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BACKGROUND: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study explores the genomic bases of OCD severity. METHODS: We administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to 401 patients at their first visit to our clinic to measure their OCD severity. Genotyping data was collected by using the Infinium PsychArray-24 BeadChip kit (Illumina). We analyzed genetic association with OCD severity in a linear regression analysis at single-nucleotide polymorphism (SNP)- and gene-levels, this last also considering rare variants. Enrichment analyses were performed from gene-based analyses' results. RESULTS: No SNP reached significant association (p < 10-8) with the YBOCS. Six markers showed suggestive association (p < 10-5). The top SNP was an intergenic variant in chromosome 2: rs7578149 (p < 1.89 × 10-6), located in a region suggestively associated with MDD. Linkage disequilibrium was found for two clusters of SNPs located between SLC16A14 and SP110 in chromosome 2, all of them forming one peak of association. Enrichment analyses revealed OCD genes to be associated with porin activity (FDR = 0.01) and transmembrane structure (FDR = 0.04). LIMITATIONS: The size of the sample and the transversal nature of the severity measure are limitations of this study. CONCLUSION: This study contributes to better characterize OCD at an individual level, helping to know more about the prognosis of the disorder and develop more individualized treatments This study was supported in part by the Carlos III Health Institute (PI16/00950, PI18/00856); FEDER funds (‘A way to build Europe’) and by the Agency for Management of University and Research Grants of the Catalan Government (2014SGR1672). MA was supported by the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia. Grant co-funded by the European Social Fund (ESF) “ESF, Investing in your future” (2017 FI_B 00327). ER was supported by a Juan Rodés contract (JR14/00038)

Objectives Our main goal was to provide the psychometric properties of the Spanish version of the Dimensional Obsessive–Compulsive Scale (DOCS) in a non-clinical sample (n = 237) and in adult patients with Obsessive–Compulsive Disorder (OCD) (n = 110). We also examined the association between OC symptom dimensions and obsessive beliefs. Methods The psychometric properties involved four steps: reliability, structural validity, convergent and discriminant validity and diagnostic sensitivity. Linear regression analyses were used to assess the associations between OC symptoms and obsessive beliefs. Results Exploratory and confirmatory factor analyses replicated the original four-factor structure in both samples. The DOCS showed good performance in terms of internal consistency, test–retest reliability and convergent validity in both samples. The DOCS showed better diagnostic sensitivity than another self-report instrument of OC symptoms, the Obsessive–Compulsive Inventory Revised. Findings of the relationship between obsessive beliefs and OC symptoms revealed that certain obsessive beliefs predicted specific OC symptom dimensions. Conclusions The Spanish version of the DOCS has similar psychometric properties than the original English instrument, although its performance is somewhat better in OCD patients than in students. It will be important to ascertain its ability to discriminate OCD from other associated disorders.

Background Partial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness. Objective To identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression. Methods We evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements. Results At the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen. Conclusions These results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.

Poor insight has been reported in 15% to 36% of patients with obsessive-compulsive disorder (OCD), but little is known about its clinical correlations. This study examines insight among patients with OCD using a standardized instrument, the Brown Assessment of Beliefs Scale, and analyzes its relationship with clinical factors. Insight was assessed in 132 patients with OCD, before and after pharmacologic treatment, using the Brown Assessment of Beliefs Scale. Differences between patients with good and poor insight on sociodemographic variables, OCD severity, comorbidity, and treatment response were studied. Stability of insight after pharmacologic treatment was also examined. Thirty-nine patients (29.5%) exhibited poor insight. They showed more depressive symptoms (P = .001) and personality disorders (P = .001), especially the schizotypal form, than did good insight subjects, but there were no significant differences in treatment response. Insight significantly improves after treatment (P < .001). Our results suggest that insight in OCD varies widely and constitutes a dynamic phenomenon that can improve after treatment and is influenced by clinical conditions such as affective status or personality.