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The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

ABSTRACT: Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) while performing the ToL task at baseline and again after 16 weeks of SSRI treatment. Internetwork connectivity was compared across the groups and treatment statuses (pretreatment versus posttreatment). At baseline, compared with the HCs, the OCD patients showed lower internetwork connectivity between the dorsal attention network and the default-mode network during the ToL planning task. After 16 weeks of SSRI treatment, the OCD patients showed improved clinical symptoms accompanied by normalized network connectivity, although their improved behavioral performance in the ToL task did not reach that of the HCs. Our findings support the conceptualization of OCD as a network disease characterized by an imbalance between brain networks during goal-directed planning and suggest that internetwork connectivity may serve as an early biomarker of the effects of SSRIs on goal-directed planning.

SUBMITTER: Kim M

PROVIDER: S-EPMC7691328 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

Kim Minah M Jung Wi Hoon WH Shim Geumsook G Kwon Jun Soo JS

Scientific reports 20201126 1

Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent func ...[more]

PMID: 33244182

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Project description:ImportanceDimensional definitions of transdiagnostic mental health problems have been suggested as an alternative to categorical diagnoses, having the advantage of capturing heterogeneity within diagnostic categories and similarity across them and bridging more naturally psychological and neural substrates.ObjectiveTo examine whether a self-reported compulsivity dimension has a stronger association with goal-directed and related higher-order cognitive deficits compared with a diagnosis of obsessive-compulsive disorder (OCD).Design, setting, and participantsIn this cross-sectional study, patients with OCD and/or generalized anxiety disorder (GAD) from across the United States completed a telephone-based diagnostic interview by a trained rater, internet-based cognitive testing, and self-reported clinical assessments from October 8, 2015, to October 1, 2017. Follow-up data were collected to test for replicability.Main outcomes and measuresPerformance was measured on a test of goal-directed planning and cognitive flexibility (Wisconsin Card Sorting Test [WCST]) and a test of abstract reasoning. Clinical variables included DSM-5 diagnosis of OCD and GAD and 3 psychiatric symptom dimensions (general distress, compulsivity, and obsessionality) derived from a factor analysis.ResultsOf 285 individuals in the analysis (mean [SD] age, 32 [12] years; age range, 18-77 years; 219 [76.8%] female), 111 had OCD; 82, GAD; and 92, OCD and GAD. A diagnosis of OCD was not associated with goal-directed performance compared with GAD at baseline (? [SE], -0.02 [0.02]; P?=?.18). In contrast, a compulsivity dimension was negatively associated with goal-directed performance (? [SE], -0.05 [0.02]; P?=?.003). Results for abstract reasoning task and WCST mirrored this pattern; the compulsivity dimension was associated with abstract reasoning (? [SE], 2.99 [0.63]; P?<?.001) and several indicators of WCST performance (eg, categories completed: ? [SE], -0.57 [0.09]; P?<?.001), whereas OCD diagnosis was not (abstract reasoning: ? [SE], 0.39 [0.66]; P?=?.56; categories completed: ? [SE], -0.09 [0.10]; P?=?.38). Other symptom dimensions relevant to OCD, obsessionality, and general distress had no reliable association with goal-directed performance, WCST, or abstract reasoning. Obsessionality had a positive association with requiring more trials to reach the first category on the WCST at baseline (? [SE], 2.92 [1.39]; P?=?.04), and general distress was associated with impaired goal-directed performance at baseline (? [SE],-0.04 [0.02]; P?=?.01). However, unlike the key results of this study, neither survived correction for multiple comparisons or was replicated at follow-up testing.Conclusions and relevanceDeficits in goal-directed planning in OCD may be more strongly associated with a compulsivity dimension than with OCD diagnosis. This result may have implications for research assessing the association between brain mechanisms and clinical manifestations and for understanding the structure of mental illness.

Project description:BackgroundAnxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis.Methods and findingsWe searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials.ConclusionsIn this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.

Project description:BackgroundA recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity.MethodsMultiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived.ResultsReduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects.ConclusionsThese data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.

Project description:Obsessive-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).To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.A 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.While 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.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.Patients 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.Adding 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.clinicaltrials.gov Identifier: NCT00389493.

Dataset Information

The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

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The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

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