In a recent study, a team of researchers used brain imaging and machine learning to identify what they describe as six “clinically distinct biotypes” of depression and anxiety.
If future studies support their results, this could represent a groundbreaking development in the effort to create personalized courses of mental health treatment using brain imaging for patients with depression and anxiety.
The senior author, Leanne Williams, PhD, acknowledged the findings could elevate the role of science and technology in the treatment of common mental health disorders:
“To our knowledge, this is the first time we’ve been able to demonstrate that depression can be explained by different disruptions to the functioning of the brain. In essence, it’s a demonstration of a personalized medicine approach for mental health based on objective measures of brain function.”
Categorizing Anxiety and Depression
It’s common to think of anxiety and depression as distinct mental health disorders. But in clinical terms, these words are categories, not specific illnesses. For example:
- The anxiety disorders section of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes entries for 11 separate conditions.
- The depressive disorders section of the DSM-5 features criteria for 8 illnesses.
- Some of these condition descriptions include specifiers that further delineate them based on symptom type and severity.
The existence of multiple anxiety and depressive disorders highlights the fact that people who have the same general type of mental health challenge may have different experiences, in terms of both the symptoms they develop and the impact of the symptoms on their life.
The options also allow clinicians to provide precise diagnoses that reflect the nature and severity of individual symptoms.
However, despite 11 anxiety disorders and 8 depressive disorders, some patients present with symptoms that don’t fully align with any set of diagnostic criteria. And those with identical diagnoses may respond differently to various treatment approaches.
These reasons are why the recent brain imaging study may hold great promise for people who have anxiety and depressive disorders, as well as for those who treat them.
Understanding the Scope of the Problem
Anxiety disorders and depressive disorders are two of the most common types of mental health concerns in the United States:
- Experts estimate that around 1% of adults ages 18 and above in the U.S. will experience some type of anxiety disorder over the course of their lifetime. With a current adult population of about 258.3 million people, this means that more than 80 million individuals either have or will develop an anxiety disorder.
- The Centers for Disease Control and Prevention (CDC) reports that about 4% of adults in the U.S. have received a depression diagnosis at some point in their lives. This works out to about 47.5 million people.
Unfortunately, almost two-thirds of people with anxiety and half of those with depression aren’t receiving the treatment they need.
Also, studies indicate that as many as 60% of people who receive professional care for either anxiety or depression don’t achieve relief from their symptoms.
Williams, the study author we quote above, is both a professor of psychiatry and behavioral sciences and the director of Stanford Medicine’s Center for Precision Mental Health and Wellness. She acknowledges both the high failure rate of treatment and the difficulty of finding the right combination of medication and therapy to help patients in need.
Here’s her point of view:
“The goal of our work is figuring out how we can get it right the first time. It’s very frustrating to be in the field of depression and not have a better alternative to this one-size-fits-all approach.”
She continues:
“There are currently no tests available to help pinpoint what type of depression [people] have, or, I think especially importantly, what treatment might be most suitable for them. The current situation is we rely on a person to tell us what they’re experiencing and for the physician or therapist to observe symptoms and come to a diagnosis.”
Brain Imaging: Identifying Distinct Biotypes of Depression and Anxiety
In their report, Williams and her team wrote that their study focused on “the conceptualization of depression and anxiety as disorders of brain circuit function.”
The researchers used functional magnetic resonance imaging (fMRI) and machine learning to assess and compare brain activity in 938 adults:
- The study involved 801 adult participants who had one of the following conditions: major depressive disorder, generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD).
- The study also included a control group of 137 adults who had no history of mental illness.
- At baseline, none of the participants with anxiety or depression took medication for their disorders.
- The researchers studied participants’ brains during times of rest as well as while they completed tasks that involved cognition and emotions.
- The fMRI documented activity within six brain circuits: default mode, salience, attention, negative affect, positive affect, and cognitive control.
- For each brain circuit, the researchers measured 41 areas of activation and connectivity.
After conducting fMRI testing while participants were active and at rest, the researchers turned to machine learning to analyze and group the collected images. This led to the identification of six biotypes.
Currently, the somewhat unwieldy biotype naming convention uses the letters D, S, A, N, P, and C to refer to the six brain circuits they studied. The plus and minus signs in the first five biotypes represent the direction of the dysfunction in certain circuits. The X in the final biotype indicates that the researchers observed no prominent circuit dysfunction.
Brain Imaging and Biotypes Associated with Depression and Anxiety
C(A+):
258 participants exhibited this biotype, distinguished by hyperactivity within the cognitive control circuit. Individuals with this biotype may be more likely to experience anxiety, negative bias, and anhedonia (difficulty experiencing joy), while also struggling to properly assess threats.
D(C+)S(C+)A(C+):
The researchers found evidence of this biotype, which includes intrinsic connectivity in the default network and hyperconnectivity in the salience and attention circuits, in 169 participants. These participants were more likely to make errors in tasks that involved executive functions, but less likely to have difficulty with cognitive control tasks.
A(C−):
161 participants had this biotype, which involves reduced connectivity within the attention circuit. These individuals showed faster response time on certain tests, but they were also more likely to make errors on tasks that required sustained focus.
NS(A+)P(A+):
The 154 participants with this biotype exhibited heightened activity in the negative affect circuit while processing sad stimuli, and elevated activation of the positive affect circuit when processing happy stimuli. The research team noted that these participants were likely to experience “severe anhedonia … and ruminative brooding.”
NTC(C−)C(A−):
Only 15 participants showed evidence of this biotype, which involves minimal activation in the negative affect circuit when processing threats, lower levels of activity in the cognitive control circuit, and a reduced likelihood of ruminative brooding.
D(X)S(X)A(X)N(X)P(X)C(X):
44 participants had this biotype, which does not involve evidence of substantial dysfunctions in any of the circuit areas.
With the exception of major depressive disorder (MDD), the frequency of mental health diagnoses was fairly consistent among the various biotypes. The A(C−) biotype group included a higher-than-average concentration of people with MDD, while the D(X)S(X)A(X)N(X)P(X)C(X) group had far fewer cases of MDD.
Evaluating Treatment Effectiveness
In addition to identifying the six biotypes of depression and anxiety, Williams and her team also explored the effectiveness of certain medications and therapeutic approaches for people in each category.
To accomplish this, they randomly assigned 250 participants to either receive medication or engage in therapy. From this effort, they determined that:
- Participants with biotype C(A+) had the best response to venlafaxine (Effexor XR).
- Those with the D(C+)S(C+)A(C+) biotype responded best to a therapeutic intervention that included problem-solving and behavioral activation, which the researchers identified as I-CARE.
- Those with the A(C-) biotype received the least benefit from I-CARE.
Although the treatment component was not the main focus of the study, one of the co-authors emphasized the benefits of matching biotypes with treatment types. In the Stanford press release, University of Chicago professor Jun Ma, MD, PhD, observed the following:
“To really move the field toward precision psychiatry, we need to identify treatments most likely to be effective for patients and get them on that treatment as soon as possible. Having information on their brain function, in particular the validated signatures we evaluated in this study, would help inform more precise treatment and prescriptions for individuals.”
Moving Forward: The Near Future of Brain Imaging and Mental Health
While Williams, her team, and other experts see potential in the study of biotypes, they acknowledge that work remains before the current findings translate into treatment improvements.
For example, Dr Jonathan Alpert of New York City’s Montefiore Medical Center – who did not participate in this study – cautioned that the current research should “be thought of as a very preliminary study that needs to be replicated.”
And though James Murrough, MD, PhD, another non-participant, described this research as “super exciting,” he also noted that it is not enough to support dramatic improvements in personalized care:
Gianna Melendez
Jodie Dahl, CpHT