No Link Between Schizophrenia Risk, Smaller Subcortical Brain Volumes

No evidence was found of genetic overlap between brain volume measures and risk of schizophrenia, according to research published in Nature Neuroscience.

This was the key finding in a worldwide collaborative study examining genes behind the development of schizophrenia.

Because brain volumes and schizophrenia are both affected by genetics, and because schizophrenia correlates with smaller subcortical brain volumes, the researchers investigated whether smaller brain volumes and schizophrenia share any genetic effects.

“We looked at subcortical volumes to determine whether the genes that increase risk for schizophrenia affect the hippocampus, thalamus and amygdala, and whether the genes that affect the volume of those areas increase risk for schizophrenia,” said Jessica Turner, PhD, associate professor of psychology and neuroscience at Georgia State University in a statement.

The study was between nearly 600 researchers from more than 350 institutions across the globe — a large-scale collaboration necessary in order to analyze results from common variant studies of schizophrenia (33 636 cases, 43 008 controls) and sample brain scans from 11 840 people worldwide.

“Unfortunately, our results indicate no overlap, so we are going to have to look elsewhere to find the genetic effects on brain measures causing the development of schizophrenia,” said Dr Turner. “But what makes this research so exciting is that the international scientific community is capable of working together on a massive scale, across country borders, to examine these questions that affect so many of us.”

These findings provide a proof of concept (based on a limited set of structural brain measures) and define a road map for future studies to investigate possible genetic covariance between brain structure or brain function and the risk for psychiatric disorders.

“We would rather have found that there is a set of genes that drive both the development of schizophrenia and a smaller thalamus, of course,” said Dr Turner. “But we will continue analysis on other parts of the brain, including the frontal cortex and temporal cortex, and a number of other approaches.”


Franke B, Stein JL, Ripke S, et al. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat Neurosci. 2016; doi:10.1038/nn.4228.