Schizophrenia, bipolar disorder and autism seem to have some similar effects on the brain. Analysing gene activity is taking us a step closer to understanding what causes such mental health conditions.

Unlike cancer or Alzheimer’s, say, for which underlying biological causes have been identified, psychiatric disorders and some developmental disorders are defined by behavioural symptoms. We know that people born with certain gene variants can be more likely to develop schizophrenia, bipolar disorder and autism-like behaviour, but we don’t know what these genes might be doing, and how they might put people at risk.

“The brain is an incredibly complex organ – if something is out of whack, something else can step in to compensate, so it’s very difficult to identify the fundamental problem,” says Jehannine Austin at the University of British Columbia in Canada.

Now it seems that the way some brain cells work is changed in similar ways in these conditions. Daniel Geschwind at the University of California, Los Angeles, and his team have been studying brain tissue donated by people who had such brain-related conditions when they died, and working out how active different genes were in their brain cells.

Overlapping activity
The group looked at tissue from people who had any of five diagnoses: autism-like conditions, schizophrenia, bipolar disorder, depression and alcoholism. “We found substantial overlap,” says Geschwind. “This work shows that using molecular features we might be able to get a good picture of these disorders, and develop targeted therapies.”

The greatest overlap was seen between samples taken from people with autism, schizophrenia and bipolar disorder, although these conditions also showed a smaller degree of overlap with depression.

This mirrors what doctors have seen across generations of families, says Austin. “We tend to see disorders like depression, anxiety and bipolar disorder all in the same family,” she says.

Geschwind’s analysis reveals why some of these conditions overlap. In the brain, star-shaped cells called astrocytes help neurons grow. In people with autism, schizophrenia and bipolar disorder, genes involved in controlling how these astrocytes function seem to be more active.

Depression and addiction
But each condition also had unique elements. Brain samples from people with depression, for example, showed signs of stress and inflammation. This chimes with the growing body of evidence suggesting that brain inflammation plays a role in mood disorders, and that anti-inflammatory medicines might help treat depression.

Heather Whalley of the University of Edinburgh, UK, hopes studies like these will go on to help identify subcategories of depression. “Depression is such a heterogeneous disorder, it’s likely there are different subtypes with different mechanisms,” says Whalley. “It might make it easier to identify treatments.”

Geschwind’s team found no overlap between alcoholism and the other conditions they studied. This might be because the study only included a small number of people with alcoholism, says Austin. But it might hint that addictions work in a different way, says Kevin McGhee at Bournemouth University, UK.

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