Risk For Obsessive-compulsive Disorder Research Articles

Association of rs11081062 polymorphism of DLGAP1 gene and levels of SLC1A1 protein with obsessive-compulsive disorder

Glutamate is an important neurotransmitter known to be effective in obsessive-compulsive disorder (OCD). The aim of this study is to investigate the relationship between the DLGAP1 gene encoding the scaffold protein of ionotropic glutamate receptors and the SLC1A1 gene encoding the glutamate transporter protein with OCD. Study groups consisted of 95 patients with OCD and 100 healthy controls. The severity of OCD in the patient group was determined by using the Y-BOCS. Single nucleotide polymorphisms of rs11081062 (C/T) in DLGAP1 and rs587777696 (C/T) in SLC1A1 were analyzed by real-time PCR. Levels of SLC1A1 protein were determined by ELISA. A significant difference was found between genotype distributions of rs11081062 in DLGAP1 in study groups (p < 0.001). No significant association was found rs587777696 in SLC1A1 in OCD patients and controls. SLC1A1 protein levels were found to be lower in OCD patients compared to controls (p = 0.005). According to OCD risk estimates for genotypes distributions of rs11081062 in DLGAP1, having CT + TT genotypes was associated with the occurrence of sexual and religious obsessions and counting compulsions (p = 0.038, OR = 2.98; p = 0.033, OR = 3.43; p = 0.035, OR = 2.66, respectively). CT genotype in DLGAP1 rs11081062 polymorphism was found to increase the risk of OCD in the female gender (p = 0.042, OR = 3.01). This study suggests that rs11081062 in DLGAP1 may be associated with OCD and that SLC1A1 protein levels may be involved in the occurrence of OCD. We believe that our research can contribute to the understanding of the importance of glutamate in OCD.

Epilepsy and psychiatric comorbidities: A bidirectional mendelian randomization study

Study objectivesPsychiatric comorbidities are relatively common among patients with epilepsy; however, the underlying mechanisms of this association remain largely unknown. The objective of this Mendelian randomization (MR) study was to analyze the genetic correlations and causality underlying these reciprocal associations. MethodsSingle-nucleotide polymorphisms associated with epilepsy (29,677 controls and 15,212 cases) and seven psychiatric comorbidities (485,436 controls and 269,495 cases) were identified from genome-wide association studies. Causal significance was estimated using inverse variance weighting. Sensitivity analyses included the weighted median, MR-Egger, and MR-PRESSO. The psychiatric comorbidities analyzed in this study included attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and anorexia nervosa. ResultsBoth forward and reverse genetic associations were observed for the selected psychiatric disorders. Notably, ADHD was significantly associated with an increased risk of generalized epilepsy (odds ratio [OR], 1.09; 95 % confidence interval [CI], 1.01–1.18; p = 0.013). However, MR-PRESSO detected the existence of pleiotropy (p = 0.001). Additionally, focal epilepsy was significantly associated with a higher risk of OCD (OR, 1.44; 95 % CI, 1.08–1.92; p = 0.013), and all sensitivity tests yielded favorably nonsignificant results. There was no significant genetic association between epilepsy and other examined psychiatric disorders. However, due to the detection of pleiotropy by MR-Egger and considerations related to the threshold for genetic instruments, a cautious approach is warranted in interpreting some of the results. ConclusionsThis study revealed significant genetic causality between focal epilepsy and OCD, as well as between ADHD and generalized epilepsy. However, no casual significance was observed with other psychiatric comorbidities examined. Considering the inherent limitations of MR studies, further research is warranted to definitively clarify these genetic causal associations.

A Family Genetic Study of Obsessive Compulsive Disorder in Youth

Objective: To use a family genetic study to evaluate familial risk of obsessive compulsive disorder (OCD) and common comorbid illnesses in first-degree relatives of pediatric-onset probands with primary OCD. Method: One hundred and thirty youth with OCD and their 133 siblings and 241 parents and 49 pediatric controls were directly evaluated along multiple domains including psychopathology using structured diagnostic interviews and clinical corroboration. Results: Rates of anxiety, mood, disruptive behavior, and tic disorders were markedly elevated in the probands while rates in siblings were elevated at rates between the probands and controls. Twenty six percent of first-degree relatives had clinical OCD, 9% had chronic tics or Tourette’s disorder, and 21% met criteria for ADHD. Conclusion: Rates of familial transmission of OCD and common comorbid illnesses were significantly higher in our pediatric-onset probands than rates reported in the literature in relatives of those with adult-onset OCD.

Association between HOTAIR genetic variants and risk of obsessive-compulsive disorder

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA with important roles in regulation of autophagy, neurite growth and morphogenesis. Polymorphisms within this gene have been associated with some neuropsychiatric conditions. In the current case-control study, we investigated associations between obsessive-compulsive disorder (OCD) and four single nucleotide polymorphism within this gene, namely rs12826786, rs4759314, rs1899663 and rs920778. There was significant difference in genotype distribution of rs920778 between OCD patients and normal controls (P value = 0.01). rs920778 was associated with risk of OCD in co-dominant model (TT versus CC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 0.66 (0.49–0.88), P value = 0.005 and OR (95 % CI) = 0.63 (0.44–0.91), P value = 0.014, respectively). This SNP was associated with OCD in dominant model (TT+TC versus CC) only in un-adjusted analysis (OR (95 % CI) = 0.52 (0.31–0.88), P value = 0.015). Finally, this SNP was associated with OCD in over-dominant model (CC+TT versus TC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 2.38 (1.33–4.25), P value = 0.003 and OR (95 % CI) = 2.78 (1.31–5.89), P value = 0.008, respectively). The current study shows possible impact of rs920778 on risk of OCD in Iranian population.

A family study assessing P300 as a probable electrophysiological endophenotype in obsessive-compulsive disorder

Objectives: Endophenotype models of disease would help to clarify both diagnostic classification and etiological understanding of obsessive-compulsive disorder (OCD). The objective of the study is to investigate electrophysiological endophenotypes in OCD. Material and Methods: We recorded P300 on an auditory oddball paradigm for 20 patients with OCD, their 20 first-degree relatives (FDRs), and 20 normal controls (matched with patients). Patients were assessed on the Yale-Brown Obsessive-Compulsive Scale, Hamilton Rating Scale for Anxiety, and Hamilton Rating Scale for Depression. Results: Both patients and FDRs had significantly shorter P300 latencies as compared to normal controls in all regions assessed (P &lt; 0.01). Significantly smaller centro-parietal (P &lt; 0.01) P300 amplitude on auditory oddball paradigm was found in patients and FDRs as compared to normal controls. Conclusion: Shorter P300 latency representing increased processing speed and smaller P300 amplitude reflective of dysfunctional response inhibition are suggested to mediate genetic risk for OCD and proposed as possible electrophysiological endophenotypes for OCD.

Interactions between genetic risk for 21 neurodevelopmental and psychiatric disorders and sport activity on youth mental health

Childhood is a sensitive period where behavioral disturbances, determined by genetics and environmental factors including sport activity, may emerge and impact risk of mental illness in adulthood. We aimed to determine if participation in sports can mitigate genetic risk for neurodevelopmental and psychiatric disorders in youth. We analyzed 4975 unrelated European youth (ages 9–10) from the Adolescent Brain Cognitive Development Study. Our outcomes were eight Child Behavior Checklist (CBCL) scores, measured annually. Polygenic risk scores (PRSs) were calculated for 21 disorders, and sport frequency and type were summarized. PRSs and sport variables were tested for main effects and interactions against CBCL outcomes using linear models. Cross-sectionally, PRSs for attention-deficit/hyperactivity disorder and major depressive disorder were associated with increases in multiple CBCL outcomes. Participation in non-contact or team sports, as well as more frequent sport participation reduced all cross-sectional CBCL outcomes, whereas involvement in contact sports increased attention problems and rule-breaking behavior. Interactions revealed that more frequent exercise was significantly associated with less rule breaking behavior in individuals with high genetic risk for obsessive compulsive disorder. Associations with longitudinal CBCL outcomes demonstrated weaker effects. We highlight the importance of genetic context when considering sports as an intervention for early life behavioural problems.

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods. Genetic analysis revealed severely damaging mutations in genes associated with OCD risk in humans. Brain imaging showed that monkeys with SMBs had larger gray matter (GM) volumes in the left caudate nucleus and lower fractional anisotropy of the corpus callosum. The GM volume of the left caudate nucleus correlated positively with the daily duration of SMBs. Notably, exposure to a stressor (human presence) significantly increased SMBs. In addition, fluoxetine, a serotonergic medication commonly used for OCD, decreased SMBs in these monkeys. These findings provide a novel foundation for developing better understanding and treatment of OCD.

Covid-19 &amp; Obsessive Compulsive Disorder – Clinical Intricacies

The globe-gripping pandemic of COVID-19 in 2020 compelled us to impose quarantines and lockdowns in many countries to curb the spread of this highly infectious disease, as well as, to follow safety guidelines like frequent handwashing, wearing masks or social distancing prescribed by the Center for Disease Control (CDC) for its prevention. The deadly virus has many mental health implications as well, which included depression, anxiety, and even obsessive-compulsive disorder (OCD). In fact, the preventive safety guidelines promoted behaviors resembled the acts observed in the individuals with OCD, e.g., contamination fear, related obsessions and compulsions worsened as a consequence. The fear of COVID-19 and increased stress levels contributed to increasing the risk of OCD among individuals. Children, elderly, youth, women during menstruation, pregnant women or health care workers were observed to be most vulnerable and at risk for developing OCD symptoms. The health belief model, the Stress Diathesis model and other social and environmental factors explained the theoretical rationale behind the development of related symptomology among individuals since the beginning of the COVID-19 pandemic. Intervention techniques like CBT, supportive therapy or psychoeducation can help the at-risk as well as the affected individuals. Finally, some limitations and directions of future researches have been proposed.

Exploring the Complex Associations Between Prenatal and Early-Life Infections and Obsessive-Compulsive and Tic-Related Disorders

An association between rheumatic fever and chorea was first posited at the beginning of the 19th century, but it was not until the mid–19th century that these observations crystalized into a widely accepted understanding that rheumatism caused Sydenham chorea ( 1 Martino D. Tanner A. Defazio G. Church A.J. Bhatia K.P. Giovannoni G. Dale R.C. Tracing Sydenham’s chorea: Historical documents from a British paediatric hospital. Arch Dis Child. 2005; 90: 507-511 Crossref PubMed Scopus (13) Google Scholar ). Advances in diagnostic methods, including the use of the stethoscope to detect cardiac manifestations of rheumatic fever, partially explain this discovery. However, perhaps an even more significant factor was the gradual shift during this period in the locus of medical care from the home to specialized centers, such as children’s hospitals, which led to case-based registries ( 1 Martino D. Tanner A. Defazio G. Church A.J. Bhatia K.P. Giovannoni G. Dale R.C. Tracing Sydenham’s chorea: Historical documents from a British paediatric hospital. Arch Dis Child. 2005; 90: 507-511 Crossref PubMed Scopus (13) Google Scholar ). It was from examination of these registries that British researchers were initially able to show a temporal relationship between seasonal spikes in rheumatic fever and chorea in children. SEE CORRESPONDING ARTICLE ON PAGE 1023 SEE CORRESPONDING ARTICLE ON PAGE 1023 Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders: A Nationwide, Sibling-Controlled StudyBiological PsychiatryVol. 93Issue 11PreviewPostinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD). Full-Text PDF Open Access

Shared genetic loci and causal relations between schizophrenia and obsessive-compulsive disorder

Based on the clinical overlap between schizophrenia (SCZ) and obsessive-compulsive disorder (OCD), both disorders may share neurobiological substrates. In this study, we first analyzed recent large genome-wide associations studies (GWAS) on SCZ (n = 53,386, Psychiatric Genomics Consortium Wave 3) and OCD (n = 2688, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS)) using a conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants of European descent. Using a variety of biological resources, we functionally characterized the identified genomic loci. Then we used two-sample Mendelian randomization (MR) to estimate the bidirectional causal association between SCZ and OCD. Results showed that there is a positive genetic correlation between SCZ and OCD (rg = 0.36, P = 0.02). We identified that one genetic locus (lead SNP rs5757717 in an intergenic region at CACNA1I) was jointly associated with SCZ and OCD (conjFDR = 2.12 × 10−2). Mendelian randomization results showed that variants associated with increased risk for SCZ also increased the risk of OCD. This study broadens our understanding of the genetic architectures underpinning SCZ and OCD and suggests that the same molecular genetic processes may be responsible for shared pathophysiological and clinical characteristics between the two disorders.

The infected and the affected: A longitudinal study of the impact of the COVID-19 pandemic on schoolchildren in Florida.

To identify risk factors associated with symptoms of anxiety, depression, and obsessive-compulsive disorder (OCD) among children during the 1st year of the COVID-19 pandemic. A longitudinal study with three cross-sectional timepoints [April 2020 (n = 273), October 2020 (n = 180), and April 2021 (n = 116)] was conducted at a K-12 public school in Florida. Infection and sero-positivity for SARS-CoV-2 was determined by molecular and serologic approaches. Adjusted odds ratios using mixed effect logistic regression models for symptom-derived indicators of anxiety, depression, and OCD in children in April 2021 are presented; past infection and seropositivity were included in the models. The prevalence of anxiety, depression, or OCD moved from 47.1, to 57.2, to 42.2% across the three timepoints during the study. By endline of the study, in April 2021, non-white children were at higher risk for depression and OCD. Risk for anxiety, depression, and OCD was associated with students who lost a family member due to COVID-19 and who were identified as at-risk in previous timepoints. Rates of SARS-CoV-2 infection and seropositivity were low and not statistically associated with assessed outcomes. In situations like the COVID-19 pandemic, targeted mental health interventions and screenings are needed in children and adolescents, especially among minority children.

Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system: a national study.

To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

The COVID-19 pandemic and obsessive-compulsive disorder: a systematic review of comparisons between males and females.

Coronavirus disease, one of the most disastrous epidemics, has caused a worldwide crisis, and the containment measures applied to decelerate the progression of the pandemic can increase the risk of obsessive-compulsive disorder (OCD). Identifying vulnerable groups in this area can lead us to better resource expenditure, and therefore, this systematic review aims to make a comparison between males and females to determine which of the two groups was most affected by the COVID-19 pandemic regarding OCD. Also, a meta-analysis was designed to investigate the prevalence of OCD during the COVID-19 pandemic. A comprehensive search was conducted among three databases (Medline, Scopus, Web of Science) until August 2021 which resulted in 197 articles, and 24 articles met our inclusion criteria. Overall, more than half of the articles stated the role of gender in OCD during the COVID-19 pandemic. Several articles emphasized the role of the female gender, and some others the role of the male gender. The meta-analysis revealed a 41.2% overall prevalence of OCD during the COVID pandemic and 47.1% and 39.1% OCD prevalence for female and male genders respectively. However, the difference between the two genders was not statistically significant. Generally, it seems that females are at greater risk of OCD during the COVID-19 pandemic. In the following groups, the female gender may have acted as a risk factor: under-18 years students, hospital staff, and the studies in the Middle East. In none of the categories, male gender was clearly identified as a risk factor.

Association between ANRIL polymorphisms and risk of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disorder in which genetic factors participate. ANRIL is an example of long non-coding RNAs with crucial roles in the pathoetiology of multifactorial disorders, including neuropsychiatric conditions. We appraised association between rs1333045, rs1333048, rs10757278 and rs4977574 polymorphisms and OCD in Iranian population. There were no remarkable differences in allele and genotype distribution of rs1333045, rs1333048, rs4977574, and rs10757278 between OCD Patients and normal controls. However, the CCGG haplotype (equivalent to rs1333045, rs1333048, rs4977574 and rs10757278, respectively) has been shown to decrease risk of OCD (OR (95% CI) = 0.57 (0.39–0.85), P value-0.006 and FDR q-value = 0.041). On the other hand, TCGA haplotype has been found as a risk haplotype for OCD (OR (95% CI) = 5.17 (1.44–18.55), P value = 0.005 and FDR q-value = 0.041). In brief, the current study indicates association between two ANRIL haplotypes and risk of OCD in Iranian people.

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

Background: Recent studies report an important—and previously underestimated—role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. Method: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. Results: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). Conclusions: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders: A Nationwide, Sibling-Controlled Study

BackgroundPostinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD). MethodsIndividuals exposed to any prenatal maternal infection (n = 16,743) and early childhood infection (n = 264,346) were identified from a population-based birth cohort consisting of 2,949,080 singletons born in Sweden between 1973 and 2003 and were followed through 2013. Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Sibling analyses were performed to control for familial confounding. ResultsAt the population level, and after adjusting for parental psychiatric history and autoimmune diseases, a significantly increased risk of OCD and TS/CTD was found in individuals exposed to prenatal maternal (but not paternal) infections (OCD: HR, 1.33; 95% CI, 1.12–1.57; TS/CTD: HR, 1.60; 95% CI, 1.23–2.09) and early childhood infections (OCD: HR, 1.19; 95% CI, 1.14–1.25; TS/CTD: HR, 1.34; 95% CI, 1.24–1.44). However, these associations were no longer significant in the sibling analyses. ConclusionsThe results do not support the hypothesis that prenatal maternal or early-life infections play a direct causal role in the etiology of either OCD or TS/CTD. Instead, familial factors (e.g., genetic pleiotropy) may explain both the propensity to infections and the liability to OCD and TS/CTD.

Shared genetic basis between reproductive behaviors and anxiety-related disorders.

Reproductive behaviors are associated with risks for psychiatric disorders. Reproductive phenotypes are moderately heritable and have genetic overlaps with risks for psychiatric disorders. However, the genetic and causal relationships between anxiety-related disorders or specific anxiety disorders and reproductive phenotypes remain unknown. We utilized large-scale genome-wide association study (GWAS) results (n = 9537-542,901) for five reproductive phenotypes [age at menarche, age at first sexual intercourse (AFS), age at first birth (AFB), number of children ever born (NEB), and age at menopause] and five anxiety-related disorders [panic disorder, anxiety disorders from the ANGST and the UK biobank (UKBB), posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD)]. To assess genetic correlations and causal associations, linkage disequilibrium score regression and Mendelian randomization analyses, respectively, were performed. We found that AFS and AFB were negatively correlated with anxiety disorders ANGST (AFS: rg ± SE = -0.28 ± 0.08, p = 6.00 × 10-4; AFB: -0.45 ± 0.11, p = 3.26 × 10-5), anxiety disorders UKBB (AFS: -0.18 ± 0.03, p = 9.64 × 10-9; AFB; -0.25 ± 0.03, p = 2.90 × 10-13) and PTSD (AFS: -0.42 ± 0.12, p = 4.00 × 10-4; AFB: -0.44 ± 0.12, p = 2.00 × 10-4) and positively correlated with OCD (AFS: 0.25 ± 0.05, p = 2.46 × 10-6; AFB: 0.25 ± 0.05, p = 3.92 × 10-7). Conversely, NEB was negatively correlated with OCD (-0.28 ± 0.08, p = 6.00 × 10-4). We revealed bidirectional effects between earlier AFS and AFB and anxiety disorders (odds ratios: ORearlier AFS→Anxiety = 1.64, p = 2.27 × 10-8; ORearlier AFB→Anxiety = 1.15, p = 2.28 × 10-3; ORAnxiety→earlier AFS = 1.02, p = 6.62 × 10-8; ORAnxiety→earlier AFB = 1.08, p = 1.60 × 10-4). In contrast, we observed unidirectional effects of later AFS and AFB on OCD (ORlater AFS→OCD = 2.18, p = 2.16 × 10-6; ORlater AFB→OCD = 1.22, p = 0.016). We suggest that those who have earlier sexual debut and childbirth are prone to risk for anxiety disorders and vice versa, while those who have later sexual debut and childbirth are genetically prone to risk for OCD. Our findings further support revising the diagnostic criteria (DSM-5) such that OCD is independent from anxiety disorders.

Epigenome-wide DNA methylation in obsessive-compulsive disorder

In adult patients with obsessive-compulsive disorder (OCD), altered DNA methylation has been discerned in several candidate genes, while DNA methylation on an epigenome-wide level has been investigated in only one Chinese study so far. Here, an epigenome-wide association study (EWAS) was performed in a sample of 76 OCD patients of European ancestry (37 women, age ± SD: 33.51 ± 10.92 years) and 76 sex- and age-matched healthy controls for the first time using the Illumina MethylationEPIC BeadChip. After quality control, nine epigenome-wide significant quantitative trait methylation sites (QTMs) and 21 suggestive hits were discerned in the final sample of 68 patients and 68 controls. The top hit (cg24159721) and four other significant QTMs (cg11894324, cg01070250, cg11330075, cg15174812) map to the region of the microRNA 12136 gene (MIR12136). Two additional significant CpG sites (cg05740793, cg20450977) are located in the flanking region of the MT-RNR2 (humanin) like 8 gene (MT-RNRL8), while two further QTMs (cg16267121, cg15890734) map to the regions of the MT-RNR2 (humanin) like 3 (MT-RNRL3) and MT-RNR2 (humanin) like 2 (MT-RNRL2) genes. Provided replication of the present findings in larger samples, the identified QTMs might provide more biological insight into the pathogenesis of OCD and thereby could in the future serve as peripheral epigenetic markers of OCD risk with the potential to inform targeted preventive and therapeutic efforts.

Specific Aspects of Eye Movement Reactions as Markers of Cognitive Control Disorders in Patients with Obsessive-Compulsive Disorder (Review).

Multiple studies in patients with obsessive-compulsive disorder (OCD) became the basis for revealing selective attention, inhibitory control, and working memory impairments, which correlates with an imbalance in the activity of the cortico-striatal-thalamic-cortical circuit associated with maintenance of cognitive control functions. Patients with OCD often demonstrate changes in the parameters of target-oriented eye movement reactions being a consequence of a possible impairment of the cognitive control neurophysiological framework. This review summarizes and analyzes data on cognitive control disorders in OCD obtained with eye movement recording techniques. It was established that the most often used are smooth pursuit eye movements tasks, memory-guided saccades, and anti-saccadic tasks. Data on smooth pursuit eye movements tasks and memory-guided saccades are contradictory, although they partially confirm selective attention and working memory impairment. Most studies on the anti-saccadic task identified impaired inhibitory control in patients with OCD. Similar disorders in form of increased latency and higher error rate in anti-saccades were also noted in the patients' first-degree relatives, which allows considering such disorders as manifestations of the endophenotype associated with the underlying risk of OCD. Future confirmation of these results in experiments using complex anti-saccadic tasks with images of various modalities (taking into account the increased anxiety in patients with OCD as the disorder basis) might contribute to validation of the OCD-specific markers.

Time-Varying and Time-Invariant Dimensions in Intolerance of Uncertainty: Specificity in the Prediction of Obsessive-Compulsive Symptoms

Intolerance of uncertainty (IU) is the tendency to respond negatively toward uncertain situations. IU consists of a Prospective factor (desire for predictability) and an Inhibitory factor (uncertainty paralysis) and is central to theoretical approaches to obsessive-compulsive disorder (OCD). However, time-invariant (TI) and time-varying (TV) components of IU and their association with OCD symptoms are not yet understood. The present study examined the association between TI and TV components of IU and OCD symptoms in community adults (N = 1,280) over a 5-month period. Latent variable models were fit to the data to examine the relative impact of TI and TV components of IU on OCD symptoms. As a test of specificity, models examining the association between TI and TV components of IU and depressive symptoms were also examined. The results showed that IU consists of significant TI and TV components, although the TI component accounted for most of the variance (76–84%) and was more strongly associated with OCD and depressive symptoms than the TV component. Furthermore, the TI component of IU was strongly associated with OCD symptoms when controlling for depressive symptoms, and the TI component of IU was strongly associated with depressive symptoms when controlling for OCD symptoms. A consistent pattern was observed for both Prospective and Inhibitory IU factors, with stable TI components demonstrating stronger relations with OCD and depressive symptoms than TV components. These findings have implications for conceptualizing the TI component of IU as a risk for OCD and other emotional disorders.