Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

Empirically-derived response trajectories of intensive residential treatment in obsessive-compulsive disorder: A growth mixture modeling approach.

BACKGROUND: This study investigated distinct trajectories of treatment response in a naturalistic intensive/residential treatment (IRT) program for adults with severe obsessive-compulsive disorder (OCD). We hypothesized that: (1) distinct trajectories would emerge and (2) demographic variables, psychiatric comorbidity, OCD symptom subtype, level of insight, previous exposure and response prevention (ERP) treatment, and quality of life, would differentially predict assignment to these trajectories. METHODS: Participants included 305 individuals with primary OCD admitted for IRT. RESULTS: Two trajectories emerged over the course of the first eight weeks of treatment, with the vast majority of participants demonstrating treatment response. The first trajectory (96%, n = 292) showed a negative, linear treatment response (a.k.a. "linear responders") and more severe OCD symptoms at admission. The second trajectory (4%, n = 13) had less severe OCD symptoms at admission and did not exhibit a significant overall change in symptoms over the course of treatment. More specifically, this second trajectory or "u-shaped responders" show a non-significant linear response through week four of treatment, followed by slightly increased symptoms in week five. Assignment to these classes was not differentially predicted by hypothesized predictor variables. LIMITATIONS: Our final model had inconsistent fit indices and small class prevalance of the u-shaped responder group; therefore, model selection was based on both fit indices and substantive meaning. CONCLUSIONS: This study emprically derived two distinct trajectories of OCD symptom severity over the course of IRT. These findings have the potential to refine IRT for patients with severe OCD, and to potentially guide future investigation into the optimal delivery of ERP treatment for OCD generally.

Validating an abbreviated version of the Obsessive Beliefs Questionnaire.

OBJECTIVES: A shorter version of the Obsessive Beliefs Questionnaire (OBQ-44) is needed to promote the use of this measure in research and increase our understanding of cognitive phenomena maintaining obsessive-compulsive disorder (OCD). Additionally, an abbreviated version of the OBQ-44 would encourage frequent monitoring of dysfunctional beliefs in intensive care settings. This study aimed to validate a nine-item version of the questionnaire (OBQ-9). METHOD: Participants seeking intensive/residential treatment for OCD (N = 311) completed relevant measures on a weekly basis and at admission and discharge. RESULTS: A confirmatory factor analysis revealed that the OBQ-9's factor structure replicated the three-factor solution of the OBQ-44. The OBQ-9 demonstrated good psychometric properties and convergent validity and was sensitive to treatment effects. Finally, the OBQ-9 subscales predicted specific OCD dimensions over and above depressive symptoms. CONCLUSION: The OBQ-9 appears to be a psychometrically sound tool for routine outcome monitoring of dysfunctional beliefs in hospital-based settings.

Can Distressing Sexual Thoughts Be Regulated? Experiential Willingness Versus Distraction.

This study examines the effects of different techniques on the management of unwanted sexual thoughts. Participants (N = 150; 67 who found sexual thoughts distressing, 83 participants who did not) were randomly placed into one of three experimental conditions: experiential willingness, distraction, or no strategies for dealing with unwanted sexual thoughts. Participants answered questions assessing attitudes about their sexual thoughts and recorded sexual thought frequency for a 3-minute period pre- and post-intervention. Thought frequencies decreased for all groups post intervention for both the distressed and nondistressed samples. Acceptability of thoughts increased for the experiential willingness group, remained similar for the distraction group, and decreased for the control group. The findings indicate that distraction was more easily implemented, more commonly used, and equally effective to experiential willingness at reducing sexual thoughts in the short term. However, the short experiential willingness intervention increased acceptability of sexual thoughts, which could have an impact on longer-term results.

Validation of the distress tolerance scale-short form in obsessive compulsive disorder.

OBJECTIVE: This study aimed to develop and validate the Distress Tolerance Scale-Short Form (DTS-SF), a modification of the original Distress Tolerance Scale, in a severe/complex sample of individuals with obsessive compulsive disorder (OCD). Currently, there are multiple self-report measurements of distress tolerance (DT), highlighting the need for a more refined measure. METHOD: Participants included 222 individuals with a primary diagnosis of OCD (57% male, average age = 31) seeking intensive/residential treatment. Participants completed surveys at admission, discharge, and each week. RESULTS: An exploratory factor analysis revealed a one-factor solution representing overall DT ability. The DTS-SF was found to be sensitive to treatment effects. Appropriate associations between the DTS-SF and other measures were also found, with lower DT associated with greater OCD and depression severity and lower reported quality of life. CONCLUSION: The DTS-SF was found to be a valid and reliable measure with high clinical utility for quickly and accurately measuring DT.

Stability of compounded trilostane suspension in cod liver oil.

Trilostane is a synthetic steroid analog used to treat canine hyperadrenocorticism. For small dogs, the dose found in commercially available dosage forms of trilostane is sometimes too high. Compounding trilostane in a liquid diluent provides an option for more precise dosing and adjustments, and can be easier to administer, versus a tablet or capsule. Trilostane suspends well in cod liver oil, which is generally palatable to dogs. The stability of a compounded trilostane suspension in cod liver oil stored at room temperature was investigated for 90 days. Compounded trilostane retained stability, defined as maintaining 90-105% labeled value, for 60 days when stored in amber glass bottles. However, drug potency fell >10% below the labeled value when stored in amber plastic bottles after 7 days.

How willing are you? Willingness as a predictor of change during treatment of adults with obsessive-compulsive disorder.

OBJECTIVE: Exposure and response prevention (ERP) is an effective treatment for individuals with obsessive-compulsive disorder (OCD), yet a substantial number of individuals with OCD do not fully respond to this intervention. Based on emerging experimental and clinical research on acceptance, this study sought to explore whether willingness to experience unpleasant thoughts, emotions, and bodily sensations during ERP was associated with improved treatment response. METHODS: Two hundred eighty-eight adults with OCD receiving residential ERP provided self-rated willingness and other exposure-related variables during each daily coached ERP session. Obsessive-compulsive and depressive symptom severity was assessed every week. Multilevel modeling was used to study the impact of willingness on treatment outcome during the first 6 weeks of residential care. RESULTS: Data indicated that individuals with higher willingness during ERP reported faster symptom reduction during residential treatment, even when controlling for length of stay, psychopharmacological intervention, depression, adherence, and rituals performed during ERP. These results appear to have both statistical and clinical significance. CONCLUSIONS: Willingness to fully experience unpleasant and unwanted thoughts, emotions, and bodily sensations during exposures appears to be a marker of successful exposure therapy in adults with OCD. Future research should examine how willingness may enhance extinction learning during ERP.

Acceptance and Commitment Therapy for Problematic Internet Pornography Use: A Randomized Trial.

Problematic Internet pornography use is the inability to control the use of pornography, the experience of negative cognitions or emotions regarding pornography use, and the resulting negative effects on quality of life or general functioning. This study compared a 12-session individual protocol of acceptance and commitment therapy (ACT) for problematic Internet pornography use to a waitlist control condition with 28 adult males, all but 1 of whom were members of the Church of Jesus Christ of Latter-day Saints. Measures of self-reported pornography viewing, standardized measures of compulsive sexual behavior and related cognitions, and quality of life occurred at pretreatment, posttreatment, and 3-month follow-up. Results demonstrate significant between-condition reductions in pornography viewing compared to the waitlist condition (93% reduction ACT vs. 21% waitlist). When combining all participants (N=26), a 92% reduction was seen at posttreatment and an 86% reduction at 3-month follow-up. Complete cessation was seen in 54% of participants at posttreatment and at least a 70% reduction was seen in 93% of participants. At the 3-month follow-up assessment, 35% of participants showed complete cessation, with 74% of participants showing at least 70% reduction in viewing. Treatment suggestions and future directions are discussed.

REDUCED DISGUST PROPENSITY IS ASSOCIATED WITH IMPROVEMENT IN CONTAMINATION/WASHING SYMPTOMS IN OBSESSIVE-COMPULSIVE DISORDER.

OBJECTIVES: Disgust is a well-established phenomenon with known neurobiological correlates. However, it remains unclear how or whether disgust changes with clinical treatment, because few longitudinal studies have tracked the association of disgust vulnerability and clinical symptoms in patient populations. METHODS: We assessed disgust propensity and symptoms of obsessive-compulsive disorder (OCD) in 134 patients receiving intensive residential treatment for OCD. Using linear regression with adjustment for age, sex, and depression severity, we tested the association between change in disgust propensity and change in OCD symptoms from admission to discharge. RESULTS: Change in disgust propensity was significantly associated with improvement in contamination/washing symptoms (ß = 0.25 [95% confidence interval: 0.11-0.39]; P = .001). No significant association was found between change in disgust propensity and change in other OCD symptom dimensions. CONCLUSIONS: In patients with OCD undergoing intensive residential treatment, disgust propensity appears to improve in parallel with contamination/washing symptoms.

Intensive residential treatment for severe obsessive-compulsive disorder: characterizing treatment course and predictors of response.

BACKGROUND: Intensive residential treatment (IRT) is effective for severe, treatment-resistant obsessive-compulsive disorder (OCD). We sought to characterize predictors and course of response to IRT. METHODS: Admission, monthly, and discharge data were collected on individuals receiving IRT. We examined the association between baseline characteristics and percent change in OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) using linear regression. We compared baseline characteristics of IRT responders (≥35% reduction in Y-BOCS) versus non-responders, and of patients who did versus those who did not achieve wellness (Y-BOCS ≤ 12) using non-parametric tests. To examine the course of OCD severity over time, we used linear mixed-effects models with randomly varying intercepts and slopes. RESULTS: We evaluated 281 individuals admitted to an IRT program. Greater baseline Y-BOCS scores were associated with a significantly greater percent reduction in Y-BOCS scores (ß = -1.49 ([95% confidence interval: -2.06 to -0.93]; P < .001)). IRT responders showed significantly greater baseline Y-BOCS scores than non-responders (mean (SD) 28 (5.2) vs. 25.6 (5.8); P = .003) and lower past-year alcohol use scores than non-responders (1.4 (1.9) vs. 2.1 (2.2); P = .01). Participants who achieved wellness displayed lower hoarding factor scores than those who did not (5 (4.6) vs. 9.53 (6.3); P = .03). OCD symptoms declined rapidly over the first month but more slowly over the remaining two months. CONCLUSIONS: Higher baseline OCD severity, lower past-year alcohol use, and fewer hoarding symptoms predicted better response to IRT. IRT yielded an initial rapid reduction in OCD symptoms, followed by a slower decline after the first month.

Acceptance and commitment therapy as a treatment for problematic internet pornography viewing.

Despite the prevalence of problematic Internet pornography viewing and the breadth of intervention approaches to potentially address it, no studies to address this problem have been reported to date. An emerging treatment approach, Acceptance and Commitment Therapy (ACT), holds promise as a treatment for Internet pornography viewing because of its focus on processes hypothesized to underlie this maladaptive behavior. In the first experiment on the treatment of problematic Internet pornography viewing, 6 adult males who reported that their Internet pornography viewing was affecting their quality of life were treated in eight 1.5-hour sessions of ACT for problematic pornography viewing. The effects of the intervention were assessed in a multiple-baseline-across-participants design with time viewing pornography as the dependent variable. Treatment resulted in an 85% reduction in viewing at posttreatment with results being maintained at 3-month follow-up (83% reduction). Increases were seen on measures of quality of life, and reductions were seen on measures of OCD and scrupulosity. Weekly measures of ACT-consistent processes showed reductions that corresponded with reductions in viewing. Large reductions were seen on a measure of psychological flexibility, and minor reductions were seen on measures of thought-action fusion and thought control. Overall, results suggest the promise of ACT as a treatment for problematic Internet pornography viewing and the value of future randomized trials of this approach.