Genetic Variant May Boost Schizophrenia Risk in Adolescent Brain Development

January 23, 2019

By David Douglas

NEW YORK—An imaging genetics study of brain structure in adolescents suggests that a missense mutation in the zinc-transporter gene SLC39A8, implicated in schizophrenia, affects gray matter volume in the putamen, according to a multinational group of researchers.

The study, Dr. Qiang Luo told Reuters Health by email, "has found a new pathway of genetic risk disrupting the development of adolescent brain and thereby further increasing the risk of mental illness, which will hopefully help reveal the pathogenesis of schizophrenia and provide new possibilities for the theoretical study of prior intervention before the emergence of clinical symptoms."

In a January 16 online paper in JAMA Psychiatry, Dr. Luo of Fudan University, Shanghai, China, and colleagues note that "deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms."

To help identify genetic variants associated with brain structures, the researchers assessed 1,721 healthy 14-year-olds using brain imaging and genome-wide association studies. Also involved was a sample of 8,690 healthy adults to provide independent replications across life span.

Dr. Luo said in a statement, "One of the major difficulties this kind of research needs to overcome is that genetic control of brain changes with age. Previous studies have not strictly controlled the confounding effect of age on the gene-brain association, and this confounding effect may blur such association."

The team found significant association between a missense mutation in SLC39A8 and greater gray matter volume in the putamen, an association that was confirmed across the life span. However, this association was significantly weakened in a clinical sample of 157 patients with schizophrenia and 149 unaffected siblings.

Together, say the investigators, "these findings provide a new and testable hypothesis of an interaction between the pathology of schizophrenia and the mechanism determining the putamen volume."

They conclude, "Given that the major function of the SLC39A8 gene is accessible to pharmacologic manipulation we believe that these results are crucial for discovering novel treatment for schizophrenia."


JAMA Psychiatry 2019.

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