Transcript Siegle 2011 Translational Research Presentation

Translational Research Updates:
Tools, toys, theories, and
trying to get funded
Greg Siegle
University of Pittsburgh
School of Medicine
Supported by MH082998
Greg Siegle is an unpaid consultant for Trial IQ and Neural Impact
Topics
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RDoC
Ambulatory EEG
One super-cool upcoming article
Automating fMRI meta-analyses
Getting translational research funded
The NIMH
Research Domain Criteria
(RDoC)
mentalhealth.gov/research-funding/rdoc
Please do:
- Look at dimensions
that span disorders –
this means recruiting
across traditional
disorder boundaries
- Consider
psychopathology as
extremes of normal
dimensions
- Integrate genetic,
neurobiological,
behavioral,
environmental, and
experiential
components
- Translate RDoC
domains to
interventions
RDoC example:
Negative Valence Systems
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Responses to acute threat (Fear).
Responses to potential harm (Anxiety)
Responses to sustained threat
Frustrative non-reward
Loss
• http://mentalhealth.gov/researchfunding/rdoc/negative-valence-systemsworkshop-proceedings.shtml
Ambulatory EEG is here!
Why care?
Targeting brain
Mechanisms
e.g., Alpha EEG (813Hz) activity
represents inactivity.
Increased LEFT frontal
alpha in depression 
assymetry
Altering
Brain-Behavior
Target:
Neurofeedback
Measuring
Brain-Behavior Target
Bargain: $299!
•
1) Train on brain target
directly. Several case
series: reduced
asymmetry & lasting
reductions in depression
and anxiety in treatmentrefractory MDD and
dysthymia patients (up to
5-year follow-up; e.g.,
Baehr, 1997)
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Davidson (2000)
American Psychologist
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Difficult to replicate
Training on failure
feedback is difficult to
tolerate
Train on emotion
template and maintain or
avoid that
Train on an emotion &
situation, test without
emotion
Must read article:
Forgeard, M. J. C., Haigh, E. A. P., Beck, A. T., Davidson, R. J., Henn, F.
A., Maier, S. F., Mayberg, H. S., Seligman, M. E. P. (in press). Beyond
depression: Towards a process-based approach to research, diagnosis,
and treatment. Clinical Psychology: Science & Practice, 18(4).
– Learned Helplessness is not dead – it’s in the lateral
habenula…
– Biological taxonomies are essential
– Convergence among psychological and neurobiological
processes
– Implications for diagnosis and treatment
• Neurobehavioral interventions
• Go to the “prefrontal doctor” or “cingulate doctor” – not a
psychiatrist or psychologist
Finding your brain targets –
automated meta-analyses at
neurosynth.org
Interpreting your brain data:
The fMRI Individual Differences
Database!
http://www.tinyurl.com/BrainIndivDbase
Everything old is new again
Hekmat H, Vanian D
(1971): Behavior
modification through covert
semantic desensitization.
J Consult Clin Psychol.
36:248-251.
Me
Myself
Powerful
strong….
Funding: NIMH mechanisms
• Basic mechanistic research
– RDoC: RFA-MH-12-100 – Dimensional Approaches to Research
Classification in Psychiatric Disorders (R01)
– RFA-HL-12-037. Mechanistic Pathways Linking Psychosocial Stress and
Behavior (R01)
• Interventions
– PAR-11-177. Translational Research for the Development of Novel
Interventions for Mental Disorders (R21/R33)
• applications to speed the translation of emerging findings on the neuroscience of
mental disorders into novel intervention approaches
• A range of non-pharmacologic treatment approaches will be accepted, including those
based on neurophysiological, cognitive, affective, and/or social neuroscience models,
basic behavioral science, and neurodevelopmental models
– PAR-09-173, Pilot Intervention and Services Research Grants (R34)
• Includes “rehabilitative efforts to reduce residual symptoms and/or enhance
functioning.”
– PA-09-075, Collaborative R34s for Pilot Studies of Innovative Treatments in
Mental Disorders (Collaborative R34)
• This FOA should be used when at least two but no more than three sites are needed to
complete the study.
– PAR-12-007. Innovative Pilot Studies of Novel Mechanism of Action
Compounds for Treating Psychiatric Disorders (U01)
Funding: Outside NIMH
• There are mechanisms
– PA-04-109, Cross-Disciplinary Translational Research
at NIH (R01)
• Institutes: NIDA (Drug Abuse), NCI (Cancer)
• Extend basic or clinical research findings to yield a
knowledge base for the development of novel, efficacious
drug abuse prevention or treatment interventions.
– PA-11-123, Translational Research to Help Older
Adults Maintain their Health and Independence in the
Community (R01)
• Institutes: NIA (Aging)
– PA-09-075, Collaborative R34s for Pilot Studies of
Innovative Treatments in Mental Disorders
(Collaborative R34)
• Institutes: NIMH, NCCAM (Complementary)
Funding: Strategies for getting past review
• Tell your reviewers that your agency wants it
– Quote the PA
– Quote the Institute Strategic plan e.g., NIMH
• Opportunities to Develop New Psychosocial and Behavioral
Therapies ■ Determine the basic mechanisms by which psychosocial
interventions operate to produce therapeutic change to increase
opportunities for innovative developments.
– Quote the branch, e.g., NIMH Division of Adult Translational
Research and Treatment Development (DATR) mission
• Define predictors and understand the mechanism of treatment
response.
• Create and refine biomarkers, behavioral assessments, and
phenotypic characterizations of disease.
• Evaluate existing therapeutics for new indications, and, in
collaboration with academic, industry, and regulatory agencies,
hasten the development of more effective new treatments for mental
illness.
Funding: Strategies for getting past review
• Rumors: ITV doesn’t like mechanism.
– Strategy: “If we don’t measure mechanism we could miss
our effects”
Change in Symptoms
Observed
Change in
Observed Intervention could be
physiological
working by predicted
or
mechanism.
neuroimaging
data during
the
intervention
Not
Mechanism isn’t
Observed targeted, but that
doesn’t matter –
mechanism isn’t key to
symptom change.
Not Observed
Intervention targeting the
mechanism but mechanism
isn’t (immediately) key to
symptom change for this
person
Intervention not working,
possibly because it’s not
targeting the mechanism. Must
revise the intervention OR the
assessment
Siegle et al (2007) Cognitive Therapy and Research
– Note: Program is speaking regularly to ITV reviewers
Funding: Strategies for getting past review
• Rumor: APDA doesn’t like intervention
– Strategy: Discuss short-term interventions as a
probe of causal relationships between brain and
symptoms
– Emphasize public health relevance of developing
the intervention
– Consider R21 mechanisms. They may indulge
cheap over expensive.
– Pilot data helps even if the app says you don’t need
pilot data
Funding: Strategies for getting past review
• Rumor: NCCAM wants us….
– “studies focusing on CAM interventions used frequently by
the American public, and on the conditions for which they
are most frequently used are particularly encouraged.”
• If we can show we’re a viable mainstream (i.e., app-downloadable)
but unconventional treatment source, we have a shot…. Talk to
program!
– Basic and Translational Research
NCCAM's support of basic research emphasizes and
encourages in vitro and in vivo studies of the biological
effects and mechanisms of action underlying
complementary and alternative medicine (CAM)
approaches, as well as studies characterizing the active
elements of an intervention,