Innovative Genetic Study Uncovers Early Brain Development Link in Causing Schizophrenia

Mary-Claire King, Ph.D., Expert on Schizophrenia
Mary-Claire King, Ph.D.

In an important new study exploring the causes of schizophrenia, Brain & Behavior Research Foundation NARSAD Distinguished Investigator Grantee and Scientific Council Member, Mary-Claire King, Ph.D. of the University of Washington in Seattle and colleagues, used sophisticated genetic analysis to identify where and when spontaneous mutations in genes likely cause damage in the brain. They were able to determine that some people with schizophrenia may suffer from impaired birth of new neurons, or neurogenesis, in the front of their brain during prenatal development. Results of the study were published August 1 in the journal Cell.

The research team integrated genomic data with newly available online transcriptome resources that show where in the brain and when in development genes turn on. They compared spontaneous mutations in 105 people with schizophrenia with those in 84 unaffected siblings, in families without previous histories of the illness. The researchers identified mutations in 54 different genes in the subjects with schizophrenia. Further analysis indicated that these genes normally work together, particularly in the prenatal stages of brain development.

“Processes critical for the brain’s development can be revealed by the mutations that disrupt them,” explained Dr. King. “Mutations can lead to loss of integrity of a whole pathway, not just of a single gene. Our results implicate networked genes underlying a pathway responsible for orchestrating neurogenesis in the prefrontal cortex in schizophrenia.”

The findings support the long-standing notion that schizophrenia’s roots lie in early brain development. They also highlight the prefrontal cortex—the region of the brain that organizes information from other brain regions to coordinate executive functions like thinking, planning, attention span, working memory, problem-solving and self-regulation—as vulnerable in the disorder. Impairments in such functions that may start before the onset of symptoms in early adulthood, when the prefrontal cortex fully matures, appear to be early signs of the illness.

Read more about this research on the Schizophrenia Research Forum.

The Schizophrenia Research Forum is fully sponsored by the Brain & Behavior Research Foundation—a virtual community of scientists collaborating in their quest for causes, improved treatments and better understanding of schizophrenia.

Article comments

I am so sad my son won't advocate for his recovery and I fear I will outlive him can you help him and I? He needs to be hospitalized for life I can find help nowhere

I was diagnosed with Schizophrenia about 30 years ago. I find the research that's going on right now exciting. I wanted to thank the researchers and the Brain and research foundation for financing some of the research that's going on.

I would love to follow this research.

We have found that besides genetics the opioid pepides from gliadin,glutenin and casein , have a central role in schizophrenia (1-3). This is further supported by finding IgG and some IgA antibodies against the same proteins (4,5). For a detailed discussion and MS/MS see ref 6-8. Since these changes are also found before the manifest psychoses, the effect of opioids on CNS growth and development probably starts earlier causing well established prodromes

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2. Drysdake A et al (1985) Neuroscience 7:1567-1574
3. Cade R et al (2000)Nutritional neuroscience 3:57-72
4. Reichelt K.L and Landmark J (1995) Biol Psychiat 37:410-417.
5. Severence al (2010) Schizophrenia Res. 118: 210-247.
6. Reichelt K.L et al (1996) Prog. Neuropsychophamacol. and Biol Psychiat 20: 1083-1114
7. Tveiten D and Reichelt KL (2012) Open J Psychiat 2, 220-227
8. Reichelt K.L and Gardner, M.L.G.(2012) Open J Psychiat 2, 12-20;

I've always thought that something was wrong with my daughter when she was born. I was told she was colic but I had been around babies with colic and I knew her symptoms did not resemble colic. When she cried it was more like a scream, as if she were in great pain. She developed a hernia at 1 month and cried so fiercely that the thin skin under her tongue bled. When attempting to bottle feed her she would purse her lips so tight and refuse to drink. I was told to pinch the sole of her foot to get her to open her mouth. This only resulted in more screams. Then at approximately 2 months she started to behave "normally". She was diagnosed as schizophrenia at age 15 1/2. She is 54 y.o now and lives at home with me and attends a day program weekdays. Her response to hearing voices have become louder and angrier and is now diagnosed as schizoaffective disorder.

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