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Relevance of orbitofrontal neurochemistry for the outcome of cognitive-behavioural therapy in patients with obsessive–compulsive disorder

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Abstract

Since the advent of non-invasive methods such as proton magnetic resonance spectroscopy (1H-MRS), obsessive–compulsive disorder (OCD) has been increasingly associated with an altered composition of neurometabolites and neurotransmitters in several brain areas. Particularly, Inositol has not only been implicated in OCD pathophysiology, but also shown effective in pilot studies in therapy-refractory OCD patients. However, the relevance of regional brain neurochemistry for therapy outcome has not yet been investigated. Whereas numerous neuroimaging findings support a dysfunction of the orbitofrontal cortex (OFC) in OCD, MR-spectroscopic investigations of this region are missing. 1H-MRS and psychometric measurements were obtained from twenty unmedicated patients with OCD, subsequently enrolled in a 3-month structured inpatient cognitive-behavioural therapy programme, and from eleven matched control subjects. Multiple regression of symptom score changes (Y-BOCS) on (myo-)inositol concentrations in three areas (right orbitofrontal cortex (OFC), right striatum and anterior cingulate cortex) was performed. The concentration of (myo-)inositol in the OFC only predicted the outcome of subsequent CBT regarding Y-BOCS score reduction (Spearman’s r s  = .81, P < 0.003, corrected). The (myo-)inositol concentration did not differ between OCD patients and healthy controls and did not change during therapy. We provide preliminary evidence for a neurochemical marker that may prove informative about a patient’s future benefit from behaviour therapy. Inositol, a metabolite involved in cellular signal transduction and a spectroscopic marker of glial activity, predicted the response to CBT selectively in the OFC, adding to the evidence for OFC involvement in OCD and highlighting neurobiological underpinnings of psychotherapy.

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Acknowledgments

This research was supported by the Deutsche Forschungsgemeinschaft (DFG, Grants BR 1766/4-2 and VO 542/1-2). We thank Jane Klemen and Eszter Schoell for helpful comments.

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The authors declare that they have no conflict of interest.

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Correspondence to Bartosz Zurowski.

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Bartosz Zurowski and Andreas Kordon equally contributed to this work.

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406_2012_304_MOESM1_ESM.jpg

Supplemental Fig. S1 Voxel position in the right orbitofrontal cortex (OFC) of a sample OCD patient is shown on a sagittal T1-weighted MR slice. Insert a (blue) depicts the transversal plane. Insert b (green) depicts the coronal plane. Red lines in both inserts correspond to the sagittal slice in the main figure (radiological convention; L=R). Landmark-oriented voxel positioning was performed according to a pre-defined and evaluated standard allowing for exact and reproducible positioning. (JPEG 476 kb)

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Zurowski, B., Kordon, A., Weber-Fahr, W. et al. Relevance of orbitofrontal neurochemistry for the outcome of cognitive-behavioural therapy in patients with obsessive–compulsive disorder. Eur Arch Psychiatry Clin Neurosci 262, 617–624 (2012). https://doi.org/10.1007/s00406-012-0304-0

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