" ...if neurodevelopmental systems are so robust, then why do we ever get neurodevelopmental disease?" Two words: environmental damage

Maternal Antibodies to Gluten Linked to Schizophrenia Risk in Children http://www.sciencedaily.com/releases/2012/05/120510113519.htm "Lifestyle and genes are not the only factors that shape disease risk, and factors and exposures before, during and after birth can help pre-program much of our adult health," said investigator Robert Yolken, M.D., a neuro-virologist at Johns Hopkins Children's Center. Maternal infections and other inflammatory disorders during pregnancy have long been linked to greater risk for schizophrenia in the offspring but, the Swedish and U.S. investigators say, this is the first study that points to maternal food sensitivity as a possible culprit in the development of such disorders.

Fish Show Autism-Like Gene Expression in Water With Psychoactive Pharmaceuticals http://www.sciencedaily.com/releases/2012/06/120606193853.htm "Psychoactive medications in water affect the gene expression profiles of fathead minnows in a way that mimics the gene expression patterns associated with autism spectrum disorder in genetically susceptible humans, according to research published June 6 in the open access journal PLoS ONE"

Fever During Pregnancy More Than Doubles the Risk of Autism http://www.sciencedaily.com/releases/2012/05/120523161941.htm "Another recent study based on CHARGE data found that mothers who were obese or diabetic had a higher likelihood of having children with autism." "Since an inflammatory state in the body accompanies obesity and diabetes as well as fever," said Hertz-Picciotto, "the natural question is: Could inflammatory factors play a role in autism?" "Our study provides strong evidence that controlling fevers while pregnant may be effective in modifying the risk of having a child with autism or developmental delay,"

New Evidence Links Immune Irregularities to Autism, Mouse Study Suggests http://www.sciencedaily.com/releases/2012/07/120717141010.htm ...the researchers injected pregnant mothers with a viral mimic that triggered the same type of immune response a viral infection would. "In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson's lab and lead author of the PNAS paper.

My bad. I neglected to include the juicy part from the above story. The Autism symptoms that were triggered by the viral infection were successfully treated with a bone marrow transplant. "In the most revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like behavioral impairments."

Mark Houston I'm sure if you asked the studies authors they would tell you that the connection between obesity and Autism is in some way related to harmful inflammation or a secondary consequence of harmful inflammation. The next time you read that a disease is associated with obesity think associated with inflammation. The two are connected like pepperoni and cheese.

Research that looks for correlations between heredity and illness becomes less impressive by the day. However the recent discovery that hypoxia might underlie congenital birth defects is earth shaking. http://www.sciencedaily.com/releases/2012/04/120405131220.htm Nature and Nurture: World‐first Discovery Sheds New Light On Congenital Birth Defects --excerpt Dunwoodie's group then went on to test the genetic risk factor in a mouse model combined with an environmental insult in the form of hypoxia. Surprisingly, they found a marked increase in spinal abnormalities in the offspring, when the mothers were exposed to only 8 hours of low oxygen during an entire 21‐day pregnancy. "We found that the combination of the genetic risk as well as exposure to low oxygen, resulted in our subjects being up to 10 times more likely to develop congenital scoliosis, than those that only had the genetic risk factor," says Dunwoodie. "What this brief period of low oxygen essentially did was disrupt the pathway responsible for development of the spine, and we know that the same pathway is used in the development of limbs and many organs, including the heart, kidneys, brain and cranio‐facial region," adds Dunwoodie. Bob Graham, a professor and executive director of the cardiac research institute, says around 25 percent of patients with congenital scoliosis also have some form of congenital heart defect, indicating that a single environmental 'insult' such as hypoxia, can potentially affect the development of more than one organ in the body.

Uh oh, maternal obesity increases the risk of Autism by about 2/3rds. Obesity is associated with chronic inflammation and inflammation is associated with almost every disease process mankind has ever studied. http://www.sciencedaily.com/releases/2012/04/120409103942.htm Maternal Obesity, Diabetes Associated With Autism, Other Developmental Disorders "...mothers who were obese were 67 percent more likely to have a child with ASD than normal-weight mothers without diabetes or hypertension, and were more than twice as likely to have a child with another developmental disorder." "The authors note that obesity is a significant risk factor for diabetes and hypertension, and is characterized by increased insulin resistance and CHRONIC INFLAMMATION, as are diabetes and hypertension. In diabetic, and possibility pre-diabetic pregnancies, poorly regulated maternal glucose can result in prolonged fetal exposure to elevated maternal glucose levels, which raises fetal insulin production, resulting in chronic fetal exposure to high levels of insulin."

kjmtchl "We identified POTENTIALLY causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3." You wrote that these 4 mutations cause Autism and yet the study abstract says that they are "potentially causitive". Over the last 20 years the only common denominator I've seen in the field of genetics is oversold findings. While it's certainly possible that these 4 genes trigger Autism I wouldn't bet on it. If history is any guide future research will suggest that they are merely associated with an increased risk of disease or the original discovery was a false positive.

kjmtchl Maybe that didn't come out quite right. I didn't mean that you were overselling a particular finding. I mean that EVERYONE oversells these findings. If tomorrow scientists discover that a gene raises the risk of Disease X by 10% the headline the next day will be "Scientists Find Gene That Causes Disease X". It's easy to become cynical.

I question the assumption that many common diseases are caused by heredity in the first place. How Your Cat Is Making You Crazy http://www.theatlantic.com/magazine/archive/2012/03/how-your-cat-is-making-you-crazy/8873/ “I’d say 75 percent of cases of schizophrenia are associated with infectious agents, and Toxo would be involved in a significant subset of those.”

kjmtchl, from the article, "Many schizophrenia patients show shrinkage in parts of their cerebral cortex, and Flegr thinks the protozoan may be to blame for that. He hands me a recently published paper on the topic that he co-authored with colleagues at Charles University, including a psychiatrist named Jiri Horacek. Twelve of 44 schizophrenia patients who underwent MRI scans, the team found, had reduced gray matter in the brain—and the decrease occurred almost exclusively in those who tested positive for T. gondii. After reading the abstract, I must look stunned, because Flegr smiles and says, “Jiri had the same response. I don’t think he believed it could be true.” When I later speak with Horacek, he admits to having been skeptical about Flegr’s theory at the outset. When they merged the MRI results with the infection data, however, he went from being a doubter to being a believer. “I was amazed at how pronounced the effect was,” he says. “To me that suggests the parasite may trigger schizophrenia in genetically susceptible people.”

kjmtchl, here is another Toxo/Schiz story from early 2008. Toxoplasma Infection Increases Risk Of Schizophrenia, Study Suggests http://www.sciencedaily.com/releases/2008/01/080116123517.htm "Researchers found that of the 180 study subjects diagnosed with schizophrenia, 7 percent had been infected with toxoplasma prior to their diagnosis, compared to 5 percent among the 532 healthy recruits. Thus, people exposed to toxoplasma had a 24 percent higher risk of developing schizophrenia." “Our findings reveal the strongest association we’ve seen yet between infection with this very common parasite and the subsequent development of schizophrenia,” says Robert Yolken, M. D., a neurovirologist at Hopkins Children’s who was among those conducting the analysis. Previous studies have reported on the link between schizophrenia and the presence of toxoplasma antibodies, which are evidence of past infection, but this is the first study to show that infection with the parasite can precede the initial onset of symptoms and subsequent diagnosis with schizophrenia, Yolken says. Because the U.S. military routinely tests its active personnel for toxoplasma, among other infectious agents, and stores blood samples in a central repository, researchers were able to determine the time line between infection and a diagnosis of schizophrenia.

kjmtchl "My initial response is that the abstracts I read are inferring causation from correlation." That sounds like 99.999% of the abstracts I've read concerning heredity and disease. Anyway according to the study on US military personnel symptoms occurred after infection with Toxoplasma.

Sorry this was broken into two posts. "the evidence for genetic mechanisms playing a major role is overwhelming." That's probably true for ALL disease including infectious disease. Scientists pinpoint flu gene http://www.telegraph.co.uk/health/3538487/Scientists-pinpoint-flu-gene.html "An unlucky combination of "vulnerable" genes could explain why some people recover from the flu overnight and others struggle to shake off the virus for weeks."

TGGP Greg Cochran is of course correct. Since Autism was mentioned the latest evidence strongly suggests an environmental trigger. For anyone who has at least some faith in natural selection this doesn't come as a surprise. http://www.sciencedaily.com/releases/2011/11/111107162734.htm "The study searched, on a genome-wide scale, for genes that show an abnormal epigenetic signature -- specifically histone methylation. Histones are small proteins attached to the DNA that control gene expression and activity. While genetic information is encoded by the (genome's) DNA sequence, methylation and other types of histone modifications regulate genome organization and gene expression. The study found hundreds of loci (the places genes occupy on chromosomes) across the genome affected by altered histone methylation in the brains of autistic individuals. However, only a small percentage -- less than 10 percent -- of the affected genes were affected by DNA mutations." In related news it's likely that Autism begins in the womb. http://www.sciencedaily.com/releases/2011/11/111108200720.htm "The researchers found that children with autism had 67 percent more neurons in the prefrontal cortex and heavier brains for their age compared to typically developing children. Since these neurons are produced before birth, the study's findings suggest that faulty prenatal cell birth or maintenance may be involved in the development of autism. Another possible factor that may contribute to the neuronal excess is a reduction in apoptosis, or programmed cell death, which normally occurs during the third trimester and early postnatal life."

kjmtchl Thanks for your response. This is why I assumed the Autism study pointed towards environment. "However, only a small percentage — less than 10 percent — of the affected genes were affected by DNA mutations." If less than 10 percent of the difference in genetic expression was the result of heredity doesn't that strongly argue for environment? I understand that Autism might get rolling because of a problem in the >10%. But all things being equal wouldn't the smart money bet that the trigger resides in the <90%?

The left wing may publicly embrace the theory of Tabula Rasa (blank slate) but they depend on the hard-wired trait of jealousy to get themselves into power.

If Autism is caused by heredity the genes involved must be spreading parabolically. A 2009 study published in the journal Epidemiology found that... "A study by researchers at the UC Davis M.I.N.D. Institute has found that the seven- to eight-fold increase in the number of children born in California with autism since 1990 cannot be explained by either changes in how the condition is diagnosed or counted — and the trend shows no sign of abating." "The incidence of autism by age six in California has increased from fewer than 9 in 10,000 for children born in 1990 to more than 44 in 10,000 for children born in 2000." http://www.sciencedaily.com/releases/2009/01/090108095429.htm