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290 views27 pagesRDoC: New Mental Health Framework
The document discusses new approaches to understanding and classifying mental disorders, including the National Institute of Mental Health's Research Domain Criteria (RDoC) project. RDoC aims to classify psychopathology based on dimensions of observable behavior and neurobiology rather than symptom-based categories. It takes a dimensional approach incorporating multiple levels of analysis from genes to self-reports. The goals are to discover more homogeneous subgroups and biomarkers to support improved treatment and prevention. This represents a shift away from traditional categorical models toward understanding mental disorders as deviations in brain circuits and behaviors.
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0% found this document useful (0 votes)
290 views27 pagesRDoC: New Mental Health Framework
The document discusses new approaches to understanding and classifying mental disorders, including the National Institute of Mental Health's Research Domain Criteria (RDoC) project. RDoC aims to classify psychopathology based on dimensions of observable behavior and neurobiology rather than symptom-based categories. It takes a dimensional approach incorporating multiple levels of analysis from genes to self-reports. The goals are to discover more homogeneous subgroups and biomarkers to support improved treatment and prevention. This represents a shift away from traditional categorical models toward understanding mental disorders as deviations in brain circuits and behaviors.
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© © All Rights Reserved
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New Understandings of Mental Health
and Brain/Behavioral Disorders
National Press
Foundation
Bruce N. Cuthbert, Ph. D.
Director, RDoC Unit
National Institute of Mental Health
19 September 2016
Traditional Approaches to Mental Illness
Alienists: mental disorders as distinct from normality
Kraepelin, Bleuler: first systematic descriptions of disorder
Disease models in psychiatry:
(1) Symptoms/signs, course of illness
(2) Assume existence of complex, yet specific diseases on
the basis of symptoms/signs
Cf. Kraepelin, mental disorders as natural disease units
(natuerliche Krankheitseinheit) [Heckers, Schiz. Bull.,2008]
The current disease model is
no longer valid for research
Current systems: DSM (Diagnostic and Statistical
Manual) and ICD (International Classification of
Diseases)
Data from genetics, pathophysiology, & psychological
mechanisms do not align well with the categories
Syndrome: A condition characterized by a set of
associated symptoms (Oxford Engl. Dict.)
Excessive heterogeneity, co-morbidity
Problem: Diagnostic categories drive the entire
research system (research grants,
pathophysiology, journals, trials, regulatory)
Two major needs for reducing
the burden of mental disorders
(1) More access to the treatments that we have
(2) Better understanding of disorder mechanisms, leading to
improved treatment and prevention interventions
.
Changing perspectives on mental disorders
Marked advances in understanding:
Instead of continuing with symptom-based definitions
(1) Understanding of major brain circuits .
(2) And the behaviors that they implement (fear, reward,
memory)
Can we understand mental disorders as deviations from
normal functioning of brain systems?
The Overarching Goals of RDoC
Develop a framework for studying psychopathology based on
dimensions of observable behavior and neurobiological
measures. research.
Posit fundamental components that may span multiple disorders
(e.g., executive function, affect regulation)
Determine the full range of variation, from normal to abnormal
Integrate genetic, neurobiological, behavioral, environmental, and
experiential components
Develop reliable and valid measures of these fundamental
components for use in basic and clinical studies
Exactly what does RDoC involve?
Focused research initiative moving toward a new
classification system: study and validate trans-diagnostic,
dimensional constructs
Concept:
1) Deeper understanding of psychological & biological systems
related to mental illness
2) New biomarkers & biosignatures
3) More homogeneous groupings for
psychopathology/pathophysiology
4) new intervention development
Not a new idea but the first implementation by a funding
agency
7
(1) The RDoC Concept: Five components
Environment
Domains
Units of Analysis
Neurodevelopment
8
RDoC Matrix: Integrative Framework
(Workshops July 2010 June 2012)
[Symptoms]
Altered Stress Reactivity
Emotion regulation problems
Lack of pleasure in usual activities
Lack of energy for productive tasks
Language delays
Executive function problems
Social withdrawal
Poor relationships
Problems with arousal-modulating systems
Sleep problems
9
Dimensional Psychiatry: Shift from
(categorical) infectious disease model to
Healthy
Disease
Level of Functioning
Complex Trait Model (full distribution)
//
Level of Functioning
Mild, Moderate, Severe levels of disorder
//
Empirically-based cutpoints for (e.g.) mild,
moderate, severe levels of dysfunction
Dimensions: Continuity in autism risk genes
Robinson, & Daly, Nat. Gen., 2016
Dimensions, Heterogeneity
in Psychotic Spectrum
Only 30% of people with psychotic illness have schizophrenia (others: brief psychotic disorder, delusional
disorder, etc.)
people with this psychosis spectrum syndrome ... Display extreme heterogeneity, both within and between
people, in psychopathology, treatment response, and outcome.
van Os, BMJ, 2016
14
Framework: Always Under Construction
[Symptoms]
Altered Stress Reactivity
Emotion regulation problems
Lack of pleasure in usual activities
Lack of energy for productive tasks
Language delays
Executive function problems
Social withdrawal
Poor relationships
Problems with arousal-modulating systems
Sleep problems
15
(2) RDoC as a practical rubric
DSM/ICD = de facto requirement for research grants and
16
so, journal publications, clinical trials, regulatory approvals
DSM goal: a standard & set of criteria for research (as well
as clinical practice)
However, DSM is inadequate for current research
But: have to have *some* standards and guidelines for
evaluating research grants in psychopathology, if DSM/ICD
system is not used.
New Ways of Grouping Patients
Experimental designs require groups and/or dimensions
How are new groups/dimensions to be discovered?
Examples from:
(1) Anxiety Disorders
(2) Psychotic disorders
(None incorporate normal-to-abnormal dimension)
17
Anxiety Disorders: Transdiagnostic
dimensions of response
Lang, McTeague, & Bradley, Psychophysiology, 2016
Contemporaneous Dimensional Approaches to Diagnosis
Psychiatry will need to move from using traditional descriptive diagnoses to clinical
entities (categories and/or dimensions) that relate more closely to the underlying
workings of the brain. Craddock & Owen, Br J Psych (2010)
19
Example: BSNIP*, parsing the
schizophrenia-bipolar spectrum
* Bipolar-Schizophrenia Network on Intermediate Phenotypes
BSNIP Biotypes: (1) Cognitive
Control, (2) Sensorimotor Reactivity
Clementz, . & Tamminga, Am J Psychiatry, in press
BSNIP: Gray Matter Loss by Biotype:
Probands and Relatives
Clementz, . & Tamminga, Am J Psychiatry, in press
Toward Individualized Prevention: Early
(pre-clinical) signs of psychosis risk
Pennsylvania
Neurodevelopmental
Cohort (N = 4,642):
Gur et al., JAMA
Psychiatry, 2014
Potential consequences of the RDoC approach
(1) Clinical trials: target engagement, experimental medicine
RDoC: Enroll patients based on measurable impairment in a
specific mechanism (e.g., excessive fear, working memory
deficit, effort valuation)
Outcome measures based on change in these functions
(2) More emphasis on (quantifiable) functioning than (selfreported) symptoms
E.g., EMA and FDA approval for cognition as an indication in
depression (following the same for schizophrenia)
24
Drug hunters challenges in developing better treatments
Int J Neuropsychopharmacol. 2010 Oct;13(9):1269-84. Epub 2010 Aug 18.
On average, a marketed psychiatric drug is efficacious in approximately
half of the patients who take it. One reason for this low response rate is
the artificial grouping of heterogeneous syndromes with different
pathophysiological mechanisms into one disorder.
25
What might future diagnostic manuals look like?
RDoC goal: Inform future versions of ICD and DSM
Likely: incremental, not radical, change
(1) More specific dimensions/subgroups within DSM/ICD
categories
(2) Over time: broader syndromes?
E.g., internalizing (or, distress disorder?); externalizing (or,
behavioral regulation disorder?); psychotic spectrum
More specific and focused treatment plans based upon
detailed assessments
26
Summary: Contemporary
Directions for Mental Disorders
Transition: broad syndromes to dimensional brain-behavior
27
models that include neurodevelopment, environment
Transition: symptom management toward cure, pre-emption,
and prevention
Big data, common data elements, different sampling frames
The future: toward precision treatment and prevention for
CNS disorders, consistent with other areas of medicine
