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January 1994, Vol 51, No. 1 >
Article | January 1994

Regional Cerebral Blood Flow Measured During Symptom Provocation in Obsessive-Compulsive Disorder Using Oxygen 15—Labeled Carbon Dioxide and Positron Emission Tomography

Scott L. Rauch, MD; Michael A. Jenike, MD; Nathaniel M. Alpert, PhD; Lee Baer, PhD; Hans C. R. Breiter, MD; Cary R. Savage, PhD; Alan J. Fischman, MD, PhD
Arch Gen Psychiatry. 1994;51(1):62-70. doi:10.1001/archpsyc.1994.03950010062008
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Background:  The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD).

Methods:  The short half-life tracer oxygen 15—labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state.

Results:  Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by selfreport on OCD analogue scales (P=.002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P<.006), left anterior cingulate cortex (P<.045), and bilateral orbitofrontal cortex (P<.008); increases in the left thalamus approached but did not reach statistical significance (P=.07).

Conclusions:  These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cigulate cortex in the pathophysiology of OCD and in mediating OCD symptoms.

REFERENCES

1 +
Jenike M.  Obsessive-compulsive disorder: a question of a neurologic lesion . Compr Psychiatry . 1984;;25:298-304.
2 +
Schwartz JM, Baxter LR, Mazziotta JC, Gerner RH, Phelps ME.  The differential diagnosis of depression: relevance of positron emission tomography studies of cerebral glucose metabolism to the bipolar-unipolar dichotomy . JAMA . 1987;;258:1368-1374.
3 +
Jenike MA, Baer L, Minichiello WE, eds. Obsessive Compulsive Disorder: Theory and Management . 2nd ed. Chicago, Ill: Year Book Medical Publishers; 1990;.
4 +
Modell J, Mountz J, Curtis G, Greden J.  Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder . J Neuropsychiatry . 1989;;1:27-36.
5 +
Baxter LR, Schwartz JM, Guze BH, Bergman K, Szuba MP.  Neuroimaging in obsessive-compulsive disorder: seeking the mediating neuroanatomy . In: Jenike MA, Baer L. Minichiello WE, eds. Obsessive Compulsive Disorder: Theory and Management . 2nd ed. Chicago, Ill: Year Book Medical Publishers; 1990;:167-188.
6 +
Rauch SL, Jenike MA.  Neurobiological models of obsessive compulsive disorder . Psychosomatics . 1993;;34:20-32.
7 +
Baxter LR Jr, Phelps JM, Mazziotta JC, Guze BH, Schwartz JM.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder: a comparison with rates in unipolar depression and normal controls . Arch Gen Psychiatry . 1987;;44:211-218.
8 +
Baxter L, Schwartz J, Mazziotta J, Phelps ME, Pahl JJ, Buze BE, Fairbanks L.  Cerebral glucose metabolic rates in nondrepressed patients with obsessive-compulsive disorder . Am J Psychiatry . 1988;;145:1560-1563.
9 +
Nordahl TE, Benkelfat C, Semple W, Gross M, King AC, Cohen RM.  Cerebral glucose metabolic rates in obsessive-compulsive disorder . Neuropsychopharmacology . 1989;;2:23-28.
10 +
Swedo SE, Schapiro MB. Gady CL, Cheslow DL, Leonard HL, Kumar A, Friedland R, Rapoport SI, Rapoport JL.  Cerebral glucose metabolism in childhoodonset obsessive-compulsive disorder . Arch Gen Psychiatry . 1989;;46:518-523.
11 +
Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder: patients treated with clomipramine . Arch Gen Psychiatry . 1990;;47:840-848.
12 +
Sawle GV, Hymas NF, Lees AJ, Frackowiak RSJ.  Obsessional slowness: functional studies with positron emission tomography . Brain . 1991;;114:2191-2202.
13 +
Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, Alazraki A, Selin CE, Ferng H-K, Munford P, Phelps ME.  Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder . Arch Gen Psychiatry . 1992;;49:681-689.
14 +
Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI, Rapoport JL, Grady CL.  Cerebral glucose metabolism in childhoodonset obsessive-compulsive disorder: revisualization during pharmacotherapy . Arch Gen Psychiatry . 1992;;49:690-694.
15 +
Machlin S, Harris G, Pearslon G, Hoehn-Saric R, Jeffery P, Camargo E.  Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study . Am J Psychiatry . 1991;;148:1240-1242.
16 +
Rubin RT, Villanueva-Meyer J, Anath J, Trajmar PG, Mena I.  Regional xenon 133 cerebral blood flow and cerebral technetium Tc 99m-HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects: determination by high-resolution single-photon emission computed tomography . Arch Gen Psychiatry . 1992;;49:695-702.
17 +
Insel TR.  Toward a neuroanatomy of obsessive-compulsive disorder . Arch Gen Psychiatry . 1992;;49:739-744.
18 +
Zohar J, Insel T, Berman K, Foa E, Hill J, Weinberger D.  Anxiety and cerebral blood flow during behavioral challenge: dissociation of central from peripheral and subjective measures . Arch Gen Psychiatry . 1989;;46:505-510.
19 +
American Psychiatric Association, Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987;.
20 +
Kops ER, Herzog H, Schmid A, Holte S, Feinendegen LE.  Performance characteristics of an eight-ring whole body PET scanner . J Comput Assist Tomogr . 1990;;14:437-445.
21 +
Talairach J, Szikla Z. Atlas of Stereotactic Anatomy of the Telencephalon . Paris, France: Masson et Cie; 1967;.
22 +
Talairach J, Tournoux P. Co-Planar Stereotaxic Atlas of the Human Brain . New York, NY: Thieme Medical Publishers Inc; 1988;.
23 +
Friston K, Frith C, Liddle P, Franckowiak R.  Comparing functional (PET) images: the assessment of significant change . J Cerebral Blood Flow Metab . 1991;;11:690-699.
24 +
Baxter LR.  Neuroimaging studies of obsessive compulsive disorder . Psychiatr Clin North Am . 1992;;15:871-884.
25 +
Papez JW.  Proposed mechanism of emotion . Arch Neurol Psychiatry . 1937;;38:725-743.
26 +
Mountz J, Modell J, Wilson M, Curtis G, Lee M, Schmaltz S, Kuhl D.  Positron emission tomographic evaluation of cerebral blood flow during state anxiety in simple phobia . Arch Gen Psychiatry . 1989;;46:501.

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1 +
Jenike M.  Obsessive-compulsive disorder: a question of a neurologic lesion . Compr Psychiatry . 1984;;25:298-304.
2 +
Schwartz JM, Baxter LR, Mazziotta JC, Gerner RH, Phelps ME.  The differential diagnosis of depression: relevance of positron emission tomography studies of cerebral glucose metabolism to the bipolar-unipolar dichotomy . JAMA . 1987;;258:1368-1374.
3 +
Jenike MA, Baer L, Minichiello WE, eds. Obsessive Compulsive Disorder: Theory and Management . 2nd ed. Chicago, Ill: Year Book Medical Publishers; 1990;.
4 +
Modell J, Mountz J, Curtis G, Greden J.  Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder . J Neuropsychiatry . 1989;;1:27-36.
5 +
Baxter LR, Schwartz JM, Guze BH, Bergman K, Szuba MP.  Neuroimaging in obsessive-compulsive disorder: seeking the mediating neuroanatomy . In: Jenike MA, Baer L. Minichiello WE, eds. Obsessive Compulsive Disorder: Theory and Management . 2nd ed. Chicago, Ill: Year Book Medical Publishers; 1990;:167-188.
6 +
Rauch SL, Jenike MA.  Neurobiological models of obsessive compulsive disorder . Psychosomatics . 1993;;34:20-32.
7 +
Baxter LR Jr, Phelps JM, Mazziotta JC, Guze BH, Schwartz JM.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder: a comparison with rates in unipolar depression and normal controls . Arch Gen Psychiatry . 1987;;44:211-218.
8 +
Baxter L, Schwartz J, Mazziotta J, Phelps ME, Pahl JJ, Buze BE, Fairbanks L.  Cerebral glucose metabolic rates in nondrepressed patients with obsessive-compulsive disorder . Am J Psychiatry . 1988;;145:1560-1563.
9 +
Nordahl TE, Benkelfat C, Semple W, Gross M, King AC, Cohen RM.  Cerebral glucose metabolic rates in obsessive-compulsive disorder . Neuropsychopharmacology . 1989;;2:23-28.
10 +
Swedo SE, Schapiro MB. Gady CL, Cheslow DL, Leonard HL, Kumar A, Friedland R, Rapoport SI, Rapoport JL.  Cerebral glucose metabolism in childhoodonset obsessive-compulsive disorder . Arch Gen Psychiatry . 1989;;46:518-523.
11 +
Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder: patients treated with clomipramine . Arch Gen Psychiatry . 1990;;47:840-848.
12 +
Sawle GV, Hymas NF, Lees AJ, Frackowiak RSJ.  Obsessional slowness: functional studies with positron emission tomography . Brain . 1991;;114:2191-2202.
13 +
Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, Alazraki A, Selin CE, Ferng H-K, Munford P, Phelps ME.  Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder . Arch Gen Psychiatry . 1992;;49:681-689.
14 +
Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI, Rapoport JL, Grady CL.  Cerebral glucose metabolism in childhoodonset obsessive-compulsive disorder: revisualization during pharmacotherapy . Arch Gen Psychiatry . 1992;;49:690-694.
15 +
Machlin S, Harris G, Pearslon G, Hoehn-Saric R, Jeffery P, Camargo E.  Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study . Am J Psychiatry . 1991;;148:1240-1242.
16 +
Rubin RT, Villanueva-Meyer J, Anath J, Trajmar PG, Mena I.  Regional xenon 133 cerebral blood flow and cerebral technetium Tc 99m-HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects: determination by high-resolution single-photon emission computed tomography . Arch Gen Psychiatry . 1992;;49:695-702.
17 +
Insel TR.  Toward a neuroanatomy of obsessive-compulsive disorder . Arch Gen Psychiatry . 1992;;49:739-744.
18 +
Zohar J, Insel T, Berman K, Foa E, Hill J, Weinberger D.  Anxiety and cerebral blood flow during behavioral challenge: dissociation of central from peripheral and subjective measures . Arch Gen Psychiatry . 1989;;46:505-510.
19 +
American Psychiatric Association, Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987;.
20 +
Kops ER, Herzog H, Schmid A, Holte S, Feinendegen LE.  Performance characteristics of an eight-ring whole body PET scanner . J Comput Assist Tomogr . 1990;;14:437-445.
21 +
Talairach J, Szikla Z. Atlas of Stereotactic Anatomy of the Telencephalon . Paris, France: Masson et Cie; 1967;.
22 +
Talairach J, Tournoux P. Co-Planar Stereotaxic Atlas of the Human Brain . New York, NY: Thieme Medical Publishers Inc; 1988;.
23 +
Friston K, Frith C, Liddle P, Franckowiak R.  Comparing functional (PET) images: the assessment of significant change . J Cerebral Blood Flow Metab . 1991;;11:690-699.
24 +
Baxter LR.  Neuroimaging studies of obsessive compulsive disorder . Psychiatr Clin North Am . 1992;;15:871-884.
25 +
Papez JW.  Proposed mechanism of emotion . Arch Neurol Psychiatry . 1937;;38:725-743.
26 +
Mountz J, Modell J, Wilson M, Curtis G, Lee M, Schmaltz S, Kuhl D.  Positron emission tomographic evaluation of cerebral blood flow during state anxiety in simple phobia . Arch Gen Psychiatry . 1989;;46:501.

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