Friday, November 05, 2010

Research Domain Criteria for Classifying Mental Disorders

"The more a delusion is investigated, the more understandable and less bizarre it becomes, often interwoven with the very individual patterns of experiencing relationships, adversities and suffering, and finally, for every delusional content, as bizarre and remote as it may appear, there may be a cultural niche, in which the same content may be considered legitimate and reasonable."

-Pfeifer (1999), Demonic Attributions in Nondelusional Disorders.

What is psychopathology?

According to Wikipedia,
Psychopathology is the study of mental illness, mental distress and abnormal, maladaptive behavior. The term is most commonly used within psychiatry where pathology refers to disease processes. Abnormal psychology is a similar term used more frequently in the non-medical field of psychology.
But what is "abnormal, maladaptive behavior"? That's such an enormously complicated question that I wouldn't know where to begin. In fact, as a non-clinician I think it would be rather pompous of me to try and define the parameters of what is (and is not) pathological. For that I refer the reader to the ICD-10 or the Diagnostic and Statistical Manual of Mental Disorders (DSM), both voluminous (and imperfect) attempts to diagnose mental illness based on signs and symptoms. As most of you know, the DSM-IV is currently in the process of being revised. The DSM-5 will be the controversial new revision, with a (delayed) publication date of May 2013.

The National Institute of Mental Health (NIMH) in the U.S. is starting to take a different approach to the classification of psychiatric disorders, one that incorporates dimensions of observable behavior as well as neurobiological measures. The aim of the Research Domain Criteria (RDoC) project... to define basic dimensions of functioning (such as fear circuitry or working memory) to be studied across multiple levels of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined.
The RDoC draft outlines some problems with the present DSM approach:
However, in antedating contemporary neuroscience research, the current diagnostic system is not informed by recent breakthroughs in genetics and molecular, cellular and systems neuroscience. Indeed, it would have been surprising if the clusters of complex behaviors identified clinically were to map on a one-to-one basis onto specific genes or neurobiological systems. As it turns out, most genetic findings and neural circuit maps appear either to link to many different currently recognized syndromes or to distinct subgroups within syndromes. If we assume that the clinical syndromes based on subjective symptoms are unique and unitary disorders, we undercut the power of biology to identify illnesses linked to pathophysiology and we limit the development of more specific treatments. ... To date, there has been general consensus that the science is not yet well enough developed to permit neuroscience-based classification. However, at some point, it is necessary to instantiate such approaches if the field is ever to reach the point where advances in genomics, pathophysiology, and behavioral science can inform diagnosis in a meaningful way.
There is no absolute timeline of when these advances might occur. Instead of providing an immediate replacement for DSM and its clinical diagnoses, RDoC is a long-term project to help the research community by defining more biologically based organizational principles for various psychopathologies:
RDoC will follow three guiding principles, all diverging from current diagnostic approaches. First, RDoC is conceived as a dimensional system (reflecting, e.g., circuit-level measurements, behavioral activity, etc.) spanning the range from normal to abnormal. ... Second, RDoC is agnostic about current disorder categories. The intent is to generate classifications stemming from basic behavioral neuroscience. Rather than starting with an illness definition and seeking its neurobiological underpinnings, RDoC begins with current understandings of behavior-brain relationships and links them to clinical phenomena. Third, RDoC will use several different levels of analysis in defining constructs for study (e.g., imaging, physiological activity, behavior, and self-reports of symptoms).
What are the biological mechanisms driving abnormalities in the observed behaviors ("constructs") of e.g. fearfulness, reward sensitivity, attention, and self-representation? As shown in the matrix below, five major domains have been proposed to group the behavioral constructs, which can be evaluated at six levels of analysis.

The basic idea is that these domains and constructs can go awry in any number of disorders. For instance, if you type "altered reward processing" into PubMed, among the 80 entries are studies in pediatric bipolar disorder, drug addiction, autism, schizophrenia, obesity, pathological gambling, mania, ADHD, and antisocial personality disorder. What are the neural correlates of altered reward processing? Is there a common mechanism across the various diagnostic categories listed above? Are many of the genes that predispose one to altered reward processing shared across disorders?

Another problem that RDoC aims to address is extensive co-morbidity in many of the current diagnostic categories. A prime example is the complex construct of borderline personality disorder (BPD), marked by affective instability, unstable interpersonal relationships, and self-destructive behavior. NIMH notes that about 85 percent of people with BPD also meet the diagnostic criteria for another disorder, including:
  • 61 percent also have at least one anxiety disorder, most commonly a specific phobia, or social phobia
  • 49 percent have an impulse-control disorder, most commonly intermittent explosive disorder
  • 38 percent have a substance abuse or dependence disorder, most commonly alcohol abuse or dependence
  • 34 percent have a mood disorder, most commonly dysthymia (mild, chronic depression), or major depression.
Here, one can view the diagnostic category of BPD as a collection of symptoms (or disorders) that can vary across individuals. The same can be said of schizophrenia. How do alterations in the underlying biological mechanisms drive various manifestations of mental disorders (Sanislow et al., 2010)?
...any given disorder can be marked by disruptions among multiple mechanisms, and one particular mechanism may contribute to the psychopathology of a large number of disorders. Thus, the same mechanisms can be implicated in “different” disorders, whereas multiple mechanisms can be implicated in “one” disorder.

Is Big Pharma abandoning psychiatry? (see Mind Hacks)

The leaders of NIMH have expressed the opinion that the DSM and ICD have hindered the development of new treatments (Insel et al., 2010). Given the limited effectiveness of many pharmaceutical interventions, it is patently obvious that a new approach is needed. Since the ultimate goal of the RDoC project is to improve treatment outcomes, its authors will have to convince some of the major drug companies to resume their "unprofitable" psychiatry R&D pipelines.

NOTE: This post is part of a blog carnival that addressed the question, "What Is Psychopathology?" {Scicurious isn't very fond of the term; neither am I...} Other contributions are listed at The Thoughtful Animal.


Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P. (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 167:748-51.

Pfeifer S. (1999). Demonic attributions in nondelusional disorders. Psychopathology 32:252-9.

Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, Wang PS, & Cuthbert BN (2010). Developing constructs for psychopathology research: Research domain criteria. Journal of abnormal psychology PMID: 20939653

NOTE: King Missile III album named after Psychopathology of Everyday Life (1901), by Sigmund Freud.

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At November 05, 2010 10:28 AM, Anonymous Anonymous said...

Perhaps they are right. If psychiatry clusters together entities that don't belong together, because it looks at the wrong features to determine similarity, then the entire enterprise could be a dead end. Not to offend anyone, but let's face it, MDs are not precisely scientific geniuses, and psychiatrists tend to be at the lower end of the MD talent distribution. Haven't we all gotten theoretically sophisticated grants trashed by clueless psychiatrists? ;)


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