FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder

Abstract

In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [¹⁸F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale–Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F=6.07, d.f.=1,17, P=0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (τ=0.35, P=0.04), but worse outcome (τ=−0.57, P=0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.

Introduction

Functional brain imaging studies have implicated frontal–subcortical brain circuitry in the mediation of obsessive-compulsive disorder (OCD). Specifically, [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) studies have shown hypermetabolism in the orbitofrontal cortex (OFC) (Baxter et al., 1987, Baxter et al., 1988, Nordahl et al., 1989, Swedo et al., 1989, Sawle et al., 1991), anterior cingulate gyrus (AC) (Swedo et al., 1989, Perani et al., 1995) and head of the caudate nucleus (Cd) (Baxter et al., 1987, Baxter et al., 1988, Benkelfat et al., 1990) in subjects with OCD compared with normal control subjects. When subjects with OCD are successfully treated with medication, metabolism in the OFC (Benkelfat et al., 1990, Swedo et al., 1992), AC (Swedo et al., 1992, Perani et al., 1995), and Cd (Benkelfat et al., 1990, Baxter et al., 1992) has been found to decrease significantly. In addition, patients treated successfully with behavior therapy (BT) have also shown decreases in Cd metabolism (Baxter et al., 1992Schwartz et al., 1996).

Functional imaging data have also been used to determine associations between pre-treatment regional brain metabolism and eventual treatment response. Swedo et al. (1989)found that responders to 2 months of clomipramine had lower pre-treatment absolute rates of metabolism in the right OFC and right AC than did non-responders. However, no one has yet reported pre-treatment PET predictors of treatment response to BT. Therefore we undertook an analysis to determine if pre-treatment glucose metabolic activity in regions previously associated with OCD symptomatology would predict response to BT. We also sought to determine whether pre-treatment regional brain metabolism in a small group of fluoxetine-treated subjects was associated with treatment response in a similar way to the findings of Swedo et al. (1989).