Major mental illnesses share unexpected gene activity

Several psychiatric disorders – autism, schizophrenia, bipolar disorder and depression – share patterns of gene activity, an international team of scientists has found. 

The team used samples from 700 human brains to study the transcriptome, a method of measuring gene activity by assessing which parts of the DNA are transcribed, of psychiatric patients with each of the disorders, as well as those with alcoholism. The team took post-mortem samples from the cerebral cortex, the outer layer of the brain, to measure similarities and differences in which genes were transcribed to RNA. They compared the psychiatric patients' transcriptomes with healthy people, and patients with inflammatory bowel disease.

The team expected to find that conditions such as bipolar disorder and depression would be more similar than other conditions as patients affected by them show similar symptoms. However, they found that bipolar disorder and schizophrenia had similar gene activity patterns, as did autism and schizophrenia, but found no shared pattern between alcoholism and the other conditions studied. The work was published in Science.

'This study demonstrates for the first time that gene expression can be used to robustly define cross-disorder phenotypes that are shared and distinct,' said senior author Dr Daniel Geschwind, professor of neurology, psychiatry and human genetics at University of California, Los Angeles. 'These findings provide a molecular, pathological signature of these disorders, which is a large step forward.'

Previous studies had already found that mental illnesses shared some genetic variants, but the current study takes that further and shows that gene activity is also similar.
 
'This is not what clinicians would've expected,' said Dr Kenneth Kendler at the Virginia Commonwealth University in Richmond, Virginia, who was not involved in the study. 'This is changing fundamental views about the nature of psychiatric illness. It certainly suggests the idea that these are sharply different kinds of disorders is not valid,' he told Science.

The findings on shared gene activity can lead to diagnostic tests for mental illnesses, and has already led to a trial for a new autism treatment.

The work has been hailed as a breakthrough but Dr Geschwind acknowledges more work needs to be done to understand the similarities. 'We now have to understand the mechanisms by which this comes about, so as to develop the ability to change these outcomes.'