Tuesday, February 2, 2016

The Gene that Causes Schizophrenia? Easy there, big fella.

Scientific American says, Don't believe the hype.

Scientific American

"Researchers have identified a gene that increases the risk of schizophrenia, and they say they have a plausible theory as to how this gene may cause the devastating mental illness.
After conducting studies in both humans and mice, the researchers said this new schizophrenia risk gene, called C4, appears to be involved in eliminating the connections between neurons — a process called "synaptic pruning," which, in humans, happens naturally in the teen years.
It's possible that excessive or inappropriate "pruning" of neural connections could lead to the development of schizophrenia, the researchers speculated. This would explain why schizophrenia symptoms often first appear during the teen years, the researchers said.
Further research is needed to validate the findings, but if the theory holds true, the study would mark one of the first times that researchers have found a biological explanation for the link between certain genes and schizophrenia. It's possible that one day, a new treatment for schizophrenia could be developed based on these findings that would target an underlying cause of the disease, instead of just the symptoms, as current treatments do, the researchers said.
"We're far from having a treatment based on this, but it's exciting to think that one day, we might be able to turn down the pruning process in some individuals and decrease their risk" of developing the condition.""
By the way, imagine you are a healthy pre-teen genetically identified as being at higher risk for possibly developing schizophrenia (e.g., 500% increased risk!, i.e., a 5% chance versus everyone else's 1% chance) -- how excited would you be about taking a drug that is going to "turn down" the synaptic pruning in your developing brain?

Neuroscientists and genetic researchers are freaking crazy.

Here's another article on schizophrenia from 2014. Schizophrenia is polygenic, like other complex traits.

Scientific American

"[T]he biggest-ever genetic study of mental illness has found 128 gene variants associated with schizophrenia, in 108 distinct locations in the human genome. The vast majority of them had never before been linked to the disorder. This finding lays to rest any argument that genetics plays no role. [Who was suggesting that? Oh, yeah -- this guy.]
The study, published in July in Nature, is the result of a collaboration among more than 300 scientists from 35 countries, named the Schizophrenia Working Group of the Psychiatric Genomics Consortium. The researchers compared the whole genomes of nearly 37,000 people with schizophrenia with more than 113,000 people without the disorder, in a so-called genome-wide association study (GWAS). Genetic material, or DNA, is made up of a sequence of molecular pairs, thousands of which string together to form genes. The GWAS involves tallying known common mutations in these pairs, in people with and without a condition. Variants that show up significantly more often in people with the condition are said to be “associated” with it. The GWAS “potentially provides a more comprehensive view of the biological players in disease than previous genetic studies,” says Benjamin Neale of the Broad Institute in Cambridge, Mass., one of the study's lead authors.
The technique cannot identify the exact mutations that cause illness or even pinpoint specific genes. Rather it flags areas of the genome that contribute to risk. Genes in these regions warrant further investigation to uncover the biological processes underlying the condition. “We've prised open lots of windows for people to climb in and attack the biology of schizophrenia,” says Michael O'Donovan of Cardiff University in Wales, another lead author.
Treatments for schizophrenia have not advanced in more than 50 years, since the discovery of drugs that reduce the activity of the chemical messenger dopamine. A leading theory has therefore focused on overactive dopamine signaling. Sure enough, one of the identified regions contains a gene that produces the type of dopamine receptor that is blocked by antipsychotic drugs.
Another of the brain's chemicals, glutamate, has also received attention, but drugs that target it have not fared well in clinical trials. The new study implicated several glutamate-related genes. “This is important confirmatory evidence that glutamate is relevant to schizophrenia,” O'Donovan says. “Exactly how is another question.” Past drugs may have failed because, for instance, they targeted the wrong kind of glutamate receptor; the genetic results will help drug developers focus their efforts.
The meaning of some of the other findings is less clear. Immune system genes were implicated, as were genes previously associated with smoking. These findings do not necessarily mean that schizophrenia is related to immunity or that smoking causes schizophrenia. The area of the genome related to immunity contains hundreds of genes, some of which affect other aspects of biology. Genes can also perform distinct roles in various tissues. “A lot of immune system proteins probably have different functions in the brain,” O'Donovan says. The link with smoking is similarly opaque. For instance, one genetic variant might both predispose people to smoking and increase the risk of schizophrenia, without one causing the other.
An important overall conclusion is that schizophrenia is a complex trait like any other, but its complexity does not mean it will remain mysterious. Past GWAS research has led to breakthroughs for other health conditions with tangled genetic and environmental roots, such as diabetes and Crohn's disease, and experts believe that this study will do the same for schizophrenia. “That there are lots of small, common genetic effects, scattered across the genome, is itself an important finding,” Neale says. “There are many different biological processes involved.”

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