Researchers have mapped the brain volumes of people with common mental illnesses and found that despite individual differences between people with the same diagnosis, common, connected brain areas are affected. The findings may be useful for developing targeted treatments for different disorders.
Despite thousands of neuroimaging studies and meta-analyses looking at brain changes associated with specific psychiatric diagnoses, the causal mechanisms underpinning mental illness are still tricky to pin down. Part of this may be due to a reliance on group averages rather than focusing on the differences seen in individual cases.
A new study led by researchers from Monash University has mapped changes in the brain volume of 1,294 people diagnosed with one of six psychiatric disorders and found that while there is much diversity between individuals, there are also commonalities that may present a useful target for treatment.
“Over the past few decades, researchers have mapped brain areas showing reduced volume in people diagnosed with a wide variety of mental illness, but this work has largely focused on group averages, which makes it difficult to understand what is happening in the brains of individual people,” said Ashlea Segal, lead author of the study.
The question the researchers ultimately set out to answer is this: if individuals diagnosed with a mental illness exhibit different brain changes that produce different symptoms, is there a common, connected brain circuit or network shared by people with that diagnosis?
The researchers used statistics to map regions in the brain showing unusually large or small volumes in people diagnosed with schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD).
“We used a statistical model to establish expectations about brain size given someone’s age and sex,” said Alex Fornito, one of the study’s corresponding authors. “We can then quantify how much an individual person’s brain volume deviates from these expectations, much like the growth charts commonly used for height and weight in pediatrics.”
Statistics aligned with previous studies that had found that brain volume deviations varied widely between individuals.
“We confirmed earlier findings that the specific brain regions showing large deviations in brain volume vary a lot across individuals, with no more than 7% of people with the same diagnosis showing a major deviation in the same brain area,” Fornito said. “This result means that it is difficult to pinpoint treatment targets or causal mechanisms by focusing on group averages alone. It may also explain why people with the same diagnosis show wide variability in their symptom profiles and treatment outcomes.”
The researchers then examined whether areas of the brain that displayed large volume deviations were connected and found that these deviations were embedded within common brain circuits in up to 56% of cases.
“Because the brain is a network, dysfunction in one area can spread to other, connected sites,” said Segal. “We found that, while deviations occurred in distinct brain regions across different people, they were often connected to common upstream or downstream areas, meaning they aggregated within the same brain circuits.”
The researchers say this connection explains why, for example, two people with the same diagnosis have more symptoms in common compared with two people with different diagnoses.
“It’s possible that this circuit-level overlap explains commonalities between people with the same diagnosis, such as, for example, why two people with schizophrenia generally have more symptoms in common than a person with schizophrenia and one with depression,” said Segal.
While the study’s findings potentially identify new targets for treatment based on diagnosis, the researchers say there are limitations to how successful the treatments might be.
“We found that certain specific brain circuits were preferentially involved in some disorders, suggesting that they are potential treatment targets,” Segal said. “However, our findings suggest that these targets will only be appropriate for a subset of people. For instance, we found evidence that brain circuits linked to frontal areas were preferentially involved in depression. These circuits are commonly used as targets for non-invasive brain stimulation therapies, but our data suggest that they may only be effective targets for around a third of people.”
Nevertheless, the approach taken by the researchers opens up new opportunities for mapping brain changes in mental illness.
“The framework we have developed allows us to understand the diversity of brain changes in people with mental illness at different levels, from individual regions through to more widespread brain circuits and networks, offering a deeper insight into how the brain is affected in individual people,” Fornito said.
The study was published in the journal Nature Neuroscience.
Source: Monash University
