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.

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.

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.

Intrinsic functional and structural connectivity of emotion regulation networks in obsessive-compulsive disorder.

Despite emotion regulation being altered in patients with obsessive-compulsive disorder (OCD), no studies have investigated its relation to multimodal amygdala connectivity. We compared corticolimbic functional and structural connectivity between OCD patients and healthy controls (HCs), and correlated this with the dispositional use of emotion regulation strategies and with OCD severity. OCD patients (n = 73) and HCs (n = 42) were assessed for suppression and reappraisal strategies using the Emotion Regulation Questionnaire (ERQ) and for OCD severity using the Yale-Brown Obsessive-Compulsive Scale. Resting-state functional magnetic resonance imaging (rs-fMRI) connectivity maps were generated using subject-specific left amygdala (LA) and right amygdala (RA) masks. We identified between-group differences in amygdala whole-brain connectivity, and evaluated the moderating effect of ERQ strategies. Significant regions and amygdala seeds were used as targets in probabilistic tractography analysis. Patients scored higher in suppression and lower in reappraisal. We observed higher rs-fMRI RA-right postcentral gyrus (PCG) connectivity in HC, and in patients this was correlated with symptom severity. Reappraisal scores were associated with higher negative LA-left insula connectivity in HC, and suppression scores were negatively associated with LA-precuneus and angular gyri connectivity in OCD. Structurally, patients showed higher mean diffusivity in tracts connecting the amygdala with the other targets. RA-PCG connectivity is diminished in patients, while disrupted emotion regulation is related to altered amygdala connectivity with the insula and posterior brain regions. Our results are the first showing, from a multimodal perspective, the association between amygdala connectivity and specific emotional processing domains, emphasizing the importance of amygdala connectivity in OCD pathophysiology.

Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive-compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala-ventromedial prefrontal cortex (BLA-vmPFC) communication would predict CBT outcome in patients with OCD. METHODS: We investigated whether BLA-vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA-vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. RESULTS: We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA-vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA-vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. LIMITATIONS: We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. CONCLUSION: In this large sample of patients with OCD, BLA-vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA-vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.

Removing and reimplanting deep brain stimulation therapy devices in resistant OCD (when the patient does not respond): case report.

BACKGROUND: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery. CASE PRESENTATION: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder. CONCLUSION: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery.

Standards of care for obsessive-compulsive disorder centres.

In recent years, many assessment and care units for obsessive-compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries.

Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder.

BACKGROUND: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, "just-right" perceptions, feelings of incompleteness, or "urge-only" phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive-compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. METHODS: We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. RESULTS: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. LIMITATIONS: Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. CONCLUSION: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.

Amygdala activation and symptom dimensions in obsessive-compulsive disorder.

BACKGROUND: Despite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive-compulsive disorder (OCD) remains controversial. In the context of neuroimaging studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings. AIMS: To assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm. METHOD: Cross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls. RESULTS: The severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions. CONCLUSIONS: Amygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.

Brain structural imaging correlates of olfactory dysfunction in obsessive-compulsive disorder.

Olfactory dysfunction has been described in obsessive-compulsive disorder (OCD). Brain regions involved in smell processing partially overlap with structures included in the neurobiological models of OCD, although no previous studies have analyzed the neuroanatomical correlates of olfactory dysfunction in this disorder. The aim of our study was to examine the association between regional gray matter volume, as assessed by a voxel-based morphometry analysis of magnetic resonance images (MRI), and olfactory function, as assessed by the Sniffin' Sticks test (SST). Olfactory function was assessed in 19 OCD patients and 19 healthy volunteers. All participants were also scanned in a 1.5-T magnet to obtain T1-weighted anatomical MRIs, which were pre-processed and analyzed with SPM8. Three different correlation models were used to study the association between regional gray matter volumes and olfactory function in the domains assessed by the SST: detection threshold, discrimination, and identification. OCD patients showed a significant impairment in all the domains assessed by the SST. Voxel-based mapping revealed a positive association in healthy controls between detection threshold and the gray matter content of a left anterior cingulate cortex cluster. In OCD patients, a positive correlation was observed between identification errors and the gray matter volume of the left medial orbital gyrus. In a post hoc analysis, these two gray matter regions were shown to be enlarged in OCD patients. Our findings support the idea that olfactory dysfunction in OCD is associated with volumetric changes in brain areas typically implicated in the neurobiology of the disorder.

Spanish version of the Dimensional Obsessive-Compulsive Scale (DOCS): psychometric properties and relation to obsessive beliefs.

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.

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.

Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder.

BACKGROUND: Recent data from neuroimaging, genetic and clinical trials and animal models suggest a role for altered glutamatergic neuro transmission in the pathogenesis of obsessive-compulsive disorder (OCD). The aim of this study was to investigate whether variants in the GRIN2B gene, the gene encoding the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor, may contribute to genetic susceptibility to OCD or to different OCD subphenotypes. METHODS: Between 2003 and 2008, we performed a case-control association study in which we genotyped 10 tag single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3' UTR) of GRIN2B. We performed SNP association and haplotype analysis considering the OCD diagnosis and different OCD subphenotypes: early-onset OCD, comorbid tic disorders and OCD clinical symptom dimensions. RESULTS: We enrolled 225 patients with OCD and 279 controls recruited from the OCD Clinic at Bellvitge Hospital (Barcelona, Spain). No significant difference in the distribution of alleles or genotypes was detected between patients with OCD and controls. Nonetheless, on analyzing OCD subphenotypes, the rs1805476 SNP in male patients (95% confidence interval [CI] 1.37-4.22, p = 0.002) and a 4-SNP haplotype in the whole sample (rs1805476, rs1805501, rs1805502 and rs1805477; odds ratio 1.92, 95% CI 1.22-3.01; permutation p = 0.023) were significantly associated with the presence of contamination obsessions and cleaning compulsions. LIMITATIONS: Study limitations included the risk of population stratification associated with the case-control design, use of psychiatrically unscreened blood donors as the control group, reduced sample size of participants with certain OCD subphenotypes and tested polymorphisms limited to 3' UTR and exon 13 of GRIN2B. CONCLUSION: Our results converge with recent data suggesting a possible contribution of glutamatergic variants to the genetic vulnerability to OCD or at least to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may constitute a useful tool to disentangle the complex genetic basis of the disorder.

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.

Olfactory identification and discrimination in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging and neuropsychological data from patients with an obsessive-compulsive disorder (OCD) indicate the dysfunction of the orbitofrontal cortex (OFC). Olfactory processing has been associated with OFC function, although results from OCD studies regarding this sensory modality have been inconclusive. No previous study has analyzed both odor discrimination and identification capacity in OCD patients using "Sniffin' Sticks" tests. The aim of our study was to assess odor threshold, identification, discrimination, and nonverbal memory in OCD patients, in order to determine whether these functions were affected. METHODS: Olfactory function was measured in 29 OCD patients and 29 healthy volunteers (HV) using the "Sniffin' Sticks" test and their nonverbal memory was scored with the Rey-Osterrieth Complex Figure Test. RESULTS: OCD patients showed significant impairment in their odor performance and in their execution of the nonverbal memory task compared to HV. No statistical associations were found between the deficits in the two areas. The severity of depressive and obsessive-compulsive symptoms did correlate with olfactory identification. CONCLUSION: Our findings support the hypothesis that olfactory and memory dysfunctions in OCD reflect different neurobiological alterations of the disorder, and point to the modulation effect of depressive and obsessive-compulsive symptoms on odor performance.

Stressful life events at onset of obsessive-compulsive disorder are associated with a distinct clinical pattern.

BACKGROUND: Environmental stressors are considered to play an important role in the triggering of mental disorders such as obsessive-compulsive disorder (OCD). Although there is extensive literature on traumatic life events, little is known about the role of nontraumatic but nonetheless stressful life events (SLEs) in OCD. The aim of this study was to establish whether OCD preceded by an SLE presents a different clinical pattern compared to non-SLE-preceded OCD. METHODS: We interviewed 412 OCD patients to assess both SLEs at onset of OCD and other clinical variables, including OCD symptom dimensions. Logistic regression was then applied to explore the relationship between clinical variables and OCD preceded by an SLE. RESULTS: The SLE-preceded OCD group showed a later onset of the disorder (OR = 1.04, P = .015), a history of complicated birth (OR = 5.54, P<.001), less family history of OCD (OR = 0.42, P = .014), and the presence of contamination/cleaning symptoms (OR = 1.99, P = .01). CONCLUSIONS: Patients with OCD onset close to an SLE and those without an SLE close to OCD onset show a distinct clinical pattern.

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.

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.