Neuroscience and Clinical Psychiatry

What does neuroscience have to offer clinical psychiatry? So far, not much, most practicing clinicians would probably answer. But neurobiological findings are already challenging our ideas about diagnosis, the mechanisms of psychiatric illness, and what transpires as we engage with our patients. While the complexity of the brain makes it unlikely that we will ever see a grand conceptual model comparable to Mendelian genetics or evolution, the coming years will bring an accumulation of discoveries that will transform the practice of psychiatry and other mental health professions. Already, neuroscientifically-derived explanations are powerful enough to generate hypotheses in our clinical work.

As a young medical student, I encountered the workings of the nervous system in classes on anatomy, physiology, developmental biology, and pathology. Today’s neuroscience is interdisciplinary, with contributions from genetics, paleontology, ethology, anthropology, psychology, computer science, philosophy, the social sciences, and engineering. The resulting flood of disparate and often confusing information can be difficult for clinicians to organize in a way that makes sense and generates useful questions.

For an aerial view of the field, I have found the National Institute of Mental Health’s Research Domain Criteria (RDoC) helpful. Organized around neurobiological constructs rather than diagnoses, the RDoC recognizes four overall domains for study: Negative Valence Systems, Positive Valence Systems, Cognitive Systems, and Systems for Social Processes. Each of these is broken down into constructs and subconstructs. The constructs for Negative Valence Systems, for example, are acute threat (“fear”), potential threat (“anxiety”), sustained threat, loss, and frustrative nonreward. Research in each of these areas is located at one or more of eight levels: genes, molecules, cells, circuits, physiology, behavior, self-reports, and paradigms. The program was designed to organize research funding and not as a clinical tool, and even my very cursory summary is too complex (and unfamiliar) to be of clinical use. But it does provide a matrix for thinking about all the new findings coming our way.

There has been debate recently about whether the RDoC is a better diagnostic system than the DSM. I do not see it as intending to function like a traditionally categorical diagnostic system. It seems more like the traditional “formulation” I learned as a resident, which organized the patient’s story into predisposing factors, such as family history or childhood stresses; the precipitating stress; and the type of reaction, which corresponded to today’s diagnosis. It was a way of organizing complex information in a logical sequence, in this case along the axis of time. The RDoc is much more complex and uses a two-dimensional matrix rather than the single dimension of time. And as critics have pointed out, one of its weaknesses is lack of explicit attention to the time course of psychiatric illness.

The NIMH is highlighting the neural circuit level of analysis, which has been called the “connectome.” Some even argue that psychiatric illnesses are best thought of as disorders of neural circuitry. While I expect many psychiatric problems will be best understood at some other level, neural circuits are simplifying metaphors which can help us think about some patients’ problems, as I illustrate below.

Does all this research to have anything to do with our clinical work? Some interesting surprises are already changing how we diagnose, understand, and relate to our patients.

At the level of diagnosis, the 2013 edition of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-V) separated compulsive behavior disorders from their traditional place among the anxiety disorders. The new category of Obsessive-Compulsive and Related Disorders was based on findings of different neurocircuitry and neurotransmitter systems, as well as differences in family history, phenomenology, and response to treatment. Body dysmorphic disorder and trichotillomania were moved to the new category, and new diagnoses of hoarding disorder and skin-picking disorder were created. I have found this new neuroscience-derived distinction between hoarding and obsessive-compulsive disorder especially helpful: the clinical pictures differ, and I am no longer surprised when a patient with hoarding does not respond well to treatments for OCD.

Researchers are beginning to uncover the pathophysiologies of depression, anxiety, and the psychoses, but the psychiatric disorder we best understand is addiction. All substances of abuse, as well as gambling, active the brain’s reward system—the mesolimbic dopamine pathway connecting the ventral tegmental area to the nucleus accumbens. This evolved to motivate adaptive behaviors such as eating, sex, and parental love by inducing pleasure. Addictive substances, however, trigger the release of two to ten times as much dopamine as naturally pleasurable activities, and often far more quickly. (The role of such “hijacking” of the reward system in other compulsions such as disordered gaming, sex, and eating is less well established.) For years I nominally subscribed to the “disease concept” of addiction, which Morton Jellinek proposed back in the 1940’s. While it made sense in a limited way, it didn’t convincingly explain addiction’s power to destroy lives. When I finally understood how substances activate our evolutionarily derived pleasure pathway, I had a credible explanation for the irresistible hold alcohol and drugs have on some people. Understanding that addicts are responsible for how they deal with addiction, but not for the disorder itself, I could discuss more confidently how they were handling their cravings and what help they might need.

For mental health clinicians interested in the powerful effect the therapeutic relationship exerts on healing, as well as other practitioners seeking to improve treatment outcomes, exciting research is emerging from social neuroscience, which looks at what happens in our brains when we interact with other people. Clinical empathy has now been dissected into four separate but interacting brain circuits: emotional sharing, cognitive perspective-taking, regulation of emotion, and wish to help (compassion). Helen Riess at the Massachusetts General Hospital has conducted sophisticated research on how “in-tune” psychotherapists are with their patients. In one case, simultaneous measurements of a therapist’s and patient’s skin conductance (a biomarker for anxiety) guided them to explore an area of hidden conflict for the patient, which led to major progress in treatment.

This emerging research will push clinical psychiatry beyond today’s unfortunately narrow emphasis on diagnosis as a guide to prescribing medication. New findings will challenge our concepts and treatments. Arguments and struggles for influence may echo those between psychoanalysts and psychopharmacologists in the 1960’s and 1970’s and over the DSM-III’s radically new approach in the 1980’s. Clinicians will have new conceptual models, new information on which to base treatment decisions, and new understanding of what is happening during treatment sessions. It will be an exciting and challenging time to practice psychiatry.

Future generations of mental health clinicians are likely to have grown up with a basic understanding of how the brain works—several organizations (including the National Institute on Drug Abuse) are developing neuroscience curricula beginning as early as kindergarten. Like Freud’s a century ago, neurobiological ideas will permeate culture, and with a sophistication well beyond today’s popular concepts of right- and left-brain and serotonin deficits. In college and graduate programs, tomorrow’s clinicians will acquire three- and four-dimensional models of the brain’s functioning which most of us today are incapable of comprehending. These will be the basis for new approaches to treating mental illness. Today’s clinicians can participate in this process by engaging with new findings as they emerge, trying out those that seem promising, and participating in the professional debate.

Further reading: NIMH Research Domain Criteria Matrix

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