Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: A PET symptom provocation study

Harvard University, Cambridge, Massachusetts, United States
Neuropsychopharmacology (Impact Factor: 7.05). 12/2002; 27(5):782-91. DOI: 10.1016/S0893-133X(02)00351-2
Source: PubMed


The purpose of this study was to identify neuroimaging predictors of medication response in contamination-related obsessive compulsive disorder (OCD). Prior studies of OCD had indicated that glucose metabolic rates within orbitofrontal cortex (OFC) were inversely correlated with subsequent response to serotonergic reuptake inhibitors (SRIs) and that glucose metabolic rates within posterior cingulate cortex (PCC) were positively correlated with subsequent response to cingulotomy. Nine subjects with contamination-related OCD underwent a 12-week open trial of treatment with the SRI fluvoxamine. Percent change in Yale-Brown Obsessive Compulsive Scale score, from pre- to post-treatment, served as the index of treatment response. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) were obtained prior to treatment, in the context of a symptom provocation paradigm. Statistical parametric mapping was used to identify brain loci where pre-treatment rCBF was significantly correlated with subsequent treatment response. Consistent with a priori hypotheses, lower rCBF values in OFC and higher rCBF values in PCC predicted better treatment response. This same pattern of associations was present regardless of whether the imaging data were acquired during a provoked or neutral state. These findings are consistent with prior studies of OCD, indicating that PET indices of brain activity within OFC are inversely correlated with subsequent response to SRIs. In addition, similar to findings regarding cingulotomy for OCD, indices of activity within PCC appear to be positively correlated with response to fluvoxamine as well. Finally, this pattern is sufficiently robust as to be relatively independent of symptomatic state at the time of tracer uptake.

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Available from: Darin D Dougherty, Mar 24, 2014
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    • "Another important line of research has focused on the identification of neural biomarkers that may predict pharmacological treatment outcomes. For example , resting-state positron emission tomography (PET) studies have found that decreased pre-treatment regional cerebral blood flow (rCBF) in the orbitofrontal cortex is associated with a better response to serotonin reuptake inhibitors (Swedo et al. 1992; Brody et al. 1998; Saxena et al. 1999; Rauch et al. 2002). Studies have also found that increased rCBF in the posterior cingulate gyrus correlates with clinical improvement after treatment with cingulotomy and fluvoxamine (Rauch et al. 2001, 2002). "
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    ABSTRACT: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.
    Psychological Medicine 11/2013; 44(10):1-13. DOI:10.1017/S0033291713002766 · 5.94 Impact Factor
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    • "In contrast, Rauch and colleagues [36] found that state of the participants did not affect the prediction of response to fluvoxamine in OCD. In a PET study, these authors found that pre-treatment regional cerebral blood flow (rCBF) measured in neutral and symptomatic states similarly predicted treatment response: lower pre-treatment rCBF in orbitofrontal cortex and greater pre-treatment rCBF in the posterior cingulate cortex predicted better response to fluvoxamine. "
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    ABSTRACT: Although several psychological and pharmacological treatment options are available for anxiety disorders, not all patients respond well to each option. Furthermore, given the relatively long duration of adequate treatment trials, finding a good treatment fit can take many months or longer. Thus, both clinicians and patients would benefit from the identification of objective pre-treatment measures that predict which patients will best respond to a given treatment. Recent studies have begun to use biological measures to help predict symptomatic change after treatment in anxiety disorders. In this review, we summarize studies that have used structural and functional neuroimaging measures to predict treatment response in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). We note the limitations of the current studies and offer suggestions for future research. Although the literature is currently small, we conclude that pre-treatment neuroimaging measures do appear to predict treatment response in anxiety disorders, and future research will be needed to determine the relative predictive power of neuroimaging measures as compared to clinical and demographic measures.
    Biology of Mood and Anxiety Disorders 08/2013; 3(1):15. DOI:10.1186/2045-5380-3-15
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    • "The authors proposed that the response to SSRIs may be related to the short-term plasticity of cortical neurons. However, Rauch [21] used SPM methods to investigate predictors of the response to fluvoxamine treatment with contamination-related OCD patients in a PET study in the context of a symptom-provocation paradigm. This study reported that decreased rCBF values in the OFC and increased rCBF values in the posterior cingulate cortex predicted a better response to treatment. "
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    ABSTRACT: Objective To analyze the correlation between the pharmacotherapy response and the characteristics of the pre-treatment regional cerebral blood flow (rCBF) in patients with obsessive-compulsive disorder (OCD). Methods Single-photon emission-computed tomography (SPECT) was used to determine the pre-treatment rCBF in 30 OCD patients and 30 normal controls. Based on their clinical remission response, the subjects were divided into two groups: selective serotonin reuptake inhibitors (SSRIs) and SSRIs plus quetiapine. The subjects with clinical remission response were identified after treatment for a period of 24 weeks, and the rCBF imaging data were processed using statistical parametric mapping (SPM) software with two-sample Z-tests. Results Nineteen OCD patients who achieved clinical remission were included in the study. Increased rCBF in forebrain regions, including the frontal lobe, cingulate gyrus, hypothalamus, and basal ganglia, was found in 11 responders to SSRIs compared to normal control patients. The eight SSRI plus quetiapine responders exhibited a decrease in rCBF within posterior brain regions, including the parietal lobe, cerebellar vermis, and occipital lobe, and an increase in rCBF in the frontal lobe, thalamus, basal ganglia, and cerebellum tonsil compared to normal control patients. Conclusions The characteristics of increased rCBF in forebrain regions and decreased rCBF in posterior brain regions before treatment of OCD patients was a potentially predictor of treatment response to guide treatment options.
    Behavioral and Brain Functions 07/2013; 9(1):31. DOI:10.1186/1744-9081-9-31 · 1.97 Impact Factor
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