease.  Aneffective drug could significantly reduce or eliminate the need for bloodwithdrawal or chelation therapy in patients afflicted with iron overloaddisorders.  Current available therapies for iron overload disorders such ashemochromatosis are generally poorly tolerated by patients who currentlyrequire their treatment in a hospital setting.  These modes of therapy are atsignificant cost to the health-care system.  Furthermore, new moleculardiagnostic techniques may also serve to identify individuals at increased riskfor hemochromatosis and in whom preventative therapies may be useful.Xenon's second gene discovery resulted from genetic analysis of rarefamilies with a form of epilepsy known as Idiopathic Generalized Epilepsy.Having validated this gene clinically in humans, Xenon has further shown thisto be a highly druggable target.  With an estimated 50 million people affectedworldwide, epilepsy represents a significant pharmaceutical marketopportunity.  Current anti-epileptic and anti-convulsant drugs constitute a US$4 billion market annually world-wide.  The United States constitutes 50% ofthis market.  However, most existing drugs have significant potential fortoxicity because of their lack of specificity against the drug target.Xenon's discovery may allow for the development of more specific drugtherapies for this common neurological condition.Said Michael Hayden, Chief Scientific Officer of Xenon, "These discoveriesfurther demonstrate Xenon's capacity to rapidly identify novel genes and drugtargets which play important roles in human disease pathways.  Our clinicalgenomics approach serves to accelerate drug discovery in that it yields genesand targets which are already biologically validated in humans.  This allowsus to move forward quickly into assay development and compound screeningwithout the necessity for an extensive period of target validation."About Xenon Genetics Inc.Xenon Genetics is a privately owned, genomics-based drug discovery companyengaged in identifying genes and other drug targets associated with humandisease and developing pharmaceutical therapies based on these genetically-derived targets.  The Company currently has 24 clinical collaborations inseven countries, providing access to DNA and clinical databases from32 distinct and informative populations.  The Company's drug discoveryprograms are targeted toward developing therapies for cardiovascular,neurological and metabolic diseases.  Xenon's lead drug discovery programs aredirected toward the development of therapies to raise HDL-cholesterol (or"good cholesterol"), lower triglycerides and correct the metabolic syndromeconstituting dyslipidemia, obesity and insulin resistance.  In its drugdiscovery programs, Xenon has identified multiple genetic linkages, diseaserelated genes and gene products that it is utilizing for the discovery ofnovel therapeutics.  Earlier this year, the Company completed a privateplacement financing for gross proceeds of US $47.6 million.  With its broadaccess to informative clinical populations and databases around the world,comprehensive approach to genetic analysis, multiple drug discovery programsand strong financial position, Xenon believes it is well positioned to becomean international leader in the application of clinical genomics for drugdiscovery.  For more information on Xenon Genetics, visit the company'swebsite at http://www.xenongenetics.com .This release contains forward-looking statements that are not based onhistorical fact.  These forward-looking statements involve risks,uncertainties and other factors that may cause the actual results, events ordevelopments to be materially different from those expressed or implied bysuch forward-looking statements.  Readers are cautioned not to place unduereliance on such forward-looking statementsFor further information please contact: Frank Holler, President & CEO ofXenon Genetics Inc., +1-604-484-3300

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/12-19-2001/0001636796&EDATE=
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ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.