Thursday, July 17, 2003                                                                            Vol. 7 No. 149

   IN TODAY'S SAR

     RESEARCH
   •  Autism Cases Continue To Increase At Record Pace
   •  New Insights Into Autism
   •  Could a Too-Male Brain Be One Cause of Autism?
   •  Six Abstracts on Head Size and Autism Research,
       (contains technical language.)
   •  New Frontiers in Research and Drug Discovery

    CARE
   •  Bobby Wants a Family to Call His Own

Autism Cases Continue To Increase At Record Pace

      [This report comes from autism advocate Rick Rollens.]

NOT include children under the age of 3 years old, nor does it include any persons with any other autism spectrum disorder such as PDD, NOS, or Asperger's Syndrome.)
      When examining the data more closely, DDS reports that the first quarter of 2003 (January 6, 2003 to April 4, 2003) produced the largest number of new cases for a first quarter reporting period in the 35-year history of the system, 832 new cases, accounting for an amazing 48% of all the new intakes for that period, which besides full syndrome autism, also includes mental retardation, cerebral palsy, epilepsy, and conditions similar to mental retardation like Down's and Fragile X.
      The second quarter report (April 4, 2003 to July 7, 2003) was the second largest second quarter report in the history of the system (846 new cases in the second quarter of 2002 vs. 831 new cases in the second quarter of 2003). Combined, for the first half of 2003, full syndrome autism cases are now representing 44% of all the new intakes, when historically that number has been as low as 3%.
      In the nine year period from July, 1994 to July, 2003, the number of cases of full syndrome autism has grown from 5,323 in 1994 to 22,040 in 2003...a 414% increase. Autism has for some time now been the faster growing disability in California's developmental services system. The most recent data from DDS confirms that, as the incidence of autism continues to grow with no end in sight.
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New Insights Into Autism
Study Focused on Head Size of Infants May Bring Hope of Earlier Diagnoses

      This news was reported in the Schafer Autism Report yesterday.  Since then, it has appeared in newspapers across the country.  This one comes from the Wall Street Journal By Sharon Begley.  Following the next article, also from the WSJ, are five research abstracts on head size and autism.
http://online.wsj.com/article_email/0,,SB105829013771139900-H9jeoNplal2nZynanqHb6uHm4,00.html

     To Margot and Jack Shaw, there was nothing worrisome in the very obvious difference between their twin boys: Even at 6 months, Andrew's head was dramatically larger than Daniel's. But because the boys, who turned 7 years old Tuesday, are fraternal and not identical twins, the Rye, N.Y., parents ascribed the difference to simple individual variation.
      Only in retrospect do they wonder how life would have been different if they had known that unusual head growth during infancy is an early warning sign. For although Daniel is a happy, normal kid today, Andrew is autistic.
      A new study offers a long-sought ray of hope for earlier diagnosis of children such as Andrew. The study in Wednesday's issue of the Journal of the American Medical Association finds that a small head circumference at birth followed by a sudden growth spurt of the head before the end of the first year is a reliable early warning sign of autism.
      The study, led by Eric Courchesne, a neurosciences professor at the University of California, San Diego, School of Medicine, supports one of the leading hypotheses for the underlying cause of autism. More importantly, it offers the possibility of early diagnosis and intervention.
      “Research supports the notion that the sooner you treat, the better the outcome,” says David L. Holmes, president of the Eden Institute Foundation in Princeton, N.J., an autism research and treatment center.
      National statistics on autism spectrum disorder are hard to come by, but the incidence has been rising mysteriously. The disorder, which ranges from severe to moderate cases, affects an estimated one in 160 children in the U.S., according to UCSD researchers. It is typically diagnosed between ages 2 and 4, based on a child's behavior -- delayed speech, difficulties with social interactions, poor attention, impaired exploration of the environment and inappropriate emotional responses.
      The difficulty of diagnosing autism, formally classified as a “pervasive developmental disorder” of the brain, has long been a bar to successful treatment. Although there is no cure, intensive interventions, speech and occupational therapy, communication instruction and social-skills training help. But timing is everything. By toddlerhood the brain is already becoming hard-wired with the circuits that underlie autism, notes Dr. Holmes, who wasn't involved in the UCSD paper.
      “It's much harder to treat these aberrant circuits than to prevent them from forming in the first place,” he says. “If we can treat autism before the synapses express themselves, we might be able to make these children indistinguishable from healthy kids by age 5. This is exciting stuff.”
      The Shaws didn't get their first inkling that something might be wrong with Andrew until he was 18 months old. It was then, says Mrs. Shaw, “that it seemed as if a neurological switch had been flipped. He stopped making eye contact, and wasn't walking.” Because of long waits to see neurologists and find an intervention that worked, she says, “we wasted almost two years.”
      The cause of the small brain size at birth is unknown. But the abnormally sped-up brain growth, says Dr. Courchesne, likely reflects excessive numbers of brain cells, failure of the brain to prune the hundreds of synapses that connect one neuron to another, or both. Normally, experiences sculpt the developing brain; unneeded or unused synapses are pruned away. Autistic children, in contrast, seem to suffer from the neurological equivalent of electrical overload: too many impulses, thoughts and sensations in their brain.
      “These abnormal connections make it very hard for autistic children to make sense of the world,” says Dr. Courchesne. “They withdraw.” The greater the brain overgrowth, report the UCSD scientists, the worse the brain abnormality and the more severe the autism.
      The San Diego team studied the records of 48 autistic pre-schoolers, ages 2 to 5. Using the U.S. Centers for Disease Control and Prevention growth charts for normal children and a standard head circumference benchmark, the scientists found that the head size at birth of the autistic children was, on average, in the 25th percentile (smaller than 75% of other newborns). But most of these children quickly began a period of such rapid brain growth that, by 6 to 14 months, they landed in the 84th percentile. By 4 or 5, their brain was the size of a typical 12-year old's.
      That brain overgrowth during infancy may be an early warning sign of autism “does seem plausible,” says Phillip L. Pearl, associate professor of pediatrics and neurology and an autism expert at Children's National Medical Center, Washington, D.C., who was not involved in the study. “It does seem that there is an abnormal acceleration of brain growth in children with autism.”
      Combined with earlier studies, the head-size finding pinpoints where, exactly, the brain is going off course. In autistic children, brain overgrowth in the first year is concentrated in the cerebral cortex, site of higher thought, intention and attention. In particular, myriad short-distance connections between neurons outnumber long-distance ones.
      Brain growth this early can't be triggered by the childhood immunizations that some activists accuse of causing autism. If the causes of the brain overgrowth can be traced to genes (in a recent paper, Dr. Pearl and colleagues noted that 20 genes are suspected of involvement in autism), in theory it might be possible to block their action through drugs or even gene therapy.
      More likely, though, prevention would come through therapy in the first year of life, before the developing brain becomes set in its autistic ways. Teaching the child basic skills like how to pay attention, interact with people and use words could rewire the developing brain and keep it on track.
      Head circumference isn't an infallible sign of autism. The UCSD team found that 6% of healthy children showed accelerated growth in head circumference from birth to between 6 and 14 months. (Excessive head growth can instead reflect a tumor, hematoma or another disorder.) Conversely, 41% of autistic children didn't have abnormal head growth.
      Still, says Dr. Courchesne, the measurement shows promise as an objective indication that something may be amiss. Although almost every hospital measures the head circumference of newborns, physicians don't always do so at each well-baby visit. “This could allow treatment to start one or three years earlier than is typically the case today,” says Dr. Courchesne. “If interventions start early, before abnormal neural circuits are irreversibly established, you should get a better outcome for the child.”
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Could a Too-Male Brain Be One Cause of Autism?

      [By Robert Mcgough for The Wall Street Journal.]
http://online.wsj.com/article_email/0,,SB10583036864206600-H9jeoNmlaZ2mpyoan2HbquIm4,00.html

     A respected cognitive scientist at Cambridge University has proposed a provocative theory: Autism can best be understood as an extreme version of the male brain.
      Dr. Simon Baron-Cohen defines the “extreme male brain” in quite a different way than being macho. He refers to two cognitive characteristics that differ measurably in most men and women.
      Women, he says, are slightly more empathetic than men on average -- that is, they are more likely to recognize, and respond to, the emotions of others. In tests, women are better at recognizing the emotions conveyed in photographs of eyes. In a skill related to social interaction, girls tend to develop language abilities and vocabulary faster than boys. Various studies show that women use both sides of their brains for language, while men use only one side, he says.
      Men, meanwhile, are on average slightly better at understanding systems that respond to inputs and outputs, he says. Examples include math, engineering and carpentry, fields that tend to be dominated by men. Systemizing, while a good way of interacting with things, is not a good way of handling the subtleties of social interaction, Dr. Baron-Cohen argues.
      Lack of empathy, late development of language skills and expertise in systems, taken to an extreme, describe many autistic people.
      There are other clues that autism may be linked to gender. Among those with classic autism, males outnumber females four to one, and among those with Asperger's Syndrome, which resembles a type of high-functioning autism, males outnumber females nine or 10 to one.
      If Dr. Baron-Cohen is right, his theory may lead to new options for detection of autism, and one day could even lead to prevention or treatment.
      Dr. Baron-Cohen “has got a handle on one thing that's been noticed for a long time and nobody's dared to deal with it,” says Uta Frith, a professor at the Institute of Cognitive Neuroscience at University College London. “This theory is ambitious, and it may not explain everything about autism,” she adds, but currently there is no theory explaining all of autism.
      Some researchers think it is an audacious leap to go from maleness to autism. Isabelle Rapin, a professor of neurology and pediatric neurology at New York's Albert Einstein College of Medicine, finds Dr. Baron-Cohen's theory “provocative” but adds that “it does not account for some of the many neurological features of the disorder, like the motor symptoms [such as repetitive movements and clumsiness], the sleep problems or the seizures.”
      Others worry that the term “extreme male brain” could be misinterpreted. Males are commonly associated with “qualities such as aggression,” says Helen Tager-Flusberg, professor of anatomy and neurobiology at Boston University School of Medicine. “What's dangerous is that's the inference people will make: Oh, these are extreme males.”

study he did of more than 1,000 Cambridge University students, science-oriented students, including those studying engineering, mathematics and computer science, had a higher rate of autism in their families than humanities students.
      Why? A freezer in the basement of a laboratory at Cambridge may hold a vital clue. Inside the freezer are test tubes with samples of amniotic fluid from 3,000 children born in England two to four years ago. That fluid shows how much testosterone the children were exposed to in the fetus.
      Already, Dr. Baron-Cohen and colleagues have checked some of those children at ages 12 months and 24 months. While autism isn't usually diagnosed so early, the researchers did find that the higher the levels of fetal testosterone, the less the children made eye contact with others. A hallmark of autism is a marked lack of eye contact. Moreover, the children with lower levels of fetal testosterone had larger vocabularies.
      Now the team is tracking down children who are diagnosed with autism, Asperger's Syndrome or related conditions, such as language delay and low social sensitivity, and then checking their amniotic fluid for testosterone. The results won't likely be known for another year.
      If evidence supports Dr. Baron-Cohen's theory, parents could one day face the type of ethical challenges familiar in other lines of genetic research: Should they screen for testosterone as an indicator of risk for autism? Should they seek any treatments that are developed to counteract it? Dr. Baron-Cohen cringes at talk of “treating” autistic people, saying that while some suffer because of their condition, others consider it an integral part of themselves they wouldn't want to change.
      He also says the world might be poorer without them. He cites evidence that some greats of science and mathematics, such as Isaac Newton, might have had autistic tendencies.
* * *

Six Abstracts on Head Size and Autism Research,
contains technical language.

Macrocephaly in Children And Adults With Autism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9031582&dopt=Abstract

1: J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):282-90.
Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, Folstein SE.
University of Utah, Salt Lake City 84108, USA.

      OBJECTIVE: To explore the frequency and onset of macrocephaly in autism and its relationship to clinical features.
      METHOD: Head circumferences at birth, during early childhood, and at the time of examination were studied in a community-based sample of autistic children and adults. The authors investigated whether head circumference at the time of examination was associated with clinical features.
      RESULTS: Fourteen percent of the autistic subjects had macrocephaly: 11% of males and 24% of females. In most, the macrocephaly was not present at birth; in some it became apparent in early and middle childhood as a result of increased rate of head growth. A small relationship was noted between head circumference percentile and less severe core features of autism. Neither macrocephaly nor head circumference percentile was associated with nonverbal IQ, verbal status, seizure disorder, neurological soft signs or minor physical anomalies in the autistic subjects.
      CONCLUSION: Macrocephaly is common in autism and usually is not present at birth. Rates of head growth may be abnormal in early and middle childhood in some (37%) children with autism. Macrocephaly does not define a homogeneous subgroup of autistic individuals according to clinical features.
      PMID: 9031582 [PubMed - indexed for MEDLINE]
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Brief Report: Cognitive Correlates Of Enlarged Head Circumference In
Children With Autism

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12757362&dopt=Abstract

1: J Autism Dev Disord. 2003 Apr;33(2):209-15.
Deutsch CK, Joseph RM.
Eunice Kennedy Shriver Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

      This study examined the frequency and cognitive correlates of enlarged head circumference in a sample of 63 children with autism between the ages of 4 and 14. Consistent with prior evidence, macrocephaly occurred at a significantly higher frequency than in a normal reference sample.
      Head circumference was not associated with language or executive functioning, nor was it related to verbal or nonverbal IQ. Head circumference was, however, correlated with discrepancies between verbal and nonverbal IQ scores, independent of absolute level of verbal ability.
      Children with discrepantly high nonverbal abilities had a mean standardized head circumference that was more than 1 SD greater than in the reference sample, and that was significantly greater than in autistic children with a relative verbal advantage or no discrepancy in cognitive abilities, for whom mean head circumference was within normal limits.
      This convergence of physical and cognitive features suggests a possible etiologically significant subtype of autism.
      PMID: 12757362 [PubMed - in process]
* * *

Head Circumference An Independent Clinical Finding Associated With Autism

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11186888&dopt=Abstract

1: Am J Med Genet. 2000 Dec 11;95(4):339-50.
Miles JH, Hadden LL, Takahashi TN, Hillman RE.

      Comment in: Am J Med Genet. 2001 Dec 15;104(4):342. 

Division of Medical Genetics, The Children's Hospital, University of Missouri-Columbia, 65212, USA. milesjh@missouri.edu 

      Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurable. As part of a study of genetic heterogeneity of autism, we scrutinized data from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) values of the autistic propositi (0.61+/-1.6) varied significantly from that of the normal population (0.0+/-1.0), (P<0.001).
      Comparison of the macrocephalic (OFCSD > 2.0, N = 32) with the normocephalic individuals (-2 SD < OFCSD < +2 SD, N = 95) showed no significant differences in sex ratio, morphological status, IQ, seizure prevalence, or recurrence risks. The macrocephalic individuals were slightly less apt than those with normocephaly to have a family history of Attention Deficit Hyperactivity Disorder (ADHD) (P<0.05). Each clinical subgroup of autism propositi, defined on the basis of phenotypic status, type of onset, seizure history, or IQ, had a higher than normal mean OFC indicating that macrocephaly is an independent clinical trait in autism.
      As in the non-autistic population, macrocephaly was highly familial with 45% of the macrocephalic and 37% of the normocephalic propositi having at least one macrocephalic parent. Microcephaly, however, was an independent significant variable that predicted the presence of other phenotypic or genetic traits and outcome.
      The microcephalic patients were more likely to have abnormal physical morphology, structural brain malformations, lower IQ, and seizures. Their sex ratio was closer to normal, and their relatives had a higher incidence of seizures.
      PMID: 11186888 [PubMed - indexed for MEDLINE] 
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Microcephaly and Macrocephaly In Autism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10382131&dopt=Abstract

1: J Autism Dev Disord. 1999 Apr;29(2):113-9.
Comment in:  J Autism Dev Disord. 2000 Aug;30(4):365. Fombonne E, Roge B, Claverie J, Courty S, Fremolle J.
Institute of Psychiatry, MRC Child Psychiatry Unit, London, United Kingdom.
 
     Data from a series of 126 autistic children ages 2-16 years and referred to an Autism Diagnosis Unit in South-West France were examined. Macrocephaly (head circumference > 97th centile) was observed in 16.7% of the sample, a significantly higher proportion than that expected.
      Macrocephaly was more frequent among older subjects but was otherwise not associated with gender, developmental level, the presence of epilepsy or of medical disorders, or severity of autistic symptomatology.
      Microcephaly (head circumference < 3rd centile) was also significantly raised and found in 15.1% of the sample. Microcephaly was significantly associated with the presence of medical disorders. Results support those from recent studies suggesting a raised rate of macrocephaly in autism which, pooling published data, can be estimated to be 20%.
      It is argued that the raised incidence of microcephaly among low-functioning autistic subjects with medical disorders might have contributed to delay the recognition of an increased head circumference among a minority of subjects with idiopathic autism.
      Publication Types: Clinical Trial
      PMID: 10382131 [PubMed - indexed for MEDLINE] 
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Is Megalencephaly Specific To Autism?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10466865&dopt=Abstract

1: J Intellect Disabil Res. 1999 Aug;43 ( Pt 4):279-82.
Ghaziuddin M, Zaccagnini J, Tsai L, Elardo S.
University of Michigan, Ann Arbor 48109-0390, USA. mghaziud@umich.edu 

      Several recent reports have described the presence of increased head circumference (megalencephaly) in patients with autism. Although some studies have described reports of megalencephaly in other disorders such as schizophrenia in adults, few such studies have been performed in children and adolescents. In the present study, the authors compared 20 subjects with autism/ pervasive developmental disorder (DSM-IV; all males; mean age = 10.9 years) with 20 controls with attention deficit hyperactivity disorder (DSM-IV; all males; mean age = 11.1 years).
      Four subjects and five controls had evidence of megalencephaly. In addition to their core symptoms, the autistic subjects with megalencephaly were hyperactive and impulsive. These findings suggest that megalencephaly may not be specific to autism, and when present, it may index the presence of additional symptoms such as hyperactivity and impulsivity.
      PMID: 10466865 [PubMed - indexed for MEDLINE]
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New Frontiers in Research and Drug Discovery

      The New York Academy of Sciences has published an Academy e briefing on their website. 
      This mini-symposium was organized by Peter Bell, CAN board member and Franchise Director for McNeil Specialty Pharmaceuticals and Doug Compton, member of CAN’s Scientific Review Council.
      The website address is: http://www.nyas.org/aeb/autism/index.html
      At the website you can view the full meeting report, slides, research agenda, speaker bios, references and resources.
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CARE

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