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Three new genetic studies are providing some tantalizing hints about what causes schizophrenia. The studies identified sections of our genetic code in which small changes can affect a person's risk of developing the disorder. These include stretches of code involved in brain development, memory and, surprisingly, the immune system.

NPR's Jon Hamilton reports.

JON HAMILTON: Schizophrenia has been incredibly hard to study. Kari Stefansson, who runs the Icelandic company deCODE Genetics, says that's because of its very nature.

Dr. KARI STEFANSSON (CEO, deCODE Genetic): It's a disease of thoughts and emotions, which is, you know, a disease of the two functions of the brain that define us as a species and define us as individuals.

HAMILTON: Decades of research have yet to find much difference between the brains of typical people and those with schizophrenia. So Stefansson and a consortium of researchers from around the world decided to look for subtle differences in people's genes. The result is three studies involving thousands of people that appear in this week's issue of the journal Nature.

Steffansson says one place the studies found a clue about what might be going wrong in the brains of people with schizophrenia was in a gene responsible for a protein called neurogranin. It can affect memory and thought.

Dr. STEFANSSON: So indeed, the neurogranin pathway could be one of the biochemical pathways that should lead to this disturbance of thought.

HAMILTON: But Steffansson says a more provocative finding is a genetic hotspot in a stretch of code that affects the immune system.

Dr. STEFANSSON: It raises the question that somehow the tendency to develop schizophrenia may have something to do with infections of mothers during pregnancy.

HAMILTON: The idea is that some families carry a genetic variation that affects the way the immune system responds to infection. If a mother gets the flu while she's pregnant, this immune response may affect her child's brain. But it's also possible that the immune system is involved in schizophrenia in some other way.

Dr. Tom Insel directs the National Institute of Mental Health, which helped fund all three studies, and so says the stretch of genetic coding affecting immunity is pretty mysterious.

Dr. TOM INSEL (Director, National Institute of Mental Health): In some ways, it's a little bit like the Bermuda Triangle of the human genome. It's an area with tremendous amounts of variability, and it's an area where we often find variation that's associated with many different disorders: diabetes, rheumatoid arthritis, Crohn's disease, many others.

HAMILTON: In those diseases, the immune system attacks the body's own cells, and that could also affect the brain. Researchers have suspected the immune system before, now they'll probably take a harder look. Insel says he's intrigued by the finding that some genetic variations linked to schizophrenia are also linked to depression and bipolar disorder.

Dr. INSEL: It suggests, potentially, that when we're talking about the genetic factors that contribute, what we're really thinking about are genetic factors that contribute to how a brain gets built.

HAMILTON: Which would mean problems in the brain start very early in life, even though the symptoms may not appear for decades.

Dr. Pamela Sklar from Harvard, an author of one of the new studies, says the results suggest just how many different systems in the brain may contribute to schizophrenia.

Dr. PAMELA SKLAR (Harvard Medical School): That's a hopeful finding because the implication is that there may be more places to intervene if we understand the biology.

HAMILTON: She says that understanding gets better with each new genetic study.

Jon Hamilton, NPR News.

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