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An Examination of Rostral Anterior Cingulate Cortex
Function and Neurochemistry in OCD
Brian P. Brennan, MD, MMSc
Director of Medical Research, OCDI, McLean Hospital
Assistant Professor of Psychiatry, Harvard Medical School
Disclosures
Research funding from Eli Lilly and Transcept
Pharmaceuticals
Free study medication from Sanofi
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OCD: Neurochemistry
It’s not just about serotonin…
Only about half of OCD patients respond to
treatment with serotonin-reuptake inhibitor (SRI)
Mean improvement in symptoms with SRI is only
20-40%
Majority of OCD patients require additional
behavioral or pharmacologic treatment
Jenike, NEJM 2004
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OCD: Glutamate
Abnormal brain glutamate levels in OCD patients
Association between OCD and glutamate-related
genes (e.g., SLC1A1, DLGAP1, GRIN2B,
GRIK2)
Gene knockout animal models of OCD (e.g.,
SAPAP3, Slitrk5, SLC1A1)
Preliminary evidence that glutamate-modulating
medications reduce OCD symptoms (e.g.,
memantine, riluzole, N-acetylcysteine, ketamine)
Pittenger et al., Pharmacol Ther 2012
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Proton Magnetic Resonance
Spectroscopy (1H-MRS)
Glx = Glutamate +
Glutamine
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Glutamatergic Synapse
Pittenger et al., Pharmacol Ther 2012
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OCD: Glutamate/MRS
Moore et al., J Am Acad Child Adolesc Psychiatry 1998
Rosenberg et al., J Am Acad Child Adolesc Psychiatry 2000
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Conflicting 1H-MRS Findings in OCD
Brennan et al., Biol Psychiatry 2013
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2D J-resolved 1H-MRS
Brennan et al., Neuropsychopharmacology 2015
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Emotional Counting Stroop Task
Bush et al., Trends Cogn Sci 2000
Brennan et al., Neuropsychopharmacology 2015
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Results: fMRI
Brennan et al., Neuropsychopharmacology 2015
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Results: 1H-MRS
Brennan et al., Neuropsychopharmacology 2015
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1H-MRS
and OCD: Future Directions
Why are 1H-MRS studies of OCD inconclusive:
Samples too small
Samples too heterogeneous (e.g., comorbidity, meds)
Suboptimal MRS methods (e.g., low field strength, primarily
examining Glx)
Only present in pediatric-onset OCD or early in course of
illness?
Only present in genetically-distinct subpopulations?
Impact on related neurotransmitter systems (e.g., GABA)?
Can animal models provide insights?
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Thank You!
Office of Clinical Assessment and Research, OCDI, McLean
Hospital
Michael Jenike
Darin Dougherty
Diane Davey
Jason Elias
Jesse Crosby
Jason Krompinger
Brittany Mathes
Biological Psychiatry Laboratory, McLean Hospital
Harrison Pope, Jr.
James Hudson
Erin Ryan
Chris Perriello
Alison Athey (now at Case Western)
Center for Depression, Anxiety, and Stress Research, McLean
Hospital
Scott Rauch
Scott Killgore (now at U. of Arizona)
Olga Tkachenko (now at U. of Penn)
Zachary Schwab (now at U. of Kansas)
McLean Imaging Center
Eric Jensen
Schizophrenia and Bipolar Disorder Research Program,
McLean Hospital
Justin Baker
Richard Juelich
Funding Support:
NIMH K23-MH092397
NARSAD
Sidney R. Baer, Jr. Foundation
The David Judah Fund
Private Donors
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