Brain features associated with neonatal risk for schizophrenia

Differences in neonate brains

Writing in the American Journal of Psychiatry, John Gilmore and colleages reported that the size and structure of the brains of newborn boys—but not girls—who are at risk for developing schizophrenia differ from those of their peers. Using multiple scanning methods at different times during gestation and infancy, the researchers compared the brains of offspring of mothers who have schizophrenia to the offspring of mothers who do not have schizophrenia; they found that high-risk boys had larger brains and larger lateral ventricles than baby boys whose mothers did not have psychiatric illness.

Because the risk of developing schizophrenia is much greater for close relatives of schizophrenics, the differences between the groups provides a strong indicator of later potential development of disease. Professor Gilmore wondered “Could it be that enlargement is an early marker of a brain that’s going to be different?”

“It allows us to start thinking about how we can identify kids at risk for schizophrenia very early and whether there [are] things that we can do very early on to lessen the risk,” said Doctor Gilmore, who is also director of the University of North Carolina Schizophrenia Research Center.

Objective: Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia.
Method: Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts.
Results: Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties.
Conclusions: Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors’ knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.

Gilmmore, J. H., Kang, C., Evans, D. D., Wolfe, H. M., Smith, J. K., Lieberman, J. A., Lin, W…. & Gerig, G. (2010). Prenatal and neonatal brain structure and white matter maturation in children at high risk for schizophrenia. American Journal of Psychiatry, advance publication 1 Jun 2010 doi: 10.1176/appi.ajp.2010.09101492; PMID: 20516153

There will be much more work needed before researchers can be certain that this finding will help predict childhood schizophrenia. Not only are fairly direct replications needed, but also follow-along studies are important (they’ll permit researchers to learn whether the predictions hold over a longer term and with different behavioral outcomes). If the predictors are strong, then another question that will have to be studied is how much of a difference matters. The clinical applications of this finding are a long time in the future, even though it’s a fascinating finding.

In short, parents shouldn’t start measuring their babies’ heads. Teachers shouldn’t look at children and think, “Ahh. I knew it. He’s got a big head.”

Learn more about the UNC research program on early brain development and schizophrenia. Professor Gilmore was quoted in a press release from Newswise. See the Newswise press release about the study.

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