People with Schizophrenia May Have Been Born with a Different Brain Structure

Schizophrenia is a mental illness with murky origins.

In 2014, scientists identified 108 locations where the DNA sequence in schizophrenic people tends to differ. But childhood trauma is also linked to a stronger incidence of the condition—so the exact relationship between biological and environmental factors is still very much unclear.

Now, though, a team of scientists has been able to directly observe and analyze biological properties of people with schizophrenia—bringing us slightly closer to a comprehensive understanding of the disorder. Kristen Brennand of the Icahn School of Medicine at Mount Sinai in New York and her colleagues took skin cells from 14 people with schizophrenia and reprogrammed them into stem cells that became nerve cells. What they found was that those nerve cells exhibited lower levels of a molecule called miR-9, which scientists have discovered plays a role in how neurons form in the fetus. Brennand and her team published their findings yesterday in the journal Cell.

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Fetuses that go on to develop schizophrenia may have low levels of a molecule called miR-9, which plays a role in how neurons form in the fetus’s brain.

Here’s Claire Wilson, reporting for New Scientist:

In further experiments, Brennand’s team showed that miR-9 might also affect how neurons migrate from where they form, next to the fetal brain’s central cavities, out to their final resting place in the brain’s outer layers.

They found that the “schizophrenic” nerve cells could not migrate as far in a dish as ones made from the cells of people who do not have the condition. This discrepancy vanished if levels of miR-9 were artificially restored. The signalling molecule seems to be a master switch that controls the activity of many genes affecting migration.

The study illustrates the possibility that people diagnosed with schizophrenia may have been born with brains that—due to the presence of genetic variants causing a dearth of miR-9—were structured differently from the brains of people with neither schizophrenia nor schizophrenia-like symptoms. On the other hand, a person born with typical levels of miR-9 could also acquire the illness later in life due to environmental factors. For now, the sample size on this particular study is too small to draw any grand conclusions—but it’s a start toward understanding the neurological foundations of this pervasive public health problem.