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Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline.

ABSTRACT: Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the ?-[11C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Sixteen medication-free OCD patients were randomly assigned to 12 weeks of either CBT or sertraline treatment. Pre-to-post treatment changes in the ?-[11C]methyl-L-tryptophan brain trapping constant, K* (ml/g/min), were assessed as a function of symptom response, and correlations with symptom improvement were examined. Responders/partial responders to treatment did not show significant changes in relative regional tracer uptake; rather, in responders/partial responders, 12 weeks of treatment led to serotonin synthesis capacity increases that were brain-wide. Irrespective of treatment modality, baseline serotonin synthesis capacity in the raphe nuclei correlated positively with clinical improvement. These observations suggest that, for some patients, successful remediation of OCD symptoms might be associated with greater serotonergic tone.

SUBMITTER: Lissemore JI

PROVIDER: S-EPMC5904107 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline.

Lissemore Jennifer I JI Sookman Debbie D Gravel Paul P Berney Alexandre A Barsoum Amir A Diksic Mirko M Nordahl Thomas E TE Pinard Gilbert G Sibon Igor I Cottraux Jean J Leyton Marco M Benkelfat Chawki C

Translational psychiatry 20180418 1

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective treatments for some patients with obsessive-compulsive disorder (OCD), yet little is known about the neurochemical changes related to these treatment modalities. Here, we used positron emission tomography and the α-[<sup>11</sup>C]methyl-L-tryptophan tracer to examine the changes in brain regional serotonin synthesis capacity in OCD patients following treatment with CBT or SSRI treatment. Si ...[more]

PMID: 29666372

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Project description:ImportanceObsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).ObjectiveTo compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.Design, setting, and participantsA randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.InterventionsWhile continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.Main outcome and measureThe Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.ResultsPatients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.Conclusions and relevanceAdding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.Trial registrationclinicaltrials.gov Identifier: NCT00389493.

Project description:IntroductionObsessive-compulsive disorder (OCD) is characterized by recurrent distressing thoughts and repetitive behaviors, or mental rituals performed to reduce anxiety. Recent neurobiological techniques have been particularly convincing in suggesting that cortico-striatal-thalamic-cortico (CSTC) circuits, including orbitofrontal cortex (OFC) and striatum regions (caudate nucleus and putamen), are responsible for mediation of OCD symptoms. However, it is still unclear how these regions are affected by OCD treatments in adult patients. To address this yet open question, we conducted a systematic review of all studies examining neurobiological changes before and after first-line psychological OCD treatment, i.e., cognitive-behavioral therapy (CBT).MethodsStudies were included if they were conducted in adults with OCD and they assessed the neurobiological effects of CBT before and after treatment. Two databases were searched: PsycINFO and PubMed for the time frame up to May 2022.ResultsWe obtained 26 pre-post CBT treatment studies performed using different neurobiological techniques, namely functional magnetic resonance imaging (fMRI), Positron emission tomography (PET), regional cerebral blood flow (rCBF), 5-HT concentration, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), Electroencephalography (EEG). Neurobiological data show the following after CBT intervention: (i) reduced activations in OFC across fMRI, EEG, and rCBF; (ii) decreased activity in striatum regions across fMRI, rCBF, PET, and MRI; (iii) increased activations in cerebellum (CER) across fMRI and MRI; (iv) enhanced neurochemical concentrations in MRS studies in OFC, anterior cingulate cortex (ACC) and striatum regions. Most of these neurobiological changes are also accompanied by an improvement in symptom severity as assessed by a reduction in the Y-BOCS scores.ConclusionCognitive-behavioral therapy seems to be able to restructure, modify, and transform the neurobiological component of OCD, in addition to the clinical symptoms. Nevertheless, further studies are necessary to frame the OCD spectrum in a dimensional way.

Project description:BackgroundCognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD.MethodsTwenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix.ResultsThinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness.ConclusionsThe current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.

Dataset Information

Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline.

Publications

Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline.

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