Treatment Response In Obsessive-compulsive Disorder Research Articles

Effectiveness of One Videoconference-Based Exposure and Response Prevention Session at Home in Adjunction to Inpatient Treatment in Persons With Obsessive-Compulsive Disorder: Nonrandomized Study.

Therapist-guided exposure and response prevention (ERP) for the treatment of obsessive-compulsive disorder (OCD) is frequently conducted within clinical settings but rarely at places where patients are usually confronted with OCD symptom-provoking situations in daily life (eg, at home). This study aimed to investigate patients' views on 1 ERP session at home via videoconference and its impact on treatment outcome. A total of 64 inpatients with OCD received 1 session of therapist-guided videoconference-based ERP at home in adjunction to a multimodal inpatient treatment between 2015 and 2020. Compared with 64 age- and sex-matched controls who received a multimodal inpatient treatment without 1 session of videoconference-based ERP at home, patients who received 1 session of videoconference-based ERP in adjunction to a multimodal inpatient treatment showed stronger reductions in OCD symptom severity from admission to discharge. Before the videoconference-based ERP session, patients reported high rationale credibility and treatment expectancy. After the videoconference-based ERP session, patients reported medium-to-high positive mood as well as depth and smoothness of the session, and they perceived the working alliance as high. Results highlight the importance of administering therapist-guided ERP sessions in patients' natural environment to enhance treatment response in OCD. Videoconference-based ERP as add-on to treatment as usual is, therefore, a promising approach to facilitate the application of ERP in patients' natural environment and foster the generalization of ERP conducted in clinical settings.

Hyperconnecitivity between dorsal attention and frontoparietal networks predicts treatment response in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) presented with repetitive obsessions and/or compulsions were associated with disrupted resting-state functional connectivity (rs-FC). To investigate the pharmacological treatment effect on rs-FC changes in OCD patients we conducted the seed-to-voxel FC analyses using dorsal attention network (DAN), default mode network (DMN), salience network (SN) and frontoparietal network (FPN) and basal ganglia seeds. Twenty-two healthy subjects and twenty-four unmedicated OCD patients underwent resting-state functional magnetic resonance imaging. Patients were rescanned after 12 weeks of escitalopram treatment. We found increased FC both within the DAN and between the DAN and the FPN which was ameliorated after medication and correlated significantly with the clinical improvement in obsession scores. We also observed an anticorrelation between the left caudate and the supplementary motor area in unmedicated OCD patients which also normalized with treatment. Results further showed treatment related normalization of orbitofrontal cortex hyperconnectivity with DMN and hypoconnectivity with DAN whereas aberrant FC between the SN and visual areas appears to be a medication effect. We suggest that DAN to FPN hyperconnectivity which is positively correlated with clinical improvement in obsession scores at pre-treatment stage in present study has a potential for being a neuroimaging marker to predict the treatment response in OCD.

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response.

Obsessive-compulsive disorder (OCD) is a prevalent mental disorder affecting ~2-3% of the population. This disorder involves genetic and, possibly, epigenetic risk factors. The dynamic nature of epigenetics also presents a promising avenue for identifying biomarkers associated with symptom severity, clinical progression, and treatment response in OCD. We, therefore, conducted a comprehensive case-control investigation using Illumina MethylationEPIC BeadChip, encompassing 185 OCD patients and 199 controls recruited from two distinct sites in Germany. Rigorous clinical assessments were performed by trained raters employing the Structured Clinical Interview for DSM-IV (SCID-I). We performed a robust two-step epigenome-wide association study that led to the identification of 305 differentially methylated CpG positions. Next, we validated these findings by pinpointing the optimal set of CpGs that could effectively classify individuals into their respective groups. This approach identified a subset comprising 12 CpGs that overlapped with the 305 CpGs identified in our EWAS. These 12 CpGs are close to or in genes associated with the sweet-compulsive brain hypothesis which proposes that aberrant dopaminergic transmission in the striatum may impair insulin signaling sensitivity among OCD patients. We replicated three of the 12 CpGs signals from a recent independent study conducted on the Han Chinese population, underscoring also the cross-cultural relevance of our findings. In conclusion, our study further supports the involvement of epigenetic mechanisms in the pathogenesis of OCD. By elucidating the underlying molecular alterations associated with OCD, our study contributes to advancing our understanding of this complex disorder and may ultimately improve clinical outcomes for affected individuals.

Response inhibition in youth undergoing intensive treatment for obsessive compulsive disorder

Response Inhibition (RI) is the ability to suppress behaviors that are inappropriate for a given context. Obsessive-compulsive disorder (OCD) has been associated with impaired RI in adults as measured by the Stop Signal Task (SST). Conflicting results have been found in terms of the relationship between OCD severity and SST performance, and no studies to date have examined the relationship between SST and response to OCD treatment. Also relatively unknown is whether RI performance in OCD is associated with developmental or gender differences. This naturalistic study examined the relationship between SST performance, OCD severity, and OCD treatment response in a pediatric sample undergoing intensive treatment involving exposure and response prevention and medication management (n = 36). The SST and Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS) were administered at admission and program discharge. OCD severity was not significantly related to stop signal reaction time (SSRT) in the whole sample and among subgroups divided by age and gender. Baseline SSRT and SSRT change did not predict CYBOCS change across treatment in the whole sample, but exploratory analyses indicated both were significant predictors among female adolescents. Results suggest there may be developmental gender differences in the relationship between RI and clinical improvement in pediatric OCD.

Familial risk of psychosis in obsessive-compulsive disorder: Impact on clinical characteristics, comorbidity and treatment response

BackgroundFamily studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S). MethodsA total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up. ResultsThe three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p < 0.001], were more likely to have failed ≥2 trials of SRIs (χ2 = 8.45, p = 0.014), and less likely to have attained remission (χ2 = 6.57, p = 0.037) ConclusionsWe observed that having a relative with psychosis may predispose to treatment resistance in OCD. Further research on the influence of genetic liability to psychosis on treatment response in OCD may offer novel translational leads.

Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive-compulsive disorder.

Though several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype. A total of 200 individuals with OCD were genotyped using the TaqMan assay. All participants were assessed using the Mini International Neuropsychiatric Interview and the Yale-Brown Obsessive-Compulsive Scale, and their response to serotonin reuptake inhibitors (SRIs) was evaluated over naturalistic treatment and follow-up. After correcting for multiple comparisons, the G allele at rs6662980 was found to be associated with contamination and washing symptoms (p = .003). Logistic regression analysis also showed that presence of the G allele predicted poor response to SRIs (odds ratio [OR] = 2.473, 95% confidence interval [1.157, 5.407], p = .021). Interaction between presence of the G allele and the Contamination and Washing factor score predicted greater SRI resistance (OR = 3.654, [2.761, 4.547], p = .004). We conclude that specific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to SRIs, may be affected by variations in the SAPAP3 gene. Limitations of the study are the lack of a dimensional measure for assessing OCD symptoms, the evaluation of treatment response over naturalistic follow-up, and that only a single locus in the SAPAP3 gene was examined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

P.0536 Oxytocin receptor gene DNA methylation as a predictor of treatment response in obsessive-compulsive disorder

P.0536 Oxytocin receptor gene DNA methylation as a predictor of treatment response in obsessive-compulsive disorder

Hypermethylation of the oxytocin receptor gene (OXTR) in obsessive-compulsive disorder: further evidence for a biomarker of disease and treatment response

ABSTRACT Obsessive-compulsive disorder (OCD) has recently been linked to increased methylation levels in the oxytocin receptor (OXTR) gene, and OXTR hypermethylation has predicted a worse treatment response to cognitive-behavioural therapy (CBT). Furthermore, OCD is associated with childhood trauma and stressful life events, which have both been shown to affect OXTR methylation. Here, we aimed to replicate findings of increased OXTR methylation as a predictor of disease and worse treatment response in an independent sample that received treatment within the public health care system. In addition, we aimed to extend previous findings by examining associations between OXTR hypermethylation, environmental stressors, OCD diagnosis, and treatment response. Methylation levels at two CpGs within OXTR exon III were compared between n = 181 OCD patients and n = 199 healthy controls using linear regression analysis. In a subsample of OCD patients (n = 98) with documented treatment data, we examined associations between methylation and treatment response to CBT. Childhood adversity and stressful life events were assessed using Childhood Trauma Questionnaire and Life Experience Survey, respectively. OCD patients exhibited significant hypermethylation at CpG site cg04523291 compared to controls, and increased methylation was associated with impaired treatment response. Moreover, hypermethylation at cg04523291 was associated with stressful life events in OCD patients, and with childhood adversity in controls. Yet, there were no significant mediation effects. In conclusion, we replicated the association between OXTR hypermethylation and OCD in the largest sample, so far. Furthermore, our findings support the role of OXTR methylation as a promising biomarker for treatment response in OCD.

Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

Introduction: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. Objective: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. Methods: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. Results: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. Conclusions: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.

Investigating the Role of Glutamate in Obsessive-Compulsive Disorder: Current Perspectives.

Glutamate is a ubiquitous excitatory neurotransmitter, which is involved in normal physiology, a variety of central nervous system (CNS) functions, including excitotoxicity and neuronal migration. It is implicated in the pathogenesis of various neuropsychiatric disorders including epilepsy, Parkinson’s disease, Alzheimer’s dementia, schizophrenia and obsessive compulsive disorder (OCD). Over the years, a growing body of evidence has helped researchers understand the mechanisms underlying glutamatergic involvement in the pathogenesis of these disorders. In this review, we attempt to elucidate the role of glutamate in OCD, which is a chronic psychiatric condition with significant morbidity. This article provides current perspectives on the role played by glutamate in the pathogenesis, clinical symptoms and treatment response in OCD, a critical analysis of existing and emerging evidence, both clinical and preclinical, followed by a summary and future directions.

BDNF association study with obsessive-compulsive disorder, its clinical characteristics, and response to fluvoxamine-treatment in Iranian patients.

Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder with complex genetic inheritance. Findings suggest a role for brain-derived neurotrophic factor (BDNF) in OCD, but reports are limited. Here we studied the association of BDNF polymorphisms rs6265 and rs2883187 with OCD and its clinical characteristics in Iranian patients as well as the fluvoxamine-treatment outcome of OCD patients. Iranian OCD patients who were diagnosed according to DSM-IV-TR entered the study. DNAs were extracted from blood samples and were genotyped by means of PCR-RFLP. A total of 200 OCD cases and 225 controls for rs6265 and 219 cases and 224 controls for rs2883187 were studied in the genetic association analysis. Pharmacotherapy was defined as 12 weeks treatment with fluvoxamine (daily dose: 150-300 mg), and patients were classified into 3 groups (responders, nonresponders, and refractory) based on the reduction in their Y-BOCS severity scores. Data of 94 patients for rs6265 and 106 patients for rs2883187 was analyzed to evaluate the association of these single nucleotide polymorphism (SNPs) with treatment response. A significant association was detected between the BDNF polymorphism rs2883187 and OCD (p = .00). The other BDNF polymorphism, rs6265, was not associated with OCD, but a weak association with the cleaning-contamination subtype was detected (p = .038). No association was detected between BDNF SNPs and sex, age of onset, and family history. None of the studied BDNF SNPs or their haplotypes were associated with fluvoxamine treatment response. Results propose BDNF SNP, rs2883187, as a candidate genetic factor in OCD but not in OCD treatment response with fluvoxamine. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

General personality dimensions, impairment and treatment response in obsessive-compulsive disorder.

General personality dimensions are associated with clinical severity and treatment response in individuals with depression and many anxiety disorders, but little is known about these relationships in individuals with obsessive-compulsive disorder (OCD). Individuals in the current study included 705 adults with OCD who had participated in family and genetic studies of the disorder. Participants self-completed the Neuroticism, Extraversion, Openness Personality Inventory or Neuroticism, Extraversion, Openness Five-Factor Inventory-3. Relationships between personality scores, and subjective impairment and OCD treatment response, were evaluated. The odds of subjective impairment increased with (unit increase in) the neuroticism score (odds ratio, OR = 1.03; 95% CI = 1.01-1.04; p < 0.01) and decreased with extraversion scores (OR = 0.98; 95% CI = 0.96-0.99; p < 0.01). The odds of reporting a good response to serotonin/selective serotonin reuptake inhibitors (OR = 1.02; 95% CI = 1.01-1.04; p < 0.01) or cognitive behavioural therapy (OR = 1.03; 95% CI = 1.01-1.05; p < 0.01) increased with the extraversion score. The magnitude of these relationships did not change appreciably after adjusting for other clinical features related to one or more of the personality dimensions. The findings suggest that neuroticism and extraversion are associated with subjective impairment, and that extraversion is associated with self-reported treatment response, in individuals with OCD. © 2019 John Wiley & Sons, Ltd.

Caudate volume differences among treatment responders, non-responders and controls in children with obsessive-compulsive disorder.

Treatment response in obsessive-compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7-17years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene\u2013environment interaction approach

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale–Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD.

White Matter Features Associated With Autistic Traits in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is among the most debilitating psychiatric disorders. Comorbid autism spectrum disorder (ASD) or autistic traits may impair treatment response in OCD. To identify possible neurostructural deficits underlying autistic traits, we performed white matter tractography on diffusion tensor images (DTI) and assessed autistic trait severity using the Autism-Spectrum Quotient (AQ) in 33 OCD patients. Correlations between AQ and the DTI parameters, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were examined in major white matter tracts that were suggested to be altered in previous OCD studies. We found a negative correlation between AQ and FA and positive correlations between AQ and MD, AD and RD in the left uncinate fasciculus using age, Beck Depression Inventory, Yale-Brown Obsessive-Compulsive Scale, intelligence quotient and medication as covariates. However, we could not detect the significant results between AQ and all DTI parameters when adding gender as a covariate. In addition, in the ASD comorbid group, FA in the left uncinate fasciculus was significantly lower than in the non-ASD comorbid group and MD and RD were significantly higher than in the non-ASD group. These results did not survive correction for multiple comparisons. In ASD, the socio-emotional dysfunction is suggested to be related to the alteration of white matter microstructure in uncinate fasciculus. Our results suggest that variations in white matter features of the left uncinate fasciculus might be partly explained by autistic traits encountered in OCD patients.

The link between ADHD-like inattention and obsessions and compulsions during treatment of youth with OCD

Attention-deficit/hyperactivity disorder (ADHD) has been found to be highly comorbid in children and adolescents with obsessive-compulsive disorder (OCD). Some have proposed, however, that obsessive anxiety may cause inattention and executive dysfunction, leading to inappropriate ADHD diagnoses in those with OCD. If this were the case, these symptoms would be expected to decrease following successful OCD treatment. The present study tested this hypothesis and evaluated whether ADHD symptoms at baseline predicted OCD treatment response. Obsessive-compulsive and ADHD symptoms were assessed in 50 youth enrolled in a randomized controlled trial investigating selective serotonin reuptake inhibitor and cognitive behavioral treatment. Repeated-measures analysis of variance (RMANOVA) revealed that ADHD symptoms at baseline do not significantly predict treatment outcome. A multivariate RMANOVA found that OCD treatment response moderated change in inattention; participants who showed greater reduction in OCD severity experienced greater reduction in ADHD-inattentive symptoms, while those with less substantial reduction in obsessions and compulsions showed less change. These findings suggest that children and adolescents with OCD and inattention may experience meaningful improvements in attention problems following OCD treatment. Thus, in many youth with OCD, inattention may be inherently tied to obsessions and compulsions. Clinicians may consider addressing OCD in treatment before targeting inattentive-type ADHD.

Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial.

IntroductionSerotonin reuptake inhibitors (SRIs) are widely used for the treatment of psychiatric disorders, including obsessive-compulsive disorder (OCD). SRIs commonly cause delayed orgasm, the mechanism of which is poorly understood. Oxytocin is involved in sexual function and is interconnected with serotonin within the brain. SRIs are reported to affect the oxytocin system, but possible relations between SRI-induced changes of sexual function and oxytocin are unexplored in humans. In a randomized, double-blinded, placebo-controlled trial of OCD, the anti-obsessive efficacy and adverse events of SRIs and oxytocin measurements were studied.AimsTo identify possible correlates between oxytocin levels and sexual function; find out whether sexual side effects correlate with levels of oxytocin and/or paroxetine and clomipramine; and test whether changes in sexual functioning are related to an anti-obsessive response.MethodsReported sexual function and oxytocin plasma levels at rest were studied in 31 adults (15 men and 16 women) with OCD who participated in a randomized, double-blinded trial comparing the SRIs clomipramine and paroxetine with placebo. Sexual adverse effects were quantified by a clinician-administered semistructured interview. Anti-obsessive response was based on the Yale-Brown Obsessive-Compulsive Scale.Main Outcome MeasuresRatings on the Sexual Symptom Checklist, plasma oxytocin, serum paroxetine and clomipramine levels, and Yale-Brown Obsessive-Compulsive Scale scores.ResultsBaseline oxytocin levels were positively correlated with baseline OCD severity, but not with sexual functioning. Impaired orgasm at week 6 was reported by 73% of SRI-treated and 20% of placebo-treated patients (P = .03). Impaired orgasm was related to higher oxytocin levels after 4 weeks of SRI treatment (P < .01) but not to SRI concentrations. In men, an association between impaired orgasm and anti-obsessive treatment response was found (P = .028).ConclusionThis pilot study suggests that some collateral effects of SRIs, particularly delayed orgasm, might be influenced by changes within the oxytocinergic system and are related to anti-obsessive mechanisms. Early-onset delayed orgasm in SRI-treated patients could serve as a predictor for OCD treatment response.

No association between BDNF Val66Met polymorphism and treatment response in obsessive-compulsive disorder in the Japanese population.

AimBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population.MethodsWe first performed a case–control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD.ResultsWe found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05).ConclusionOur results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population.

Can early improvement be an indicator of treatment response in obsessive-compulsive disorder? Implications for early-treatment decision-making

In major depression, early response to treatment has been strongly associated with final outcome. We aimed to investigate the ability of early improvement (4 weeks) to predict treatment response at 12 weeks in DSM-IV-defined obsessive-compulsive disorder (OCD) patients treated with serotonin reuptake inhibitors (SRI). We conducted an SRI practical trial with 128 subjects. Inclusion criteria: age range 18–65 years-old, baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score ≥ 16, and absence of previous adequate pharmacological treatment. Systematic assessments were performed at baseline, 4 and 12 weeks of treatment. Treatment response at 12 weeks was defined as a 35% or greater reduction in baseline Y-BOCS score. Stepwise logistic regression was used to test the relationship between early improvement and treatment response at 12 weeks, taking into account additional potential predictive factors. Different thresholds of early improvement were tested and their predictive power was calculated. Early improvement, defined as a 20% or greater reduction from baseline Y-BOCS score at 4 weeks, predicted response at 12 weeks with 75.6% sensitivity and 61.9% specificity. According to a logistic regression including demographic and clinical features as explaining variables, early improvement was the best predictor of treatment response (OR = 1.05, p < 0.0001). Only 19.8% of patients who did not improve at 4 weeks were responders after 12 weeks. In contrast, 55.3% of the individuals who showed early improvement were responders at 12 weeks (Pearson Chi-Square = 17.06, p < 0.001). Early improvement predicted OCD treatment response with relatively good sensitivity and specificity, such that its role in early decision-making warrants further investigation in wider samples.Trial registration: clinicaltrials.gov Identifier NCT00680602.

Evidence-based treatment pathways for translational studies in obsessive-compulsive disorders.

Obsessive-compulsive disorder (OCD) and related disorders are costly and burdensome long-term illnesses. Whilst evidence-based pharmacological and psychological treatments are available for OCD, a significant proportion of OCD patients fail to respond and for many of the OCD-related disorders no validated treatments are as yet recognised. In addition, predictors of treatment response/non-response to guide clinicians in the management of individual patients are lacking. The introduction of personalised medicine to psychiatry is expected to offer the novel prospect of identifying the most effective treatment for a patient in a timely and cost-effective way. Translational research that investigates endophenotype predictors of treatment response in OCD and related disorders may pave the way toward personalised medicine. Such research is likely to require multidisciplinary collaboration between neuroscientists and clinicians, so that the right clinical questions are addressed, and large datasets, entailing multinational, multicentre sampling. In order to facilitate the translational investigation of the key aspects of the treatment response, these studies would require access to standardised treatment paradigms that are internationally recognised. In this chapter, we introduce some of the most important outstanding questions for personalised medicine that translational research could be expected to address within the next 10 years. We review the available tools and techniques for standardised clinical assessment and the criteria that are used to define the degree of therapeutic response (response, remission, relapse, resistance) that would naturally dictate the direction of treatment. We also present a series of consecutive stepped treatment algorithms based on evidence-based practice and modelled on naturalistic care that we believe could be adapted to multicentre settings as a template for the translational researcher to aid in the design of pragmatic treatment trials that are capable of identifying biomarkers of treatment response or non-response at each key stage of the evidence-based canon.