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zoom RSS 自閉症発症には胎内状態を含めた環境要因が遺伝子と同じくらいに重要

<<   作成日時 : 2011/07/06 20:10   >>

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 双生児についての新たな研究で、自閉症の発症には、子宮内状態を含めた環境要因が遺伝子と同じくらいに重要な因子となる可能性があるという。
 現在、先進国で人口の少なくとも1%に自閉症が発症する。
 この研究は、遺伝因子が原因に含まれることが確認された重要な研究だが、環境因子も実際重要であるという可能性に目を向けた。
 ほんの数十年前には、精神科医は母親の愛情不足により自閉症が引きおこされると思っていた。しかしその考え方は遺伝子因子による説明で棄却されてきたのだが、一方で、自閉症の発症率は遺伝子の進化よりずっと早く増加してきている。現在では、遺伝と環境の両因子を正確に考慮する必要がある。
 親の年齢、多胎妊娠、低出生体重、妊娠中の薬物や感染といった因子も考慮する必要がある。
双生児についての新たな研究では、192組の一卵性と二卵性の双生児を追跡した。双子の少なくとも1人が古典的な自閉症をもち、多くはもう一方も古典的な自閉症やAsperger症候群のようなより軽症の「自閉症スペクトラム」であった。
 自閉症・自閉症スペクトラムが、一卵性双生児の両方に男子で77%、女子で50%みられた。二卵性では男子で31%、女子で36%だった。数学的なモデリングによれば、遺伝因子の寄与は38%であり、以前の研究報告の90%に比較して低かった。驚いたことに、環境要因が58%寄与していた。双生児でない兄弟の発症率は低く、出生後よりも子宮内での環境要因が自閉症の発症に寄与している。
 もう一つの研究では、よく使用される抗うつ剤SSRIの出産前服用により自閉症発症のリスクが2倍に上昇するという。しかし、出産1年前の服用で2.1%、妊娠初期で2.3%とリスク絶対値は低い。

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Environment, not just genetics, at play in autism
http://www.reuters.com/article/2011/07/04/us-autism-environment-idUSTRE7634Y220110704

By Julie Steenhuysen

CHICAGO | Mon Jul 4, 2011 5:13pm EDT

(Reuters) - Environmental factors may play a greater role in autism than previously thought, tipping the scale away from a strict focus on genetics, two studies released on Monday suggest.

In one, a team at Stanford University compared cases of autism in identical and fraternal twins and found that fraternal twins -- who share only half of the same genes -- have unusually high rates of autism, suggesting that factors other than genetics may be triggering the disease.

In another, researchers at health insurer Kaiser Permanente found mothers of children with autism were twice as likely to have been prescribed a common antidepressant during the year before their pregnancy than mothers of healthy children.

And the risk was even greater -- a threefold increase -- when the drug was taken in the first trimester of pregnancy.

The findings, released in the Archives of General Psychiatry, suggest that something in the birth environment -- drugs, chemicals or infections -- may be triggering autism in children who are already genetically predisposed to develop the disease.

"It has been well-established that genetic factors contribute to risk for autism," Clara Lajonchere, a study co-author and vice president of clinical programs for Autism Speaks, said in a statement.

"We now have strong evidence that, on top of genetic heritability, a shared prenatal environment may have a greater than previously realized role in the development of autism."

Autism is a spectrum of disorders ranging from a profound inability to communicate and mental retardation to relatively mild symptoms such as with Asperger's syndrome.

It affects one in every 150 children born today in the United States, or about 1 percent of the population.

SHARED ENVIRONMENT

The Stanford study involved 54 pairs of identical twins, who share 100 percent of the same genes, and 138 pairs of fraternal twins, who share half of the same genes.

In each pair, at least one of the twins had been diagnosed with autism.

The researchers found the chances of both children having autism spectrum disorder was higher among identical twins than among fraternal twins. But fraternal twins were much more likely to develop autism than studies of children in families where a sibling has autism.

According to the study, environmental factors common to twins explain about 55 percent of the cases of autism, and while genetic factors still play a role, it is much lower than seen in other studies of twins and autism.

"Environmental factors play a bigger role than previously thought," said Dr. Joachim Hallmayer of Stanford University School of Medicine in California, who led the study.

Recent studies have suggested genetics played the biggest role in autism, but his findings suggest something different, he said in a telephone interview.

"We have to study both the genetics and the environment," Hallmayer said. "If we look only at one side, I don't think that will lead us to the right answer."

COULD IT BE ANTIDEPRESSANTS?

In a separate study in the same journal, a team led by Lisa Croen, director of the Autism Research Program at the Kaiser Permanente Division of Research in Oakland, California, looked to see whether antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, contributed to autism risk.

The team studied nearly 300 children with autism and 1,500 randomly selected children and then checked their mothers' medical records.

They found mothers of the children with autism were twice as likely to have taken an antidepressant in the year before delivery than children in the control group.

And the effect was strongest -- three times higher -- when the drugs were taken in the first trimester of pregnancy.

"Our results suggest a possible, albeit small, risk to the unborn child associated with in utero exposure to SSRIs," Croen said in a statement.

But she said this risk must be balanced with the risk to the mother of having untreated depression.

The team cautioned that the SSRI study was preliminary and said much more work was needed to understand the link between antidepressants and autism.

"There are real risks to not being treated for a serious illness like depression. You have to weigh the options," said Dr. Thomas Insel, director of the National Institute of Mental Health.

"A threefold increase in risk is not insignificant. It is worth taking that into account with other factors," Insel said in a telephone interview.

Insel, whose agency funded the twins study, said it is not yet clear what environmental factors may be triggering autism.

"It could be a range of things from infection to chemical exposures. We simply don't know."

What is becoming clear, he said, is that the exposure is likely occurring before childbirth.

"From all the studies that so far have concluded, that is where the evidence seems to be going," he said.

(Editing by Doina Chiacu)

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画像Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism

Joachim Hallmayer, MD; Sue Cleveland, BS; Andrea Torres, MA; Jennifer Phillips, PhD; Brianne Cohen, BA; Tiffany Torigoe, BA; Janet Miller, PhD; Angie Fedele, BA; Jack Collins, MBA; Karen Smith, BS; Linda Lotspeich, MD; Lisa A. Croen, PhD; Sally Ozonoff, PhD; Clara Lajonchere, PhD; Judith K. Grether, PhD; Neil Risch, PhD

Arch Gen Psychiatry. Published online July 4, 2011. doi:10.1001/archgenpsychiatry.2011.76

Context Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins.

Objective To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment.

Design, Setting, and Participants Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services.

Main Outcome Measures Structured diagnostic assessments (Autism Diagnostic Interview--Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD).

Results For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD).

Conclusion Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.

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Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders

Lisa A. Croen, PhD; Judith K. Grether, PhD; Cathleen K. Yoshida, MS; Roxana Odouli, MSPH; Victoria Hendrick, MD

Arch Gen Psychiatry. Published online July 4, 2011. doi:10.1001/archgenpsychiatry.2011.73

Context The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.

Objective To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.

Design Population-based case-control study. Medical records were used to ascertain case children and control children and to derive prospectively recorded information on mothers' use of antidepressant medications, mental health history of mothers, and demographic and medical covariates.

Setting The Kaiser Permanente Medical Care Program in Northern California.

Participants A total of 298 case children with ASD (and their mothers) and 1507 randomly selected control children (and their mothers) drawn from the membership of the Kaiser Permanente Medical Care Program in Northern California.

Main Outcome Measures ASDs.

Results Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]). No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.

Conclusion Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders. Further studies are needed to replicate and extend these findings.


Author Affiliations: Division of Research, Kaiser Permanente Northern California, Oakland (Dr Croen and Mss Yoshida and Odouli), Environmental Health Investigations Branch, California Department of Public Health, Richmond (Dr Grether), and Department of Psychiatry, Neuropsychiatric Institute and Hospital, University of California, Los Angeles (Dr Hendrick).


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自閉症発症には胎内状態を含めた環境要因が遺伝子と同じくらいに重要 医師の一分/BIGLOBEウェブリブログ
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