Does it begin before birth? Thierry Berrod, Mona Lisa Production/Science Photo Library
People who develop schizophrenia may have been born with brains with a different structure. The finding adds further support to the idea that genetics can play a key role in schizophrenia, which involves delusions and hallucinations and is often a lifelong condition once it develops.
Schizophrenia has been the subject of a fierce nature-versus-nurture debate: childhood abuse is linked with a raised risk of the condition, but 108 genes have been implicated, too.
Probing the biology of schizophrenia is difficult because brain tissue sampled from people with the condition is rarely available to study. Kristen Brennand of the Icahn School of Medicine at Mount Sinai in New York and her colleagues got around this by taking skin cells from 14 people with schizophrenia, and reprogramming them into stem cells and then nerve cells.
They found that on average these nerve cells had lower levels of a signalling molecule called miR-9 than similar cells developed from people who do not have schizophrenia. A small string of nucleic acids, miR-9 can change the activity of certain genes and is known to play a role in how neurons develop in the fetus.
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.
In people with schizophrenia, symptoms tend to appear in the teens or 20s, perhaps triggered by something going wrong with the normal process of neuronal pruning as the brain matures in adolescence. Researchers suspect that this may arise from problems that begin in the womb and then stay silent through childhood.
The new finding suggests that, at least in some people, genetic variants reduce levels of miR-9, which causes problems with nerve cell migration or development. “Even before your child is born the genetics have already started to do their work,” says Brennand.
Team member Mads Engel Hauberg of Aarhus University in Denmark says schizophrenia is thought to be about 80 per cent heritable. “People with a severe burden of genetic variants could develop schizophrenia in the absence of any environmental factors; people with a less severe burden, on the other hand, could potentially stay healthy unless exposed to environmental factors such as traumatic life events.”