Avoidable human suffering accrues as a result of the absence in Mental Health Care of the type of precision diagnosis and personalized treatment seen in other medical disciplines such as cardiology and oncology. And why should that be, given that Major Depressive Disorder (MDD) is the leading contributor to the global burden of disease? Major Depressive Disorder is but one mental illness, but is the most prevalent. 16 Million Americans are afflicted each year.
In
(2022, American Psychiatric Press Association) Leanne M. Williams, Ph. D, and Laura M. Hack, MD., Ph.D review the limitations and pitfalls of the current state of diagnosis and treatment, and provide a roadmap to a better future where neuroscience, machine learning, genetics, blood markers (bio markers), and neuropsychological testing for cognitive function all come together with patient presentation and experience to provide a deeper taxonomy of mood disorders to take the guesswork out of understanding the type of distress the patient is experiencing, what’s causing it, and what will help. They argue that is increasingly possible to fit treatment to specific patients, rather than a general diagnosis.
Williams and Hack have curated, edited, contextualized, and woven together a compendium of articles which lead us on a journey from the present state of trial and error to precision, personally tailored, measurement-based care (from the title) starting with the explosion of our knowledge and understanding of the brain that comes from the availability of functional Magnetic Resonance Imaging (fMRI) of the brain.
fMRI improves on MRI in that we can see not only brain anatomy, but brain activity — what is actually going on in the brain as the different structures interact with one another in processing experience, and shaping behavior.
Witnessing these patterns of interactions through processing circuits, and associating them with patient experience and cognitive testing results allows researchers (and later, providers) to enrich the taxonomy of depressive and anxious sub-types by understanding what’s working and not working within an individual brain.
Williams and Hack and the many contributors to this compendium categorize the disruptions to neural circuits into clinical sub-types which are associated with how patients feel, think, and perceive themselves. For example, anhedonic subtype of depression (absence of anticipated or experienced pleasure, or motivation to seek it) is shown in fMRI imaging as a disruption in the “reward circuit,” in which the striatum brain structure is observed as hypoactive. Understanding what’s happening from a brain activity perspective allows a treatment team to make a much more reliably effective treatment plan, incorporating what medications, cognitive behavioral talk therapy tools, or other interventions — Transcranial Magnetic Stimulation (TMS), for example.
In lived experience, depression and anxiety symptoms make it harder for depressed and anxious patients to access and benefit from treatment. Hopelessness that anything can help them, belief that life is simply sad and/or perilous, suspiciousness toward providers and treatments, and feelings of their own inadequacy to most tasks including sticking with therapies that don’t provide quick wins all create and reinforce barriers to getting better.
Every day without effective treatment leads to longer, more intense suffering, and also further damage to the material circumstances of patients’ lives. Most every therapist wishes we could short-circuit this “vicious cycle” which is the product of the historic and contemporary hit and miss approach to choosing a treatment strategy based exclusively upon a provider’s interpretation of a patient’s description of their experience.
Unfortunately, such reliance on experiential trial and error that represents the historic and present day approach to finding a therapy that works for a particular patient reinforces this vicious cycle. Evidence shows that with each unsuccessful treatment attempt, the likelihood of success of a future treatment diminishes. This contradicts the belief that trying something inefficient is universally best for the patient.
In the simplest terms, we make an educated guess about what might work to relieve depression or anxiety, and sometimes, we get it wrong, wasting patients’ time and resources, and actually harming the patient by virtue of the delay and “defeat” reinforcing the feelings of worthlessness, hopelessness, and suspicion.
Along with understanding mental health problems through the lens of brain circuit disruptions, readers are treated to explorations of how the clinical picture and prognosis is enriched through the use of blood markers, notably inflammation and genetics (pharmacogenetics). All of this is subjected in the written material to a comprehensive roadmap of integration, translation to treatment, and dissemination to broader practice through training of clinicians.
From exposure to the material and research subjects who I counseled, I noticed the following “side effects” that found their way into the therapy suite with me:
First and foremost, the deep sense of empathy almost every patient experiences when their pain is described so precisely as it is when we bring the richness of the deeper taxonomy of mood disorders and how they work – and the resultant deepening of the therapeutic alliance, which is so influential in determining treatment outcomes,
The relief of shifting from shame to the more empowering cognition, “It’s not my fault, but I can understand it and believe we can fix it together .” This is a triple win inasmuch as such self-efficacy is foundational for change, and feeling relief of the shame associated with the stigma of depression provides insight that reduces feelings of worthlessness, a feature of depression for many.
Insights patients gain about their cognitive biases after going through the cognitive testing portion of the study.
The reduction of stigma and personal undermining feelings and thoughts of worthlessness when patients, and in some cases their families, are able to get a glimpse of the biological nature of their mood disorders
The feelings of hope and empowerment that is afforded by understanding causes and having a plan for working together to address those.
For scientists, and engineers, relating symptoms and difficulties they are experience to processing circuitry and chemistry provides an acceptable and culturally appropriate/familiar lexicon for explaining their clinical and life experience, which is easier to accept as valid, compared to an initial focus on feelings, which many devalue, even if they are effecting functioning. and
After patients have been through the assessment, they are much more aware of the role of cognitions and biases, realizing that the tests related to emotional recognition, cognitive functioning, attention/focusing; at-rest, and in task mode were in different degrees frustrating, easy, difficult, and fun, and they are actively curious about themselves in a compassionate way, which is both a good result generally, and also improves their ability to work on gaining insight, changing behavior, and having and interpreting new experiences.
As a Marriage and Family Therapist not qualified to prescribe medications, in addition to benefitting from the aforementioned patient experiences, my work with patients benefits from having learned a bit about these neuroscience insights.
For example, when I am teaching patients mindfulness techniques, I automatically find myself pointing to my amygdala and then pointing away from my head as I explain how mindfulness is about redirecting attention from unproductive, worrying thoughts. Visualizing it in this way, and rudimentary understanding of brain structures helps patients understand much more quickly how the technique works, and to accept that while they don’t have control of the distorted thoughts that are initially generated in response to perceived threat, that they do have dominion over where they direct their attention. Not understanding this has been a frustration for many patients who expect meditation to “clear the mind.”
Similarly, when working with thought distortions, I point to the amygdala, and demonstrate “dragging” the negative, unproductive thoughts around to the prefrontal cortex where they can be evaluated, and in some cases, translated into emotionally intelligent choices and actions, which are also associated with decreased agitation. I encourage patients to “drag it with me,” (mirror my gesture of pinching the thought near the back of the head and dragging it around to the forehead), and they are generally receptive, and this kinesthetic experience seems to help them with the skill of cognitive reappraisal.
I also talk to them about the striatum role in motivation and pleasure, and we join each other in visualizing “squeezing the sponge” -- then making a fist as if squeezing-- that contains dopamine to address the anhedonic challenges with anticipating pleasure and experiencing it, and finding energy and motivation to pursue pleasurable and productive activity.
Understanding the role that inflammation can have in treatment resistant or refractory depressive episodes has helped patients find motivation to stick with diet and exercise programs as part of their total treatment plan.
Reading Williams and Hack can be simultaneously thrilling, and dauntingly slow-going as there is a specific lexicon that derives from the studies, and the terms you just learned about on one page are used in passing on the next. Few of us have a level of expertise in all the disciplines that come together in this scientific inquiry to make quick work of understanding the complexity of their coming together on these pages. This seemingly arcane vocabulary is a necessary feature of this kind of writing, because unlike language in daily use, the lexicon has to be very specific to be accurate.
That said, not a word is wasted.
While the book acknowledges the usefulness of Cognitive Behavioral psychotherapeutic techniques (CBT), and makes recommendations about incorporating Reinforcement Learning (RL) Theory, I hope future editions and research will take a deeper dive into the role of talk therapy as part of a holistic personalized, gold standard of treatment.
It is my fond hope that this research continues, attracts strong funding, and leads to more publication, translation to clinical practice, and wide adoption of the learnings. The authors’ vision of developing translation from the hard science of brain activity, and biomarkers, subjected to the computational models to guide application of neuroscience to clinical application will be a game changer in reducing suffering and disease burden by bringing the right treatment for the correctly-diagnosed clinical picture to the right patients through easy to implement recommendations of specific, personalized drug, cognitive behavioral, and other therapies which are dramatically more reliably effective in each case.
I can only give the highest possible recommendation that every clinician, as well as curious patients read it. Slowly. Though it’s just 248 pages, you’ll want to read a page, digest it, and reread it.
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