An important new meta-analysis of brain imaging research came out this week in JAMA Psychiatry, “Identification of a Common Neurobiological Substrate for Mental Illness” which highlights the importance of the insula and anterior cingultate in healthy brain function.
Neuroscientist News provides an effective overview of the results that came out of Amit Etkin’s lab at Stanford. I’ll then add in two caveats about the characterization of the deficits and the assumed biological causation that are needed in interpreting these results. Or, to be blunt, that social causes related to how we deal with mental illness in our modern societies have as much potential to explain these common biological differences, since it’s one of the main things that these patients share in common.
But first the overview.
We tried to ask a basic question that hasn’t been asked: Is there any common biological basis for mental illness?
To address that question, he and his colleagues pooled data from 193 separate studies containing, in all, magnetic-resonance images of the brains of 7,381 patients falling into six diagnostic categories: schizophrenia, bipolar disorder, major depression, addiction, obsessive-compulsive disorder and a cluster of related anxiety disorders.
Comparing the images with those from 8,511 healthy control subjects, the research team identified three separate brain structures, several centimeters apart from one another, with a diminished volume of gray matter, the brain tissue that serves to process information.
These structures — the left and right anterior insula and the dorsal anterior cingulate — are known to be parts of a larger network in the brain whose component parts tend to fire in synchrony. This network is associated with higher-level executive functions such as concentrating in the face of distractions, multitasking or task-switching, planning and decision-making, and inhibition of counterproductive impulses.
Gray matter loss in the three brain structures was similar across patients with different psychiatric conditions, the researchers found.
The abstract to the JAMA Psychiatry paper makes this same point:
Based on the voxel-based morphometry meta-analysis of 193 studies comprising 15 892 individuals across 6 diverse diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety), we found that gray matter loss converged across diagnoses in 3 regions: the dorsal anterior cingulate, right insula, and left insula.
By contrast, there were few diagnosis-specific effects, distinguishing only schizophrenia and depression from other diagnoses. In the parallel follow-up analyses of the 3 independent healthy participant data sets, we found that the common gray matter loss regions formed a tightly interconnected network during tasks and at resting and that lower gray matter in this network was associated with poor executive functioning.
So what is executive function in the eyes of Etkin? What is going on with these parts of the brain?
These structures can be viewed as the alarm bell of the brain, Etkin said. “They work together, signaling to other brain regions when reality deviates from expectations — that something important and unpredicted has happened, or something important has failed to happen.” That signaling guides future behavior in directions more likely to obtain desired results…
Among healthy people, gray-matter volume in the right and left anterior insula and the dorsal anterior cingulate correlated with performance on classic tests of executive function. Such a test might involve, for example, asking the test-taker to note the color of the word “blue,” displayed in a color other than blue, after seeing it briefly flashed on a screen.
Executive function always sounds to me, well, so executive. Like it’s a little capitalist dude there in your brain, telling you how to maximize profits and climb the corporate ladder. In other words, it’s a culturally-infused view of brain areas that we still don’t understand well. We know these areas are linked to social and emotional regulation, sense of self, coordination of behavior and integration of information, and the ability to make judgment calls.
I want to focus in on one line quoted earlier: “These structures — the left and right anterior insula and the dorsal anterior cingulate — are known to be parts of a larger network in the brain whose component parts tend to fire in synchrony.” Mental illness disrupts high-level synchrony between the brain and the world. This is the very stuff of social life. Social regulation and coordinated interaction with the world is key to how humans are humans.
Neuroscientist News points to a potential biological cause for the identified biological problem, highlighting a 2013 genetic study whose punchline is Common Genetic Factors Found in 5 Mental Disorders. You need to read a bit further into that research (like just to the bottom of the news article) to get to statements such as “causal factors haven’t yet been pinpointed” and “each of these genetic associations individually can account for only a small amount of risk for mental illness.”
For those of you interested in a more in-depth consideration of how genetics relates to mental illness, I recommend Kendler’s 2013 paper What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. As Kendler says elsewhere, “The impact of individual genes on risk for psychiatric illness is small, often nonspecific, and embedded in complex causal pathways. The phrase “a gene for” and the preformationist concept of gene action that underlies it are inappropriate for psychiatric disorders.”
But there is a specific and robust cause that can have a direct impact on brain function, particularly in the areas that Etkin and his colleagues have identified: How society deals with mental illness.
An alternative view is that societal reactions drive these patterns in the brain; that the lives of mental health patients become disorganized because of what happens through treatment (or lack thereof), the loss of social roles, and the inability to mesh with a capitalist and regulatory society. In other words, these common losses in brain grey matter can happen because of common societal causes.
The case for schizophrenia is clear. Caribbean people who move to the UK suffer much higher rates of schizophrenia than expected. And cross-culturally there are dramatically different ways of dealing with schizophrenia, such that symptoms can be less adverse in places like Chennai, India. But this biosocial view is not the type of approach being promoted by the Research Domain Criteria from the National Institutes of Mental Health, which views mental illness as biological.
One issue is that we don’t have good assessments that could link the type of problems in brain function identified by Etkin with the sorts of social causes that we know make a tremendous impact on people’s lives and their ability to effectively handle social regulation and coordinated interaction with a wider social world. By developing this approach, which could look more closely at how brain function interacts with daily function within the context of people’s lives, we might get closer to understanding what might be causing common patterns in mental illness and what we might do about as a society.