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

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.