Sex differences in clinical response to deep brain stimulation in resistant obsessive-compulsive disorder.

INTRODUCTION: Deep brain stimulation (DBS) is an effective alternative to treat severe refractory obsessive-compulsive disorder (OCD), although little is known on factors predicting response. The objective of this study was to explore potential sex differences in the pattern of response to DBS in OCD patients. METHODS: We conducted a prospective observational study in 25 patients with severe resistant OCD. Response to treatment was defined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Logistic regression models were calculated to measure the likelihood of response at short and long-term follow-up by sex as measured by Y-BOCS score. Similar analyses were carried out to study changes in depressive symptomatology assessed with the Hamilton Depression Rating Scale (HDRS). Additionally, effect sizes were calculated to assess clinical significance. RESULTS: We did not observe significant clinical differences between men and women prior to DBS implantation, nor in the response after one year of stimulation. At long-term follow-up, 76.9% of men could be considered responders to DBS versus only 33.3% of women. The final response odds ratio in men was 10.05 with significant confidence intervals (88.90-1.14). No other predictors of response were identified. The sex difference in Y-BOCS reduction was clinically significant, with an effect size of 3.2. The main limitation was the small sample size. CONCLUSIONS: Our results suggest that gender could influence the long-term response to DBS in OCD, a finding that needs to be confirmed in new studies given the paucity of results on predictors of response to DBS.

Long-term comparative effectiveness of deep brain stimulation in severe obsessive-compulsive disorder.

BACKGROUND: Twenty years after the first use of Deep Brain Stimulation (DBS) in obsessive-compulsive disorder (OCD), our knowledge of the long-term effects of this therapeutic option remains very limited. OBJECTIVE: Our study aims to assess the long-term effectiveness and tolerability of DBS in OCD patients and to look for possible predictors of long-term response to this treatment. METHODS: We studied the course of 25 patients with severe refractory OCD treated with DBS over an average follow-up period of 6.4 years (±3.2) and compared them with a control group of 25 patients with severe OCD who refused DBS and maintained their usual treatment. DBS was implanted at the ventral anterior limb of the internal capsule and nucleus accumbens (vALIC-Nacc) in the first six patients and later at the bed nucleus of stria terminalis (BNST) in the rest of patients. Main outcome was change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score between the two groups assessed using mixed models. Secondary effectiveness outcomes included Hamilton Depression Rating Scale (HDRS) and Global Assessment of Functioning (GAF) scores. RESULTS: Obsessive symptoms fell by 42.5% (Y-BOCS score) in patients treated with DBS and by 4.8% in the control group. Fifty-six per cent of DBS-treated patients could be considered responders at the end of follow-up and 28% partial responders. Two patients among those who rejected DBS were partial responders (8%), but none of the non-DBS group achieved criteria for complete response. HDRS and GAF scores improved significantly in 39.2% and 43.6% among DBS-treated patients, while did not significantly change in those who rejected DBS (improvement limited to 6.2% in HDRS and 4.2% in GAF scores). No statistically significant predictors of response were found. Mixed models presented very large comparative effect sizes for DBS (4.29 for Y-BOCS, 1.15 for HDRS and 2.54 for GAF). Few patients experienced adverse effects and most of these effects were mild and transitory. CONCLUSIONS: The long-term comparative effectiveness and safety of DBS confirm it as a valid option for the treatment of severe refractory OCD.

Viability Study of Machine Learning-Based Prediction of COVID-19 Pandemic Impact in Obsessive-Compulsive Disorder Patients.

BACKGROUND: Machine learning modeling can provide valuable support in different areas of mental health, because it enables to make rapid predictions and therefore support the decision making, based on valuable data. However, few studies have applied this method to predict symptoms' worsening, based on sociodemographic, contextual, and clinical data. Thus, we applied machine learning techniques to identify predictors of symptomatologic changes in a Spanish cohort of OCD patients during the initial phase of the COVID-19 pandemic. METHODS: 127 OCD patients were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured clinical interview during the COVID-19 pandemic. Machine learning models for classification (LDA and SVM) and regression (linear regression and SVR) were constructed to predict each symptom based on patient's sociodemographic, clinical and contextual information. RESULTS: A Y-BOCS score prediction model was generated with 100% reliability at a score threshold of ± 6. Reliability of 100% was reached for obsessions and/or compulsions related to COVID-19. Symptoms of anxiety and depression were predicted with less reliability (correlation R of 0.58 and 0.68, respectively). The suicidal thoughts are predicted with a sensitivity of 79% and specificity of 88%. The best results are achieved by SVM and SVR. CONCLUSION: Our findings reveal that sociodemographic and clinical data can be used to predict changes in OCD symptomatology. Machine learning may be valuable tool for helping clinicians to rapidly identify patients at higher risk and therefore provide optimized care, especially in future pandemics. However, further validation of these models is required to ensure greater reliability of the algorithms for clinical implementation to specific objectives of interest.

Changes in the stool and oropharyngeal microbiome in obsessive-compulsive disorder.

Although the etiology of obsessive-compulsive disorder (OCD) is largely unknown, it is accepted that OCD is a complex disorder. There is a known bi-directional interaction between the gut microbiome and brain activity. Several authors have reported associations between changes in gut microbiota and neuropsychiatric disorders, including depression or autism. Furthermore, a pediatric-onset neuropsychiatric OCD-related syndrome occurs after streptococcal infection, which might indicate that exposure to certain microbes could be involved in OCD susceptibility. However, only one study has investigated the microbiome of OCD patients to date. We performed 16S ribosomal RNA gene-based metagenomic sequencing to analyze the stool and oropharyngeal microbiome composition of 32 OCD cases and 32 age and gender matched controls. We estimated different α- and ß-diversity measures and performed LEfSe and Wilcoxon tests to assess differences in bacterial distribution. OCD stool samples showed a trend towards lower bacterial α-diversity, as well as an increase of the relative abundance of Rikenellaceae, particularly of the genus Alistipes, and lower relative abundance of Prevotellaceae, and two genera within the Lachnospiraceae: Agathobacer and Coprococcus. However, we did not observe a different Bacteroidetes to Firmicutes ratio between OCD cases and controls. Analysis of the oropharyngeal microbiome composition showed a lower Fusobacteria to Actinobacteria ratio in OCD cases. In conclusion, we observed an imbalance in the gut and oropharyngeal microbiomes of OCD cases, including, in stool, an increase of bacteria from the Rikenellaceae family, associated with gut inflammation, and a decrease of bacteria from the Coprococcus genus, associated with DOPAC synthesis.

Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years.

BACKGROUND: Twenty years after its first use in a patient with obsessive-compulsive disorder (OCD), the results confirm that deep brain stimulation (DBS) is a promising therapy for patients with severe and resistant forms of the disorder. Nevertheless, many unknowns remain, including the optimal anatomical targets, the best stimulation parameters, the long-term (LT) effects of the therapy, and the clinical or biological factors associated with response. This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response. AIM: To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD. METHODS: A comprehensive search was conducted in the PubMed, Cochrane, Scopus, and ClinicalTrials.gov databases from inception to December 31, 2020, using the following strategy: "(Obsessive-compulsive disorder OR OCD) AND (deep brain stimulation OR DBS)." Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool. The inclusion criteria were as follows: a main diagnosis of OCD, DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale (Y-BOCS) as primary outcome. Data were analyzed with descriptive statistics. RESULTS: Forty articles identified by the search strategy met the eligibility criteria. Applying a follow-up threshold of 36 mo, 29 studies (with 230 patients) provided information on short-term (ST) response to DBS in, while 11 (with 155 patients) reported results on LT response. Mean follow-up period was 18.5 ± 8.0 mo for the ST studies and 63.7 ± 20.7 mo for the LT studies. Overall, the percentage of reduction in Y-BOCS scores was similar in ST (47.4%) and LT responses (47.2%) to DBS, but more patients in the LT reports met the criteria for response (defined as a reduction in Y-BOCS scores > 35%: ST, 60.6% vs LT, 70.7%). According to the results, the response in the first year predicts the extent to which an OCD patient will benefit from DBS, since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation. Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients; but it is still controversial whether this improvement persists, increases or decreases in the long term. Three different patterns of LT response emerged from the analysis: 49.5% of patients had good and sustained response to DBS, 26.6% were non responders, and 22.5% were partial responders, who might improve at some point but experience relapses during follow-up. A significant improvement in depressive symptoms and global functionality was observed in most studies, usually (although not always) in parallel with an improvement in obsessive symptoms. Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters; however, some severe adverse events including intracranial hemorrhages and infections were also described. Hypomania was the most frequently reported psychiatric side effect. The relationship between DBS and suicide risk is still controversial and requires further study. Finally, to date, no clear clinical or biological predictors of response can be established, probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed. CONCLUSION: The present review confirms that DBS is a promising therapy for patients with severe resistant OCD, providing both ST and LT evidence of efficacy.

Neural correlates of fear conditioning and fear extinction and its association with cognitive-behavioral therapy outcome in adults with obsessive-compulsive disorder.

Recent neurobiological models of obsessive-compulsive disorder (OCD) have highlighted the potential role of abnormalities in fear learning processes. We compared brain activation -as assessed with whole-brain functional magnetic resonance imaging- during fear conditioning, fear extinction learning, and fear extinction recall in patients with OCD (n = 18) and healthy controls (n = 18). We also investigated whether brain activation during any of these processes was associated with exposure-based cognitive-behavioral therapy (CBT) outcome in patients. Patients with OCD showed significantly lower brain activation in the right insulo-opercular region and the dorsal anterior cingulate cortex during fear conditioning in comparison to healthy controls. Moreover, brain activation in the right insula predicted CBT outcome, with lower activation predicting a better outcome. Brain activation during extinction learning or recall did not differ between patients and controls or predicted CBT outcome in patients. Our results suggest that neural activations during fear conditioning in patients with OCD are abnormal and predict CBT outcome.

Childhood maltreatment interacts with hypothalamic-pituitary-adrenal axis negative feedback and major depression: effects on cognitive performance.

Background: Childhood maltreatment (CM) is associated with impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback and cognitive dysfunction, resembling those abnormalities linked to major depressive disorder (MDD). Objectives: We aimed to assess the potential modulating effects of MDD diagnosis or HPA axis function in the association between different types of CM and cognitive performance in adulthood. Methods: Sixty-eight MDD patients and 87 healthy controls were recruited. CM was assessed with the Childhood Trauma Questionnaire. We obtained three latent variables for neuropsychological performance (verbal memory, visual memory and executive function/processing speed) after running a confirmatory factor analysis with cognitive tests applied. Dexamethasone suppression test ratio (DSTR) was performed using dexamethasone 0.25 mg. Results: Different types of CM had different effects on cognition, modulated by MDD diagnosis and HPA axis function. Individuals with physical maltreatment and MDD presented with enhanced cognition in certain domains. The DSTR differentially modulated the association between visual memory and physical neglect or sexual abuse. Conclusions: HPA axis-related neurobiological mechanisms leading to cognitive impairment might differ depending upon the type of CM. Our results suggest a need for early assessment and intervention on cognition and resilience mechanisms in individuals exposed to CM to minimize its deleterious and lasting effects.

Antecedentes: El maltrato infantil (MI) se asocia con una alteración en la retroalimentación negativa del eje hipotalámico-hipofisario-adrenal (HHA) y disfunción cognitiva, que se asemejan a las anomalías vinculadas al trastorno depresivo mayor (TDM).Objetivos: Nuestro objetivo fue evaluar los posibles efectos moduladores del diagnóstico de TDM y de la función del eje HHA en la asociación entre diferentes tipos de MI y el rendimiento cognitivo en la edad adulta.Métodos: Se reclutaron 68 pacientes con TDM y 87 controles sanos. El MI se evaluó con el Cuestionario de trauma infantil. Se obtuvieron tres variables latentes para el rendimiento neuropsicológico (memoria verbal, memoria visual y función ejecutiva/velocidad de procesamiento) tras realizar un análisis factorial confirmatorio con las pruebas cognitivas aplicadas. La ratio de supresión de cortisol en el test de supresión con dexametasona (DSTR) se realizó usando dexametasona 0,25 mg.Resultados: Los diferentes tipos de MI tuvieron diferentes efectos sobre la cognición, modulados por el diagnóstico de TDM y la función del eje HHA. Los individuos con maltrato físico y TDM presentaron una cognición mejorada en ciertos dominios. El DSTR moduló diferencialmente la asociación entre memoria visual y negligencia física o abuso sexual.Conclusiones: Los mecanismos neurobiológicos relacionados con el eje HHA que conducen al deterioro cognitivo pueden diferir según el tipo de MI. Nuestros resultados sugieren la necesidad de una evaluación e intervención tempranas sobre la cognición y los mecanismos de resiliencia en individuos expuestos a MI para minimizar sus efectos nocivos y duraderos.

Childhood Maltreatment and Its Interaction with Hypothalamic-Pituitary-Adrenal Axis Activity and the Remission Status of Major Depression: Effects on Functionality and Quality of Life.

Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in the relationships between CM and functionality and QoL. Ninety-seven patients with MDD and 97 healthy controls were included. The cortisol awakening response, cortisol suppression ratio in the dexamethasone suppression test, and diurnal cortisol slope were assessed. Participants completed measures of psychopathology, CM, functionality, and QoL. Multiple linear regression analyses were performed to study the relationships between CM and functionality and QoL. Only non-remitted MDD patients showed lower functionality and QoL than controls, indicating that depressive symptoms may partly predict functionality and QoL. Cortisol measures did not differ between remitted and non-remitted patients. Although neither HPA axis measures nor depression remission status were consistently associated with functionality or QoL, these factors moderated the effects of CM on functionality and QoL. In conclusion, subtle neurobiological dysfunctions in stress-related systems could help to explain diminished functionality and QoL in individuals with CM and MDD and contribute to the persistence of these impairments even after the remission of depressive symptoms.

Vagus nerve stimulation as a potential modulator of periictal psychotic episodes: A report of four cases.

Drug resistant epilepsy (DRE) has been associated with a high incidence of psychotic disorders. Patients can develop psychosis after starting a new antiseizure medication, after undergoing resective surgery, or after implantation of a vagus nerve stimulation (VNS) system. The aim of this study was to investigate the modulation effect of VNS on psychotic episodes in DRE patients with a pre-existing history of periictal psychotic episodes (PPE). We retrospectively report the outcome of four patients from a single tertiary center with PPE prior to implantation. None of the implanted patients developed de novo PPE after VNS therapy. Regarding seizure outcome, all patients demonstrated a response to VNS with two who experienced who status epilepticus and three patients wtih a change in semiology with after VNS implantation. PPE disappeared in all the study patients, two of them at 6 months post-implantation and in the others after 2 and 3 years, respectively. 18F-FDG-PET results showed hypermetabolism in both anterior insular and medial frontal lobes which disappeared in the 18F -FDG-PET 4 years post-implantation. Based on the results of this series of cases we suggest that VNS therapy may be useful to modulatet PPE in patients with DRE, though effectiveness may be time-dependent.

First manic/hypomanic episode in obsessive-compulsive disorder patients treated with antidepressants: A systematic review.

High doses of antidepressants, particularly clomipramine and selective serotonin reuptake inhibitors (SSRIs), are the well-established treatment for obsessive-compulsive disorder (OCD), but manic/hypomanic episodes are potential adverse events associated with this treatment. A systematic literature review was performed on manic/hypomanic episodes in non-bipolar OCD patients. Clinical, sociodemographic and antidepressant characteristics during the manic/hypomanic switch were extracted using descriptive statistics. Data were obtained from 20 case reports and case series. Switching episodes mostly appeared in the first 12 weeks after antidepressant initiation and took place more frequently during SSRI use (mostly fluoxetine) in 64.3% of cases. Clomipramine and SSRI use differed non-significantly between the switching episodes that appeared during the first 12 weeks of antidepressant treatment and the episodes that appeared beyond 12 weeks. Switching episodes emerging before 12 weeks were associated with a lower defined daily dose of antidepressants than episodes emerging after 12 weeks. These findings suggest that there are two independent characteristics involved in manic/hypomanic switch in OCD: a) they appeared most frequently with SSRI use (fluoxetine) regardless of the time of it use, and b) episodes appeared in the first 12 weeks after SSRI or clomipramine initiation had a lower dose of antidepressant than episodes appeared after 12 weeks.

Sleep disturbances in obsessive-compulsive disorder: influence of depression symptoms and trait anxiety.

BACKGROUND: Sleep disturbances have been reported in obsessive-compulsive disorder (OCD) patients, with heterogeneous results. The aim of our study was to assess sleep function in OCD and to investigate the relationship between sleep and the severity of obsessive-compulsive (OC) symptoms, depressive symptoms and trait anxiety. METHODS: Sleep quality was measured in 61 OCD patients and 100 healthy controls (HCs) using the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regression was conducted to explore the association between sleep and psychopathological measures; a mediation analysis was also performed. RESULTS: OCD patients showed poor sleep quality and more sleep disturbances compared to HCs. The severity of depression, trait anxiety and OC symptomatology were correlated with poor sleep quality. Multiple linear regression analyses controlling for potential confounders revealed that the severity of depression and trait anxiety were independently related to poor sleep quality in OCD. A mediation analysis showed that both the severity of trait anxiety and depression mediate the relationship between the severity of OC symptoms and poor sleep quality among patients with OCD. CONCLUSIONS: Our findings support the existence of sleep disturbances in OCD. Trait anxiety and depression play a key role in sleep quality among OCD patients.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Sex differences in the association between obsessive-compulsive symptom dimensions and diurnal cortisol patterns.

Previous studies in non-clinical populations suggest that obsessive-compulsive symptoms are associated with hypothalamic-pituitary-adrenal (HPA) axis measures and that there are sex differences in these associations. We aimed to replicate these findings in a sample of 57 patients with obsessive-compulsive disorder (OCD) and 98 healthy subjects. Current and lifetime OCD symptom dimensions were assessed with the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS). Depressive symptoms and state and trait anxiety were also assessed. The following HPA axis measures were analysed in saliva: the diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope] and [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.) and the dexamethasone suppression test ratio (DSTR) after 0.25 mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of OCD symptom dimensions to each HPA axis measure while adjusting for age, sex, BMI, smoking, trait anxiety and depressive symptoms. A sex-specific association between current ordering/symmetry symptoms and AWE diurnal cortisol slope (positive association [flattened slope] in men, inverse association [stepper slope] in women) was found. Two similar sex by OCD dimensions interactions were found for lifetime aggressive and ordering/symmetry symptoms and both (FTP, AWE) diurnal cortisol slopes. Current and lifetime hoarding symptoms were associated to a more flattened FTP diurnal cortisol slope in women. The DSTR was not associated with OCD symptoms. The lifetime interference in functionality was associated with a more flattened AWE diurnal cortisol slope. In conclusion, our study suggests that there are sex differences in the association between OCD subtypes and specific HPA axis measures.

Seizures and epilepsy of autoimmune origin: A long-term prospective study.

OBJECTIVE: To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. METHODS: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. RESULTS: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. SIGNIFICANCE: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.

Looking into the genetic bases of OCD dimensions: a pilot genome-wide association study.

The multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene ontology and biological pathways associated with the presence of aggressive/checking, symmetry/order, contamination/cleaning, hoarding, and sexual/religious symptoms, as assessed via the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) in 399 probands. Logistic regression analyses were performed at the single-nucleotide polymorphism (SNP) level. Gene-based and enrichment analyses were carried out for common (SNPs) and rare variants. No SNP was associated with any dimension at a genome-wide level (p < 5 × 10-8). Gene-based analyses showed one gene to be associated with hoarding (SETD3, p = 1.89 × 10-08); a gene highly expressed in the brain and which plays a role in apoptotic processes and transcriptomic changes, and another gene associated with aggressive symptoms (CPE; p = 4.42 × 10-6), which is involved in neurotrophic functions and the synthesis of peptide hormones and neurotransmitters. Different pathways or biological processes were represented by genes associated with aggressive (zinc ion response and lipid metabolism), order (lipid metabolism), sexual/religious (G protein-mediated processes) and hoarding (metabolic processes and anion transport) symptoms after FDR correction; while no pathway was associated with contamination. Specific genomic bases were found for each dimension assessed, especially in the enrichment analyses. Further research with larger samples and different techniques, such as next-generation sequencing, are needed to better understand the differential genetics of OCD dimensions.

Exploring genetic variants in obsessive compulsive disorder severity: A GWAS approach.

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.

Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance.

BACKGROUND: Preliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing. METHODS: We assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains. RESULTS: OCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks. CONCLUSIONS: Our results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.

Tratamiento farmacológico del trastorno obsesivo-compulsivo en adultos: una guía de práctica clínica basada en el método ADAPTE / Pharmacological treatment of obsessive compulsive disorder in adults: a clinical practice guideline based on the ADAPTE methodology

A pesar de la existencia de tratamientos efectivos basados en la evidencia para el tratamiento del trastorno obsesivo-compulsivo (TOC), el abordaje de esta enfermedad sigue siendo subóptimo. Disponer de una guía terapéutica farmacológica del TOC puede ayudar a mejorar el manejo de la enfermedad en nuestro entorno y contribuir a reducir la carga de la enfermedad para el paciente. Con el patrocinio de la Sociedad Española de Psiquiatría un grupo de expertos ha desarrollado una guía para el tratamiento farmacológico del TOC a partir de algunas guías existentes siguiendo la metodología de la ADAPTE Collaboration. En este artículo se resume el proceso de elaboración de esta guía y las recomendaciones adoptadas por consenso por el grupo elaborador de las guías agrupadas en 5 áreas de interés: tratamiento agudo, duración del tratamiento, predictores de respuesta y síntomas especiales, respuesta parcial a falta de respuesta al tratamiento y poblaciones especiales

Despite the existence of effective evidence-based treatments for the management of obsessive-compulsive disorder (OCD), the therapeutic approach to this disease remains suboptimal. The availability of a therapeutic pharmacological guideline for OCD could help to improve the management of the disease in our setting and to reduce the burden of disease for the patient. With the sponsorship of the Spanish Society of Psychiatry, a group of experts has developed a guideline for the pharmacological treatment of OCD based on the recommendations of existing guidelines and following the methodology of the ADAPTE Collaboration. This article summarises the process of preparing this guideline and the recommendations adopted by consensus by a guideline panel grouped into five areas of interest: acute treatment, duration of treatment, predictors of response and special symptoms, partial response to lack of response to treatment, and special populations

Pharmacological treatment of obsessive compulsive disorder in adults: A clinical practice guideline based on the ADAPTE methodology. / Tratamiento farmacológico del trastorno obsesivo-compulsivo en adultos: una guía de práctica clínica basada en el método ADAPTE.

Despite the existence of effective evidence-based treatments for the management of obsessive-compulsive disorder (OCD), the therapeutic approach to this disease remains suboptimal. The availability of a therapeutic pharmacological guideline for OCD could help to improve the management of the disease in our setting and to reduce the burden of disease for the patient. With the sponsorship of the Spanish Society of Psychiatry, a group of experts has developed a guideline for the pharmacological treatment of OCD based on the recommendations of existing guidelines and following the methodology of the ADAPTE Collaboration. This article summarises the process of preparing this guideline and the recommendations adopted by consensus by a guideline panel grouped into five areas of interest: acute treatment, duration of treatment, predictors of response and special symptoms, partial response to lack of response to treatment, and special populations.