Impact of treatment on resting cerebral blood flow and metabolism in obsessive compulsive disorder: a meta-analysis

A L van der Straten, D Denys, G A van Wingen, A L van der Straten, D Denys, G A van Wingen

Abstract

Neurobiological models of obsessive-compulsive disorder (OCD) posit that its clinical symptoms such as repetitive thoughts and behaviors are related to hyperactivity in the cortico-striato-thalamo-cortical (CSTC) circuit. Small scale neuroimaging studies have shown that treatment of OCD is associated with reduced activity across different brain structures within this circuitry. We performed the first meta-analysis of positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies that investigated cerebral blood flow or glucose metabolism in patients with OCD before and after pharmacological or psychological treatment. We calculated standardized mean differences for the regions-of-interest most often reported. The meta-analysis revealed small reductions in activity in the caudate nucleus and orbitofrontal cortex after treatment with a serotonin reuptake inhibitor or cognitive behavioral therapy. Small reductions were also observed in the thalamus when one SPECT study with a large opposite effect was excluded from the analysis. Meta-regression analyses for the caudate nucleus showed no significant effect of the type of treatment, decrease in symptom severity, mean duration until the follow-up scan, or year of publication. These results show that pharmacological and psychological treatments reduce resting CSTC circuit activity, and provide further support for the CSTC circuit model in OCD.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Forest plot of effect sizes of the caudate nucleus for PET and SPECT studies combined.
Figure 3
Figure 3
Forest plot of effect sizes of the orbitofrontal cortex for PET and SPECT studies combined.
Figure 4
Figure 4
Forest plot of effect sizes of the thalamus for PET and SPECT studies combined.

References

    1. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53–63. doi: 10.1038/mp.2008.94.
    1. Koran LM, et al. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164:5–53.
    1. Goodman WK, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989;46:1012–1016. doi: 10.1001/archpsyc.1989.01810110054008.
    1. van den Heuvel, O. A. et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol, 10.1016/j.euroneuro.2015.12.005 (2015).
    1. Benkelfat C, et al. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry. 1990;47:840–848. doi: 10.1001/archpsyc.1990.01810210048007.
    1. Baxter, L. R. Jr. et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry49, 681–9 (1992).
    1. Schwartz JM, et al. Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry. 1996;53:109–113. doi: 10.1001/archpsyc.1996.01830020023004.
    1. Saxena S, et al. Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder. Neuropsychopharmacology. 1999;21:683–693. doi: 10.1016/S0893-133X(99)00082-2.
    1. Hansen ES, Hasselbalch S, Law I, Bolwig TG. The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study. Int J Neuropsychopharmacol. 2002;5:1–10. doi: 10.1017/S1461145701002681.
    1. Swedo SE, et al. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy. Arch Gen Psychiatry. 1992;49:690–694. doi: 10.1001/archpsyc.1992.01820090018003.
    1. Perani D, et al. [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. The British journal of psychiatry: the journal of mental science. 1995;166:244–250. doi: 10.1192/bjp.166.2.244.
    1. Saxena S, et al. Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression. Arch Gen Psychiatry. 2002;59:250–261. doi: 10.1001/archpsyc.59.3.250.
    1. Apostolova I, et al. Effects of behavioral therapy or pharmacotherapy on brain glucose metabolism in subjects with obsessive-compulsive disorder as assessed by brain FDG PET. Psychiatry Res. 2010;184:105–116. doi: 10.1016/j.pscychresns.2010.08.012.
    1. Yamanishi T, et al. Changes after behavior therapy among responsive and nonresponsive patients with obsessive-compulsive disorder. Psychiatry Res. 2009;172:242–250. doi: 10.1016/j.pscychresns.2008.07.004.
    1. Nakatani E, et al. Effects of behavior therapy on regional cerebral blood flow in obsessive-compulsive disorder. Psychiatry Res. 2003;124:113–120. doi: 10.1016/S0925-4927(03)00069-6.
    1. Ho Pian KL, et al. Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine. Psychiatry Res. 2005;138:89–97. doi: 10.1016/j.pscychresns.2004.12.003.
    1. Hoehn-Saric R, Pearlson GD, Harris GJ, Machlin SR, Camargo EE. Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. Am J Psychiatry. 1991;148:1243–1245. doi: 10.1176/ajp.148.9.1243.
    1. Rubin RT, Ananth J, Villanueva-Meyer J, Trajmar PG, Mena I. Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment. Biol Psychiatry. 1995;38:429–437. doi: 10.1016/0006-3223(94)00305-M.
    1. Diler RS, Kibar M, Avci A. Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder. Yonsei Med J. 2004;45:90–99. doi: 10.3349/ymj.2004.45.1.90.
    1. Karadag F, et al. The comparison of pre- and post-treatment (99m)Tc HMPAO brain SPECT images in patients with obsessive-compulsive disorder. Psychiatry Res. 2013;213:169–177. doi: 10.1016/j.pscychresns.2012.07.005.
    1. Valentine J. How Many Studies Do You Need? A Primer on Statistical Power for Meta-Analysis. Journal of Educational and Behavioral Statistics. 2010;35:215–247. doi: 10.3102/1076998609346961.
    1. Borenstein, M., Hedges, L., Higgins, J. & Rothstein, H. Comprehensive meta-analysis version 2. Engelwood, NJ: Bistate (2005).
    1. Hedges, L. V. & Olkin, I. Statistical methods for meta-analysis (Academic Press, 1985).
    1. Cohen, J. Statistical Power Analysis for the Behavioral Sciences (Routledge Academic, 1988).
    1. Holm S. A Simple Sequentially Rejective Multiple Test Procedure. Scandinavian Journal of Statistics. 1979;6:65–70.
    1. Deutsch G, Mountz JM, Katholi CR, Liu HG, Harrell LE. Regional stability of cerebral blood flow measured by repeated technetium-99m-HMPAO SPECT: implications for the study of state-dependent change. J Nucl Med. 1997;38:6–13.
    1. Holcomb HH, et al. PET-FDG test-retest reliability during a visual discrimination task in schizophrenia. J Comput Assist Tomogr. 1993;17:704–709. doi: 10.1097/00004728-199309000-00007.
    1. Bartlett EJ, et al. Reproducibility of cerebral glucose metabolic measurements in resting human subjects. J Cereb Blood Flow Metab. 1988;8:502–512. doi: 10.1038/jcbfm.1988.91.
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560. doi: 10.1136/bmj.327.7414.557.
    1. Aylward EH, et al. Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging. Arch Gen Psychiat. 1996;53:577–584. doi: 10.1001/archpsyc.1996.01830070021006.
    1. Whiteside SP, Port JD, Abramowitz JS. A meta-analysis of functional neuroimaging in obsessive-compulsive disorder. Psychiat Res-Neuroim. 2004;132:69–79. doi: 10.1016/j.pscychresns.2004.07.001.
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634. doi: 10.1136/bmj.315.7109.629.
    1. Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med. 1995;14:395–411. doi: 10.1002/sim.4780140406.
    1. Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med. 2002;21:1559–1573. doi: 10.1002/sim.1187.
    1. Kang DH, et al. Brain glucose metabolic changes associated with neuropsychological improvements after 4 months of treatment in patients with obsessive-compulsive disorder. Acta Psychiatr Scand. 2003;107:291–297. doi: 10.1034/j.1600-0447.2003.00070.x.
    1. Hendler T, et al. Brain reactivity to specific symptom provocation indicates prospective therapeutic outcome in OCD. Psychiatry Res. 2003;124:87–103. doi: 10.1016/S0925-4927(03)00091-X.
    1. Carey PD, et al. Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry. 2004;4:30. doi: 10.1186/1471-244X-4-30.
    1. Molina V, et al. Drug therapy and cerebral perfusion in obsessive-compulsive disorder. J Nucl Med. 1995;36:2234–2238.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. doi: 10.1371/journal.pmed.1000097.
    1. Saxena S, et al. Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder. Mol Psychiatry. 2009;14:197–205. doi: 10.1038/sj.mp.4002134.
    1. Thorsen AL, van den Heuvel OA, Hansen B, Kvale G. Neuroimaging of psychotherapy for obsessive-compulsive disorder: A systematic review. Psychiatry Res. 2015;233:306–313. doi: 10.1016/j.pscychresns.2015.05.004.
    1. Aouizerate B, et al. Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology. Prog Neurobiol. 2004;72:195–221. doi: 10.1016/j.pneurobio.2004.02.004.
    1. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410–424. doi: 10.1038/nrn3746.
    1. Ginsberg MD, et al. Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task. Ann Neurol. 1988;23:152–160. doi: 10.1002/ana.410230208.
    1. Conca A, et al. Preliminary findings of simultaneous 18F-FDG and 99mTc-HMPAO SPECT in patients with depressive disorders at rest: differential correlates with ratings of anxiety. Psychiatry Res. 2000;98:43–54. doi: 10.1016/S0925-4927(99)00051-7.
    1. Dunn RT, et al. Preliminary findings of uncoupling of flow and metabolism in unipolar compared with bipolar affective illness and normal controls. Psychiatry Res. 2005;140:181–198. doi: 10.1016/j.pscychresns.2005.07.005.

Source: PubMed

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