Nancy A. Melville

March 30, 2015

COLORADO SPRINGS, Colorado — Neonates of mothers with schizophrenia or bipolar illness show abnormalities in the amygdala in the earliest stages of brain development that are consistent with alterations associated with schizophrenia, according to new research.

"Abnormal amygdala functional connectivity is present in infants at high risk for schizophrenia shortly after birth," said lead author John H. Gilmore, MD, director of the Center for Excellence in Community Mental Health at the University of North Carolina at Chapel Hill.

"With the bulk of structural and functional development in human brains tending to be done by 2 years of age, I think it is very important to identify infants at risk very early in life and develop early intervention strategies."

Abnormalities in functional connectivity of the amygdala-prefrontal cortex have been documented in adults with schizophrenia, as well as in adolescents with a risk for psychosis, and are considered the basis for emotional processing deficits.

In an effort to determine whether such abnormalities are seen even in early life in neonates of mothers with schizophrenia, who are therefore at high risk themselves, the investigators evaluated resting state functional magnetic resonance imaging of 15 infants of mothers with schizophrenia, 20 infants of mothers with bipolar disease, 20 infants of mothers with mood disorder, and 20 infants of mothers with no major psychiatric illness, who served as control participants.

The findings were presented here at the 15th International Congress on Schizophrenia Research (ICOSR).

Important Insights

Although amygdala connectivity was well developed at birth in all infants, among infants of mothers with schizophrenia, the left amygdala had greater hyperconnectivity to the right dorsal prefrontal cortex compared with infants in the other high-risk groups, which tended to have a negative correlation.

"These findings are consistent with studies in adults," Dr Gilmore said.

In addition, a secondary analysis showed that children of mothers with schizophrenia had reduced thalamic–mid cingulate connectivity compared with children in other high-risk groups and with children in the control group, in whom positive connectivity was found. This is also consistent with multiple studies showing reduced thalamocortical connectivity in adults with schizophrenia.

"These findings indicate that these abnormal functional circuits associated with schizophrenia look like they likely arise during prenatal and early neonatal brain development," Dr Gilmore said.

"The study suggests that it may be possible to develop imaging-based early identification of risk for later psychiatric illness at the earliest stages of postnatal life," he added.

The findings offer important insights into the patterns of schizophrenia as the brain develops, said Deanna Barch, PhD, chair of the Department of Psychology, Washington University in St. Louis, who moderated the session.

"This is one of the first set of results looking at in vivo brain imaging analysis in the infant offspring of individuals with schizophrenia," she told Medscape Medical News.

"It is critical, as it suggests brain differences that are present essentially from birth, implicating neurodevelopment alterations occurring during gestation, either due to genetics or in utero environment or both."

In terms of how such information could be used to prevent psychosis later in life, however, much more needs to be understood, she noted.

"There are, of course, general things that you would want to recommend for children at risk for any psychiatric disorder, but we don't have evidence about specific interventions for children in this age range that are preventative specifically for psychosis."

Dr Gilmore and Dr Barch report no relevant financial relationships.

15th International Congress on Schizophrenia Research (ICOSR). Abstract 2088024. Presented March 29, 2015.

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