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Obsessive-compulsive disorder (OCD) is a psychiatric disorder with multiple symptom dimensions (e.g. contamination, symmetry). OCD clusters in families and decades of twin studies clearly demonstrate an important role for genetics in the etiology of the disorder. In this review, we summarize the genetic epidemiology and molecular genetic studies of OCD and obsessive-compulsive symptoms. OCD is a heritable, polygenic disorder with contributions from both common and rare variants, including de novo deleterious variations. Multiple studies have provided reliable support for a large additive genetic contribution to liability to OCD, with discrete OCD symptom dimensions having both shared and unique genetic risks. Genome-wide association studies have not produced significant results yet, likely because of small sample sizes, but larger meta-analyses are forthcoming. Both twin and genome-wide studies show that OCD shares genetic risk with its comorbid conditions (e.g. Tourette syndrome and anorexia nervosa). Despite significant efforts to uncover the genetic basis of OCD, the mechanistic understanding of how genetic and environmental risk factors interact and converge at the molecular level to result in OCD's heterogeneous phenotype is still mostly unknown. Future investigations should increase ancestral genetic diversity, explore age and/or sex differences in genetic risk for OCD and expand the study of pharmacogenetics, gene expression, gene × environment interactions and epigenetic mechanisms for OCD.

Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.

Background Individuals with obsessive-compulsive disorder (OCD) face both personal and system-based barriers in receiving first-line treatment, i.e. cognitive behavioral therapy (CBT) with exposure and response prevention (ERP). The present study comprehensively investigated help-seeking behavior, treatment barriers and facilitators, attitudes and access to gold-standard treatment in adults with OCD in Germany. We aimed to characterize the care situation and examine the influence of clinical and sociodemographic variables on help-seeking behavior and receiving treatment. Methods An anonymous online survey was performed in individuals with OCD who were recruited in- and outside the psychiatric healthcare system. The survey included a wide range of questions regarding help-seeking behavior, treatment barriers and facilitators, attitudes towards different treatment options and access to treatment. Sociodemographic and clinical characteristics were also collected. The final sample comprised 276 individuals with OCD. Results The mean delay to seeking psychotherapeutic treatment was M  = 5.15 years ( SD  = 6.88) and the mean delay to recognition of OCD was M  = 5.58 years ( SD  = 7.16). Of those 211 who had ever received CBT, 49.5% reported that therapist-guided ERP had been performed at some point during treatment. Indicators of poor healthcare, such as longer delay to recognition or a larger number of treatments before receiving ERP were significantly associated with increased symptom severity. Moreover, a younger age was associated with a shorter delay to recognition of OCD. Taboo thoughts (60.9%) and checking (52.9%) were the most commonly reported symptom dimensions, and individuals with current taboo thoughts were significantly more likely to be treated with CBT. Educational websites were identified as the most important facilitators in recognizing OCD and providing information on effective treatment options. Lack of knowledge about treatment options was reported as the most common barrier to seeking/receiving ERP-based treatment. Conclusions Delays to the recognition of OCD and to seeking help still exceed 5 years on average, but were reduced in younger individuals, potentially reflecting increased mental health literacy. Although our sample may not be fully representative, our results fill the gap between epidemiological surveys and previous studies in outpatients. Options for improving the care situation are discussed.

Cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). However, CBT does not lead to a satisfying symptom reduction in a considerable number of patients with OCD. The identification of variables that predict insufficient treatment response could improve efficient treatment selection and inform the development of specific augmentative treatments. In the current study, we tested whether prediction of treatment response can be improved by including neurobiological markers during working memory (WM) performance. Forty-four patients with a primary OCD diagnosis participated in an n-back WM task with varying WM load while functional Magnetic Resonance Imaging (fMRI) was performed. Subsequently, all patients received CBT in an outpatient clinic. WM load-dependent modulation of the blood-oxygen-level-dependent (BOLD) signal in a bilateral cluster in inferior/superior parietal lobule predicted CBT response over and above clinical and sociodemographic variables (p < 0.05). Higher modulation was associated with larger relative symptom reduction. The results of the current study indicate that the ability of the WM system to flexibly adapt to changing task demands might be a useful indicator of CBT response in OCD. Possibly, this mechanism facilitates relearning processes during exposure-based CBT. However, findings need to be replicated in larger samples.

Studies have shown that people with obsessive–compulsive disorder (OCD) have impairments in spatial working memory (SWM) performance. However, it remains unclear whether this deficit represents a cognitive endophenotype preceding symptoms or a correlate of OCD. We investigated SWM in 69 people with OCD, 77 unaffected first-degree relatives of people with OCD and 106 healthy control participants. Taking age effects into account, SWM performance was best in healthy controls, intermediate in relatives and worst in OCD participants. However, since performance did not differ significantly between healthy controls and relatives, our study does not fully support SWM performance as a core cognitive endophenotype of OCD.

Increased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed. The error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27). Increased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes. Alterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control.

Individuals with obsessive-compulsive disorder (OCD) face both personal and system-based barriers in receiving first-line treatment, i.e. cognitive behavioral therapy (CBT) with exposure and response prevention (ERP). The present study comprehensively investigated help-seeking behavior, treatment barriers and facilitators, attitudes and access to gold-standard treatment in adults with OCD in Germany. We aimed to characterize the care situation and examine the influence of clinical and sociodemographic variables on help-seeking behavior and receiving treatment. An anonymous online survey was performed in individuals with OCD who were recruited in- and outside the psychiatric healthcare system. The survey included a wide range of questions regarding help-seeking behavior, treatment barriers and facilitators, attitudes towards different treatment options and access to treatment. Sociodemographic and clinical characteristics were also collected. The final sample comprised 276 individuals with OCD. The mean delay to seeking psychotherapeutic treatment was M = 5.15 years (SD = 6.88) and the mean delay to recognition of OCD was M = 5.58 years (SD = 7.16). Of those 211 who had ever received CBT, 49.5% reported that therapist-guided ERP had been performed at some point during treatment. Indicators of poor healthcare, such as longer delay to recognition or a larger number of treatments before receiving ERP were significantly associated with increased symptom severity. Moreover, a younger age was associated with a shorter delay to recognition of OCD. Taboo thoughts (60.9%) and checking (52.9%) were the most commonly reported symptom dimensions, and individuals with current taboo thoughts were significantly more likely to be treated with CBT. Educational websites were identified as the most important facilitators in recognizing OCD and providing information on effective treatment options. Lack of knowledge about treatment options was reported as the most common barrier to seeking/receiving ERP-based treatment. Delays to the recognition of OCD and to seeking help still exceed 5 years on average, but were reduced in younger individuals, potentially reflecting increased mental health literacy. Although our sample may not be fully representative, our results fill the gap between epidemiological surveys and previous studies in outpatients. Options for improving the care situation are discussed.

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

The proneness to minor errors and slips in everyday life as assessed by the Cognitive Failures Questionnaire (CFQ) constitutes a trait characteristic and is reflected in stable features of brain structure and function. It is unclear, however, how dynamic interactions of large-scale brain networks contribute to this disposition. To address this question, we performed a high model order independent component analysis (ICA) with subsequent dual regression on resting-state fMRI data from 71 subjects to extract temporal time courses describing the dynamics of 17 resting-state networks (RSN). Dynamic network interactions between all 17 RSN were assessed by linear correlations between networks’ time courses. On this basis, we investigated the relationship between subject-level RSN interactions and the susceptibility to everyday cognitive failure. We found that CFQ scores were significantly correlated with the interplay of the cingulo-opercular network (CON) and a posterior parietal network which unifies clusters in the posterior cingulate, precuneus, intraparietal lobules and middle temporal regions. Specifically, a higher positive functional connectivity between these two RSN was indicative of higher proneness to cognitive failure. Both the CON and posterior parietal network are implicated in cognitive functions, such as tonic alertness and executive control. Results indicate that proper checks and balances between the two networks are needed to protect against cognitive failure. Furthermore, we demonstrate that the study of temporal network dynamics in the resting state is a feasible tool to investigate individual differences in cognitive ability and performance. •Functional interactions between ICA-based resting-state networks are investigated.•We examine these interactions' relevance for proneness to everyday cognitive failure.•Key resting-state networks and patterns of network interaction are replicated.•An anterior x posterior cognition network interaction relates to cognitive failure.•A new promising individual differences approach to resting-state fMRI is presented.

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.