Scientists find similar brain matter loss in multiple mental disorders

Psychiatric disorders are widely perceived to be distinct, but new research indicates patients show similar gray-matter loss, which suggests that conditions like schizophrenia and depression have more in common than previously thought.

In a meta-analysis of 193 peer-reviewed papers, researchers at Stanford University School of Medicine analyzed whole-brain images from 7,381 psychiatric patients falling into six diagnostic categories: schizophrenia, bipolar disorder, major depression, addiction, obsessive-compulsive disorder and a cluster of related anxiety disorders. Using a control group of 8,511 healthy control subjects, they found that psychiatric patients had a similar loss of gray matter— the brain tissues that process information— in three brain structures.

The functions of these three parts of the brain are known, which gives researchers a lead onto what the commonality means.  These brain structures, while physically separate, participate in a circuit associated with high-level functions including planning and decision making, and are linked with emotional function. This so-called executive function is known to be perturbed across a range of psychiatric disorders.

“[It’s] the warning flag of the brain. Any time something unexpected happens, either for good or for bad … this flag goes up, the regions become active together, signaling the need to either increase control or focus on something and to increase the ability to regulate an emotion or thinking better … and you should pay attention to it,” senior author Dr. Amit Etkin, assistant professor of psychiatry and behavioral sciences at Stanford, told FoxNews.com.

Previous research has shown that these three brain regions are overactive in depressive patients, who are known to place importance on negative thoughts. But in disorders like schizophrenia, the regions are underactive, and patients don’t attribute importance to things they should, have problems with cognition, and may overemphasize their own thoughts.

“That concept of schizophrenia has been around for a while and linked to this kind of system, but people never really stepped back look at the forest for the trees and asked whether the same kind of process is in place across psychiatric disorders,” Etkin said.

Etkin’s research is unique because scientists looked at two disorders to study their similarities and determine how specific findings are for each diagnosis. Most other mental disorders are examined individually, with participants being compared to healthy, control individuals.

“The neat part about it … is the data are out there, it’s just about asking the questions, not coming up with a fancy new tool,” Etkin said. “Simply asking the question, and when you do, very interesting, surprising things come up.”

The team’s findings may lead to questions about diagnosing methodology, Etkin noted.

“As a clinician and neuroscientist, I would argue it validates a sense a lot of clinicians implicitly have, but our diagnosis system discourages— that there are a lot of similarities between the way patients with different disorders process  information,” he said. “[The findings] allow us to think a little bit more flexibly about our patients and focus on things that don’t fit into [Diagnostic and Statistical Manual of Mental Disorders (DSM)] categories.”

Psychiatric disorders are diagnosed using the DSM, which classifies diagnoses as distinct from each other. According to the American Psychiatric Association, DMS-5, the most recent edition, is “ the standard classification of mental disorders used by mental health professionals in the United States and contains a listing of diagnostic criteria for every psychiatric disorder recognized by the U.S. health care system.” There is no test, such as brain imaging, that reveals a patient’s diagnosis.

“The only information we use for diagnosis is what [the patient] reports; in other words, their symptoms and the way we observe them, sitting in front of them,” Etkin said.

While doctors have understood that psychological issues are related to brain function, the DSM has been used since its first edition in 1952 as the diagnostic standard, as it provided reliability for diagnoses that was not previously available, Etkin said.

One of the fundamental conclusions researchers drew from their findings is that doctors bring their assumptions with them of how they do things, how they see patients, and how they see disorders.

“But once you get to the level of the brain, you have to check and in fact question assumptions because they might mislead you,” Etkin said.

Finding this common brain circuit abnormality also allows for more flexibility in treatment tools, which are increasingly proving to be transdiagnostic themselves. For example, antidepressants are prescribed to patients suffering from the disease, but also for anxiety. Newer treatments, like transcranial magnetic stimulation (TMS), which is noninvasive, can target brain circuitry directly and can be used across mental disorders, Etkin said.

“If we get out of our box of thinking depression, schizophrenia, bipolar disorder are things that have one set of treatments and start to look at the boxes nearby and draw on tools from those other boxes, that can’t hurt our patient,” he said. “[It can] only help our ability to treat clinically but also from the research side, [entice] us to think differently about what kind of circuitry to try to intervene with to help people,” Etkin said.

While their findings showed little difference in brain structure between the studied disorders, it does not mean there is no difference between them, Etkin noted. Of the non-schizophrenic disorders, the brain structure of a depressive patient was the most different. Compared to other conditions, the amygdala and hippocampus, which are located deep in the brain, were more affected in depressive patients.

Whether the observed changes in brain matter are a result of cause or effect is unclear. But evidence suggests both come into play, researchers said.

“As disorders become more chronic and longstanding, there’s more loss in this circuit, but the function of these regions is also affected by things that put you at risk for psychiatric disorders. Certain genes, early life trauma, these things put one at risk for a range of disorders but also seem to affect function,” Etkin said.

The best  way to answer this cause-or-effect question is by developing tools that directly manipulate this brain circuit to find a way to fix activity, Etkin said. His team recently established a new consortium through the Stanford Neuroscience Institute to develop non-invasive tools that will translate into therapies capable of reaching anywhere in the brain.

Etkin likened finding these tools to using a hammer to hit a nail.

“The most critical element, we just don’t have a hammer,” Etkin said. “We design a hammer to hit the nail. In this case, the nail never actually had a proper hammer to be targeted with.”

The research was published in JAMA Psychiatry.