Two schizophrenia types discovered

An international research team has discovered there are two distinct neuroanatomical subtypes of schizophrenia.

After analysing the brain scans of 307 patients from three continents, they found that nearly 40% had the same volume of grey matter as you find in a healthy brain, rather than the expected lower volumes. 

Accounting for these differences, they say, could inform more personalised treatment options.

“In the future, we’re not going to be saying, ‘This patient has schizophrenia’, we’re going to be saying ‘this patient has this subtype’ or ‘this abnormal pattern’ rather than having a wide umbrella under which everyone is categorised,” says principal investigator Christos Davatzikos from the University of Pennsylvania, who worked with colleagues from the US, Germany and China. 

Their findings are published in the journal Brain.

Schizophrenia is poorly understood, Davatzikos suggests, in part because research has tended to compare damaged to healthy brains without taking account of the disorder’s heterogeneity: symptoms and responses to treatment vary greatly from patient to patient. 

His team used HYDRA, a machine learning method he and colleagues developed, to analyse brain scans, which helped identify “true disease subtypes” by limiting the influence of confounding variables, such as age, sex and imaging protocols. 

“This method enabled us to sub-categorise patients and find how they differed from the controls while allowing us, at the same time, to dissect this heterogeneity and tease out multiple pathologies, rather than trying to find a dominant pattern,” Davatzikos says. 

The researchers found that 115 of their 307 patients did not have the typical pattern of reduced grey matter volume that has been historically linked to schizophrenia. 

In fact, their brains showed increases of volume in the middle of the brain, in an area called the striatum, which plays a role in voluntary movement. The researchers aren’t sure why.

They also aren’t willing to speculate as to why an entire subset of patients with schizophrenia had brains that resembled healthy people

“This is where we are puzzled right now,” Davatzikos says. “We don’t know. What we do know is that studies that are putting all schizophrenia patients in one group, when seeking associations with response to treatment or clinical measures, might not be using the best approach.”

Colleague Daniel Wolf, a psychiatrist, says current treatments for schizophrenia “work really well in a minority of people, pretty well in most people, and hardly at all in a minority of people”. 

“We mostly can’t predict that outcome, so it becomes a matter of trial and error. Now that we are starting to understand the biology behind this disorder, then we will hopefully one day have more informed, personalised approaches to treatment.”