Risk For Obsessive-compulsive Disorder Research Articles

BDNF gene and obsessive compulsive disorder risk, symptom dimensions and treatment response.

Genetic etiology of Obsessive Compulsive Disorder (OCD) has been investigated extensively, with mixed results across candidate gene studies. The dimensional subtypes of OCD are shown to better correlate with brain imaging endophenotypes and thus could potentially enhance the power of genetic association. In this study, we perform a case control analysis of association of a single nucleotide polymorphism rs6265(Val66Met) in Brain Derived Neurotrophic Factor gene, that has been previously implicated in a variety of psychiatric syndromes, and examine its association with symptom dimensions of OCD. Individuals diagnosed to have OCD (n=377) and controls (n=449) of South Indian origin were genotyped for polymorphism rs6265 (196G/A, Val66Met). Detailed phenotypic assessment of the cases were carried out in the cases using structured instruments. The genotypic association was tested for clinical variables such as age of onset, gender, family history, co-morbidity, treatment response, and factor analyzed OCD symptom dimensions. The allele 'A' frequency was found to be significantly higher in the controls, as compared to cases suggesting a protective effect. The contamination/washing symptom dimension score was significantly lower in carriers of 'A' allele which remained significant even after testing for confounding effects on linear regression. Our results support findings from previous studies on a possible protective effect of the 'Met' allele at the Val66Met locus in OCD. Its association with lower scores on the contamination/washing dimension is a novel finding of this study.

The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: a new approach

Aim: Toxoplasma gondii may play a role in the development of psychiatric diseases by affecting the brain. The purpose of this study was to examine the relation between serum toxoplasma IgG positivity and obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) in children and adolescents.Method: Sixty patients diagnosed with OCD and 60 patients with GAD presenting to the pediatric psychiatry clinic, together with 60 control group subjects with no psychiatric diagnosis, were included in the study. The patients were administered the State–Trait Anxiety Inventory for Children and the Children’s Yale–Brown Obsessive Compulsive Scale. Serum toxoplasma IgG levels were determined from blood specimens collected from the study and control groups. The results were then compared using statistical methods.Results: State and trait anxiety levels were significantly higher in the OCD and GAD patients than in the control group (p = .0001/.0001). Serum toxoplasma IgG levels were positive in 21 (35%) of the OCD patients, 19 (31.7%) of the GAD patients and 6 (10%) of the control group. A significant relation was determined between IgG positivity and GAD (p = .003). IgG-positive individuals were determined to have a 4.171-fold greater risk of GAD compared to those without positivity (4.171[1.529–11.378]) (p = .005). A significant relation was also determined between IgG positivity and OCD (p = .001). IgG-positive individuals were determined to have a 4.846-fold greater risk of OCD compared to those without positivity (4.846[1.789–13.126]) (p = .002).Conclusion: This study shows that serum toxoplasma IgG positivity indicating previous toxoplasma infection increased the risk of GAD 4.171-fold and the risk of OCD 4.846-fold in children and adolescents. Further studies are now needed to investigate the relation between T. gondii infection and GAD/OCD and to determine the pathophysiology involved.

Situation Awareness in Obsessive Compulsive Disorder and Their Relatives: an Endophenotype Study.

It has been theorized that endophenotype models will help to understand the etiology of heterogeneous brain disorders such as obsessive-compulsive disorder (OCD). In this study, it was aimed to determine whether "situational awareness" impairments which can be defined as partially naturalistic working memory deficits, are an endofenotype for OCD. In this study, situational awareness (SA) task performances of 67 OCD patients, 50 their unaffected first-degree relatives, and 41 healthy controls who matched with regard to sex, age and years of education were measured to investigate endophenotypes in OCD. For this purpose, a visuospatial working memory test was used. As a result, the relatives showed a task performance between patients with OCD and control group in both SA1 and SA2 tasks. Patients with OCD performed significantly worse than control group on SA1 single and dual task. On the other hand, there were no significant differences between relatives and patients of any SA assessment. These results indicated that poor situational awareness may be a candidate endophenotype for OCD. Early perceptual dysfunctions such as poor performance on SA1 task can mediate the genetic risk for OCD.

Can Childhood Infections Trigger Mental Disorders?

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessCan Childhood Infections Trigger Mental Disorders?JoAnn BlakeJoAnn BlakeSearch for more papers by this authorPublished Online:17 Aug 2017https://doi.org/10.1176/appi.pn.2017.8b13AbstractUnderstanding the role post-infectious autoimmunity plays in a large spectrum of psychiatric symptoms could lead to new avenues for the treatment and prevention of childhood mental illness.The latest and largest-scale study to test the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) hypothesis supports the curious role of infections in the development of mental illness.Strep infection such as strep throat or scarlet fever has been linked with obsessive-compulsive disorder (OCD) and tic disorders, a controversial concept first defined by Susan Swedo, M.D., then a pediatrician-researcher at the National Institute of Mental Health (NIMH). Dramatic symptoms appear suddenly after the infection, and may include motor or vocal tics, obsessions, compulsions, and anxiety attacks. Sonja Orlovska, M.D., says one of the main findings from the recent Danish research study testing the PANDAS hypothesis is “the connection between somatic and mental illness.”Almost 20 years ago, Swedo and colleagues published a study about the first PANDAS cases they identified, “Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases” (American Journal of Psychiatry, 1998). Since then, numerous research groups have tried to prove or disprove the hypothesis. The 2017 Danish study, “Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study,” published online in JAMA Psychiatry May 24, shows that children with preceding strep throat infections did indeed have an elevated risk of mental disorders, particularly OCD and tic disorders. However, the study also found non-streptococcal throat infection to be associated with increased risks, though to a lesser degree. This finding may support a more recent broader concept called pediatric acute-onset neuropsychiatric syndrome (PANS).“Our study contradicts the PANDAS hypothesis to some extent,” wrote first author and co-researcher Sonja Orlovska, M.D., affiliated with the Mental Health Centre Copenhagen and the University of Copenhagen, Denmark, in an email to Psychiatric News. “Still, the risk of OCD remained highest after a step versus non-strep throat infection, pointing to a specific association between strep infection and OCD, in line with PANDAS.”Swedo, now director of the Pediatrics and Developmental Neuroscience Branch at NIMH, called the Danish study an important addition to the growing body of PANS/PANDAS literature. “Their finding of increased rates of any mental disorder following strep infection suggests that post-infectious autoimmunity may play a role in a large spectrum of psychiatric symptoms, which could lead to new avenues for treatment and prevention of childhood mental illness,” she said in a statement to Psychiatric News.The Danish researchers concluded that their results may favor the essential elements of PANS, because it offers an alternative to PANDAS with wider diagnostic criteria and without the restriction of streptococcal infection. Data Specifics From the Danish Study This PANS/PANDAS population-based cohort study used data from 1,067,743 individuals under 18 years of age in the nationwide Danish registers between January 1, 1996, and December 31, 2013, with up to 17 years of follow-up. The Danish National Health Service Register provided information on individuals with the registration of a streptococcal test. Data analysis was conducted from January 1, 2016, to February 28, 2017.Of the children included in the study (519,821 girls and 547,922 boys), 638,265 received a streptococcal test, 349,982 of whom had positive test results at least once.Children with positive streptococcal test results had an increased risk of any mental disorder (n = 15,408; IRR, 1.18), particularly of OCD (n = 556; IRR, 1.51) and tic disorders (n = 993; IRR, 1.35), compared with individuals who had never been tested for streptococcal infection, according the study. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a non-streptococcal infection. Nonetheless, individuals with a non-streptococcal throat infection also had an increased risk of any mental disorder (n = 11,315; IRR, 1.08), OCD (n = 316; IRR, 1.28), and tic disorders (n = 662; IRR, 1.25).The study was supported in part by grants from the Lundbeck Foundation and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. ■An abstract of “Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study” can be accessed here. “Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases” is available here. ISSUES NewArchived

Parental age and the risk of obsessive compulsive disorder and Tourette syndrome / chronic tic disorder in a nationwide population-based sample

ObjectivesAdvancing paternal age has been associated with several neuropsychiatric disorders in children. However, there is limited understanding of this association with obsessive compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT) with inconsistent findings. We examined the association between parental age and offspring OCD and TS/CT. MethodsThis nested case-control study used the Finnish Hospital Discharge Register (FHDR) to identify 1358 individuals with OCD and 1195 with TS/CT, born from 1991 to 2009 and diagnosed by 2010. Each case was matched with four controls from the Finnish Population Register (FPR), without diagnoses of OCD, TS/CT or severe or profound mental retardation. Conditional logistic regression was used to examine the association between parental age and OCD, TS/CT. ResultsA trend of increasing odds was seen with advancing maternal age. In the final model, offspring of mothers aged 35–39 years had a 1.3-fold increased odd (OR = 1,31, 95% confidence interval (95% CI:1.03–1.66)) of OCD compared with maternal aged 25–29 years. Offspring of fathers younger than 20 years had increased odds of TS/CT in the unadjusted analysis (OR = 2.43, 95% CI: 1.27–4.56). LimitationsThe study limitations included using hospital diagnoses to identify cases, with limited diagnostic validity, and the possible over representation of moderate to severe cases. ConclusionsThe lack of association between advancing paternal age and OCD is in contrast with schizophrenia, despite sharing demographic characteristics and possible shared neuropathology. Furthermore, these differences suggest different etiological pathways among TS/CT, autism spectrum disorder (ASD) and attention deficit/hyperactive disorder (ADHD), despite their frequently comorbid existence.

308. Decision-Making under Risk in Obsessive-Compulsive Disorder and Anxiety: A Cumulative Prospect Theory Model

308. Decision-Making under Risk in Obsessive-Compulsive Disorder and Anxiety: A Cumulative Prospect Theory Model

Psychiatric disorders in a cohort of individuals with Prader–Willi syndrome

BackgroundPsychiatric manifestations in Prader–Willi Syndrome (PWS) are common and often are the most debilitating problem in these individuals. We present an epidemiological nation-wide survey of psychiatric diagnoses in the PWS population, based on full-range psychiatric interviews. MethodsWe studied the distribution of psychiatric diagnoses (as opposed to a symptom-based approach) in the Israel national cohort of adolescents and adults with PWS. There was a total of 53 (32 males) ages 12 years and older. All individuals and their caretakers were interviewed using standardized psychiatric questionnaires. Demographic and clinical variables, Clinical Global Impression (CGI) score, IQ, severity of hyperphagia and quality of life (QOL) were also assessed and correlations with NPD (number of psychiatric diagnoses) calculated. ResultsAn overwhelming majority (89%) of the study participants had at least one psychiatric diagnosis. The most common were disruptive behavior disorders (DBD) (68%), obsessive compulsive disorder (OCD) (45%) and skin picking (35%). Individuals with DBD were at increased risk for OCD and skin picking. Psychotic disorders were found in 11%. NPD had a significant negative influence on QOL. There was no correlation between NPD and BMI, IQ, hyperphagia severity, hormonal profile or genetic subtypes. ConclusionsPsychiatric diagnoses are very frequent in PWS and strongly influence QOL. Furthermore, characterizing the profile of psychiatric comorbidity in PWS is crucial for planning effective interventions. Precise behavioral phenotyping in PWS in combination with a well-defined genetic etiology may aid biological research linking biological correlates to behavior.

Register-based study of the incidence, comorbidities and demographics of obsessive-compulsive disorder in specialist healthcare

BackgroundIncidence of obsessive-compulsive disorder (OCD) has been suspected to increase but nationwide epidemiological studies are limited. This study aims to examine sex-specific incidence time trends and characterize psychiatric and neurodevelopmental comorbidities and sociodemographic risk factors of OCD in specialist healthcare in Finland.MethodsA nationwide register-based study using data from four Finnish registers identified 3372 OCD cases and 13,372 matched controls (1:4). Cumulative incidence in subjects born between 1987 and 2001 was estimated at ages of 10, 15, 20 and 23 years. Conditional logistic regression was used to examine the sociodemographic factors.ResultsThe cumulative incidence of OCD was 0.4% by age 23. Incidence by age 15 among three cohorts increased from 12.4 to 23.7 /10000 live born males and 8.5 to 28.0 /10000 live born females. 73% of the sample had a comorbid condition. Males were significantly more comorbid with psychotic and developmental disorders; females were more comorbid with depressive and anxiety disorders (p <0.001). Higher maternal SES was associated with an increased risk of OCD (OR 1.4; 95% CI 1.1–1.6).ConclusionsThese findings suggest that incidence of treated OCD in specialist healthcare has increased. The reason may be increased awareness and rate of referrals but a true increase cannot be ruled out. Further research on risk factors of OCD is warranted.

Rare Synaptogenesis-Impairing Mutations in SLITRK5 Are Associated with Obsessive Compulsive Disorder.

Obsessive compulsive disorder (OCD) is substantially heritable, but few molecular genetic risk factors have been identified. Knockout mice lacking SLIT and NTRK-Like Family, Member 5 (SLITRK5) display OCD-like phenotypes including serotonin reuptake inhibitor-sensitive pathologic grooming, and corticostriatal dysfunction. Thus, mutations that impair SLITRK5 function may contribute to the genetic risk for OCD. We re-sequenced the protein-coding sequence of the human SLITRK5 gene (SLITRK5) in three hundred and seventy seven OCD subjects and compared rare non-synonymous mutations (RNMs) in that sample with similar mutations in the 1000 Genomes database. We also performed in silico assessments and in vitro functional synaptogenesis assays on the Slitrk5 mutations identified. We identified four RNM’s among these OCD subjects. There were no significant differences in the prevalence or in silico effects of rare non-synonymous mutations in the OCD sample versus controls. Direct functional testing of recombinant SLITRK5 proteins found that all mutations identified in OCD subjects impaired synaptogenic activity whereas none of the pseudo-matched mutations identified in 1000 Genomes controls had significant effects on SLITRK5 function (Fisher’s exact test P = 0.028). These results demonstrate that rare functional mutations in SLITRK5 contribute to the genetic risk for OCD in human populations. They also highlight the importance of biological characterization of allelic effects in understanding genotype-phenotype relationships as there were no statistical differences in overall prevalence or bioinformatically predicted effects of OCD case versus control mutations. Finally, these results converge with others to highlight the role of aberrant synaptic function in corticostriatal neurons in the pathophysiology of OCD.

M32 - Mitochondrial Genetic Risk In OCD And Related Subphenotypes

Background Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder that has strong genetic risk, but the precise factors remain to be identified. Mitochondria play crucial roles in neurons, such as Ca2+ regulation, redox signaling, development, synaptic plasticity, and apoptosis. The importance of mitochondria in neurons is evident from the reported comorbidity between mitochondrial diseases and neuropsychiatric symptomatology. Here we examined the role of nuclear-encoded oxidative phosphorylation related genes in OCD risk and its sub-phenotypes. Methods We selected 28 genes involved in oxidative phosphorylation or in oxidative stress, mitochondrial biogenesis, inflammation and apoptosis. A total of 59 SNPs were analyzed in 477 OCD subjects. Logistic regression was used for OCD risk analysis and linear regression was used to test association with the sub- phenotypes of interest. Given the complexity of the OCD phenotype, we also tested for association with symptom-defined subphenotypes based on YBOCS symptom dimension scores calculated using the YBOCS, in addition to age at onset and overall symptom severity. We used a permutation based test to examine the hypothesis that our set of mitochondrial genes, collectively, was associated with OCD risk. Results From case-control analysis, we observed nominally significant association for the SNPs rs4011457 in the NDUFS7 gene and OCD risk (N=856, P(uncorrected)= 0.004). Also, nominally significant evidence for association was observed for the SNP rs3820189 in the 5’of the MFN2 gene and YBOCS total score (N=346; P(uncorrected)= 0.002) and for the SNP rs4246944 in the PPIF gene and Sex/Religion factor (N=371; P(uncorrected)= 0.002). A permutation-based test of all 59 SNPs jointly showed significant association with OCD (P(perm)=0.003). Discussion To the best of our knowledge, this is the first study to show evidence that nuclear-encoded mitochondrial genes may influence OCD.

M33 - GENETIC VARIATION AND EPIGENETIC MODIFICATION OF SKA2: ASSOCIATIONS WITH OBSESSIVE-COMPULSIVE DISORDER DISEASE RISK AND SYMPTOM SEVERITY

Background Obsessive-Compulsive Disorder (OCD) has a strong genetic component, is highly comorbid with Major Depressive Disorder (MDD), and is often triggered by environmental stress. Epigenetic modifications are thought to play a significant role in complex psychiatric disorders and may impact the relationship between genes and the environment via the hypothalamic-pituitary-adrenal (HPA) axis. The SKA2 gene interacts with the glucocorticoid receptor, is implicated in mediating HPA axis function, but has yet to be examined in OCD. We hypothesized that genetic and epigenetic variation in SKA2 may play a role in OCD disease risk and symptom severity. Methods A sample of n=64 OCD patients, divided equally by presence/absence of comorbid MDD, and age and gender matched, were selected. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score was used to measure disease severity. Genotyping for the SKA2 rs7208505 marker was performed using the Taqman allele specific assay method and DNA methylation levels were quantified using bisulfite pyrosequencing. Methylation percentage was corrected for genotype using previously established methods. Genotypes for rs7208505 were compared to controls of European ancestry (n=365; 1000 Genomes Project Consortium) using Pearson’s chi-squared test. The relationship among the rs7208505 variant, methylation corrected, symptom severity, and MDD status was modeled using linear regression. Results The SKA2 rs7208505 genotype distributions significantly differed between OCD patients and controls (χ2=8.66, p=0.013). Genotypes were associated with symptom severity (p=0.011), in that patients with the CC genotype had lower Y-BOCS scores than the CT/TT genotypes. While OCD patients diagnosed with MDD had more severe Y-BOCS scores (p=0.023), neither genetic nor epigenetic variation of rs7208505 was associated with comorbid MDD status. Methylation corrected for genotype was not significant in the regression model (p>0.05). Discussion These results provide some evidence that SKA2 genetic variation may be associated with OCD risk and symptom severity. Methylation corrected for genotype was not associated with OCD symptom severity; however, patients with TT and CT genotypes had more severe Y-BOCS scores than the CC genotype carriers. Further work will include replication in larger samples and interrogating additional genetic and epigenetic variations in SKA2.

Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study.

Introduction:Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD.Methods:Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software.Results:The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein α-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein α-1-antitrypsin (APOA1) proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process.Conclusion:It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential requirements to confirm this preliminary evaluation.

Neuronal nitric oxide synthase polymorphisms in obsessive-compulsive disorder

Background: Obsessive-compulsive disorder (OCD) is a mental disease characterized by recurrent and intrusive thoughts and repetitive behaviours that negatively affect the quality-of-life of the patients. Recent studies have implicated the participation of neuronal nitric oxide in OCD pathogenesis as a neurotransmitter modulator.Aims: To identify whether variations in neuronal nitric oxide synthase (nNOS) genes may render individuals susceptible to OCD development.Methods: This study examined nNOS polymorphisms in 100 OCD patients and 121 unrelated healthy controls by polymerase chain reaction and restriction enzyme digestion methods.Results: nNOS 276 C + genotype incidence was significantly higher in OCD patients than controls and conferred a 2-fold increased risk for OCD. No significant differences were observed in frequencies of nNOS 84 genotypes between patients and controls.Conclusion: This study shows an association between nNOS gene polymorphism and OCD. Exact mechanisms by which nNOS gene variants contribute to OCD pathogenesis need to be further investigated.

Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder

Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding. To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses. This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016. Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference. Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register. Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events. A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.

Genome-wide DNA methylation analysis in obsessive-compulsive disorder patients.

Literatures have suggested that not only genetic but also environmental factors, interactively accounted for susceptibility of obsessive-compulsive disorder (OCD). DNA methylation may regulate expression of genes as the heritable epigenetic modification. The examination for genome-wide DNA methylation was performed on blood samples from 65 patients with OCD, as well as 96 healthy control subjects. The DNA methylation was examined at over 485,000 CpG sites using the Illumina Infinium Human Methylation450 BeadChip. As a result, 8,417 probes corresponding to 2,190 unique genes were found to be differentially methylated between OCD and healthy control subjects. Of those genes, 4,013 loci were located in CpG islands and 2,478 were in promoter regions. These included BCYRN1, BCOR, FGF13, HLA-DRB1, ARX, etc., which have previously been reported to be associated with OCD. Pathway analyses indicated that regulation of actin cytoskeleton, cell adhesion molecules (CAMs), actin binding, transcription regulator activity, and other pathways might be further associated with risk of OCD. Unsupervised clustering analysis of the top 3,000 most variable probes revealed two distinct groups with significantly more people with OCD in cluster one compared with controls (67.74% of cases v.s. 27.13% of controls, Chi-square = 26.011, df = 1, P = 3.41E-07). These results strongly suggested that differential DNA methylation might play an important role in etiology of OCD.

Metabolite- protein interaction (MPI) network analysis of obsessive- compulsive disorder (OCD) from reported metabolites

Obsessive-Compulsive Disorder (OCD) is a lifetime mental condition with the prevalence of 1-3% in general population. Molecular evaluation of OCD is prominent to understand the complex basis of underlying mechanisms. Here, by the application of MPI construction of significant changed metabolites in OCD patients, it is tried to obtain a preliminarily insight of related molecular interactions. These interactions are fundamental for cell processes and drug design. For this purpose, a number of ten OCD related metabolites were obtained from literature, by the use of PubMed and Google Scholar Resources. Then, the ten candidate metabolites were examined by the application of STITCH 4.0 Online Resource, for investigating the ten significant linked proteins with our query metabolites and the related BPs. Top ten scored interacting proteins with the query metabolites were retrieved and the action types were identified. Some of the protein partners were previously detected as potential polymorphisms in OCD etiology. The Regulation of hormone secretion and regulation of phosphorylation are the most significant (corrected p value< 0.05) related biological process of the ten investigated metabolites in the whole network. The result suggests that, insulin may be influenced significantly in OCD profile as it is significantly regulated by the six of our metabolites in the whole network. In fact, either metabolites or proteins changes may influence each other levels and promotes OCD risk. Thus, further systematic analysis is suggested for confirmation and introduction of new biomarkers.

Obsessional and Eating Disorder-related Intrusive Thoughts: Differences and Similarities Within and Between Individuals Vulnerable to OCD or to EDs.

Unwanted intrusive cognitions constitute the normal variant of clinically significant intrusive cognitions found in disorders such as obsessive-compulsive disorder (OCD) and eating disorders (EDs). This study investigates whether individuals who are vulnerable to OCD or EDs experience more intrusions than people with no vulnerability to these disorders, and it examines the consequences of obsessional (OITs) and eating disorder (EDITs) intrusions in the same individuals, taking into account their susceptibility to OCD, EDs or neither of the two. From a sample of 922 participants, three groups were formed: risk of OCD (n = 92), risk of EDs (n = 41) and a no-risk group (n = 100). EDITs were more frequent than OITs in the two risk groups. Within-group comparisons showed that in the OCD-risk group, the OIT had more negative consequences (interference, emotional distress, dysfunctional appraisals and neutralizing strategies) than the EDIT, whereas in the ED-risk group, the OIT and the EDIT instigated similar negative consequences. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Obsessive-compulsive adults with and without childhood ADHD symptoms.

Obsessive-compulsive disorder (OCD) and attention-deficit and hyperactivity disorder (ADHD) frequently coexist. To understand whether childhood ADHD can increase the risk of OCD in adulthood and whether it influences the phenomenology of OCD, we investigated the symptoms of ADHD during childhood in obsessive-compulsive adults who had never been diagnosed as ADHD. Adults with OCD (n=83) were given the Wender Utah Rating Scale (WURS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Barratt Impulsiveness Scale-11 (BIS-11), Hamilton Depression Rating Scale-17 (HDRS-17) and Beck Anxiety Inventory (BAI). The prevalence of childhood ADHD symptoms was 40.9% (n=34) and that of adult ADHD was 16.9% (n=14). Patients with childhood ADHD symptoms had an earlier onset of OCD, higher scores of the BAI and BIS-11. The scores of the Y-BOCS and HDRS-17 did not differ between those having and not having childhood ADHD symptoms. Childhood history of ADHD symptoms is common in adult OCD patients who have never been diagnosed as ADHD. Childhood ADHD symptoms are associated with an earlier age of OCD, more severe anxiety and higher impulsiveness. Even remitted ADHD may be a risk factor for OCD in later life.

No association between BDNF Val66Met polymorphism and treatment response in obsessive-compulsive disorder in the Japanese population.

AimBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population.MethodsWe first performed a case–control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD.ResultsWe found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05).ConclusionOur results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population.

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways.

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.