Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

Genome-wide association study identifies new loci associated with OCD.

To date, four genome-wide association studies (GWAS) of obsessive-compulsive disorder (OCD) have been published, reporting a high single-nucleotide polymorphism (SNP)-heritability of 28% but finding only one significant SNP. A substantial increase in sample size will likely lead to further identification of SNPs, genes, and biological pathways mediating the susceptibility to OCD. We conducted a GWAS meta-analysis with a 2-3-fold increase in case sample size (OCD cases: N = 37,015, controls: N = 948,616) compared to the last OCD GWAS, including six previously published cohorts (OCGAS, IOCDF-GC, IOCDF-GC-trio, NORDiC-nor, NORDiC-swe, and iPSYCH) and unpublished self-report data from 23andMe Inc. We explored the genetic architecture of OCD by conducting gene-based tests, tissue and celltype enrichment analyses, and estimating heritability and genetic correlations with 74 phenotypes. To examine a potential heterogeneity in our data, we conducted multivariable GWASs with MTAG. We found support for 15 independent genome-wide significant loci (14 new) and 79 protein-coding genes. Tissue enrichment analyses implicate multiple cortical regions, the amygdala, and hypothalamus, while cell type analyses yielded 12 cell types linked to OCD (all neurons). The SNP-based heritability of OCD was estimated to be 0.08. Using MTAG we found evidence for specific genetic underpinnings characteristic of different cohort-ascertainment and identified additional significant SNPs. OCD was genetically correlated with 40 disorders or traits-positively with all psychiatric disorders and negatively with BMI, age at first birth and multiple autoimmune diseases. The GWAS meta-analysis identified several biologically informative genes as important contributors to the aetiology of OCD. Overall, we have begun laying the groundwork through which the biology of OCD will be understood and described.

Remission and Relapse Across Three Years in Pediatric Obsessive-Compulsive Disorder Following Evidence-Based Treatments.

OBJECTIVE: To examine relapse rates following remission in a 3-year follow-up study in pediatric patients with obsessive-compulsive disorder (OCD) treated with cognitive-behavioral therapy (CBT) in a first step, and either continued CBT or sertraline (randomized selection) in a second step. METHOD: Participants (N = 269) fulfilled DSM-IV OCD criteria with a mean severity on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) of 24.6 (SD = 5.1) and were included in analyses according to intent-to-treat principles. CBT used manualized exposure and response prevention (ERP) during both steps 1 and 2, and step 2 sertraline medication used flexible dosing. The follow-up schedules were timed to 6, 12, 24, and 36 months following step 1 CBT. Remission was defined as a CY-BOCS score ≤10 and relapse as an elevated CY-BOCS score ≥16 in those who had remitted. RESULTS: A good third of our patients were in stable and full remission at all examinations (n = 98, 36.4%). Further, some in remission following treatment (n = 36, 13.4%) had mild OCD at some examinations. Relapses during follow-up were not uncommon (n = 28, 10.4%), but in many patients these improved again (n = 10, 3.7%) and were in remission at the final 3-year follow-up. Furthermore, a considerable proportion (n = 50, 18.6%) of the patients were initial non-remitters to the treatment but achieved remission at some point during the follow-up. In addition, 11.5% (n = 31) had persistent OCD but reached remission by the last follow-up. Finally, a smaller segment of our sample (9.7%, n = 26), did not attain remission at any point during the study. CONCLUSION: Our outcome paints a more promising picture of pediatric OCD long-term outcome than previous studies have done. However, both relapse rates and the presence of initial non-remitters and persistent OCD show that treatments need improvement, particularly for those who respond slowly, partially, or not at all. The lack of a general psychiatric interview at follow-up is a marked limitation. CLINICAL TRIAL REGISTRATION INFORMATION: Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; https://www.isrctn.com; ISRCTN66385119.

Long-term functional impairment in pediatric OCD after and during treatment: An analysis of distinct trajectories.

The present study aimed to: (a) identify latent class trajectories of OCD-related functional impairment, before, during and over three years after stepped-care treatment in children and adolescents with OCD; (b) describe these classes according to pretreatment characteristics; (c) identify predictors of trajectory class membership and (d) examine the relationship of functional impairment trajectory classes with OCD symptom severity trajectory classes. The sample consisted of 266 children and adolescents (aged 7-17 years) with OCD, participating in the Nordic long-term OCD treatment study. Latent class growth analysis was conducted using Child Obsessive-Compulsive Impact Scale-Revised (COIS-R) data from children and parents on seven assessment points over a three-year period. A 3-class solution was identified. The largest class (70.7%) initiated treatment with lower functional impairment and obtained moderate reduction which was maintained over time. The second class (24.4%) initiated with higher functional impairment which rapidly diminished over time. The third and smallest class (4.9%), initiated with moderate functional impairment which remained stable over time. The classes differed on measures of OCD severity and comorbid symptoms. Most participants improved with treatment and maintained low levels of impairment. However, a subgroup distinguished by higher levels of ADHD symptoms, remained at pretreatment levels of impairment throughout.

Body Dysmorphic Symptoms in Youth with Obsessive-compulsive Disorder: Prevalence, Clinical Correlates, and Cognitive Behavioral Therapy Outcome.

The aims of the study were to estimate the prevalence of body dysmorphic symptoms in a sample of children and adolescents with obsessive-compulsive disorder, possible clinical correlates and whether BDD symptoms predict poorer treatment outcomes after cognitive behavioral therapy. The study included 269 children and adolescents with OCD, aged 7-17 years, from Denmark, Sweden, and Norway, who were treated with 14 weekly sessions of manualized, exposure-based CBT. Twenty-one patients (7.8%) had BDD symptoms. BDD symptoms were associated with older age (p = 0.003) and a higher prevalence of comorbid anxiety disorders (p = 0.025). In addition, patients with BDD symptoms endorsed a greater number of OCD symptoms than did those without BDD symptoms. Having symptoms of BDD did not affect the CBT outcome on OCD. The results of the study suggest that CBT for OCD is equally effective for those with and without comorbid BDD symptoms.

Specific Contamination Symptoms are Associated with Experiencing a Limited Response of Cognitive-Behavioral Therapy in Pediatric Patients with OCD.

A recent study identified three distinct treatment-response trajectories in pediatric OCD where higher levels of contamination symptoms predicted a limited response to cognitive-behavioral therapy (CBT). This study extends these findings by examining which specific symptoms characterize limited CBT response from baseline to 3-year follow-up, with an emphasis on contamination symptoms. The study sample comprised 269 pediatric patients with OCD, all receiving stepped-care treatment with manualized CBT. Differences in single item-reporting between the three trajectory groups were examined using linear mixed-effect modeling. Limited responders displayed a higher symptom load across all OCD symptom categories at 3-year follow-up, dominated by contamination symptoms. Five of these (obsessions about dirt and germs, about bodily fluids, about the feeling of contamination and compulsions regarding handwashing and showering) showed persistence from baseline to 3-year follow-up. The results indicate that presence of specific contamination symptoms may influence long-term symptom severity trajectories in young patients with OCD.

[Trichotillomania].

Trichotillomania (TTM) is associated with great psychosocial impairment and reduced quality of life and the lifetime prevalence is 1-3 %. The purpose of this review is to give an up-to-date overview of TTM. It describes the genesis and epidemiology of trichotillomania (TTM), including prevalence in terms of age and gender. The knowledge on the aetiology, phenomenology, and comorbidity of TTM is reviewed. The state of treatment options and implications, the effect of these and the clinical and research related perspectives are presented.

Age differences in children with obsessive-compulsive disorder: symptoms, comorbidity, severity and impairment.

BACKGROUND: Studies on child and adolescent obsessive-compulsive disorder (OCD) indicate that symptom severity is similar across age, but significant age differences of symptom profile and comorbid disorders have been observed. These earlier studies have yielded mixed results, are methodologically heterogenous and tend to have fairly small sample sizes. The current study examines these differences in one of the largest samples to date and the first sample outside of an English-speaking cultural context. METHODS: We compared children aged 11 years and younger to adolescents aged 12 years and older from the Nordic Long-Term Obsessive-Compulsive Disorder Treatment Study that included 269 children and adolescents with a primary diagnosis of OCD. The two groups were compared on measures of OCD severity, symptom profile, comorbid symptoms, and functional impairment. RESULTS: Results showed that the younger group had a poorer level of insight, higher rates of ADHD, and disruptive disorders. The older group had higher levels of mental compulsions, miscellaneous obsessions and compulsions, and self-rated functional impairment. No differences were found on the prevalence of anxiety, tic or depressive disorders between the age groups, nor on overall OCD severity. CONCLUSION: Overall, differences between the age groups were found to be less than in previous research. Defining groups by age of onset and duration of illness rather than age at evaluation did not change results. Mental health services in Scandinavia are free of cost, making early intervention more accessible, which may reduce subsequent secondary problems and explain these findings.

The role of early-life family composition and parental socio-economic status as risk factors for obsessive-compulsive disorder in a Danish national cohort.

Research on early-life family environment on obsessive-compulsive disorder (OCD) risk is limited, and sex differences have not been sufficiently studied. We investigated early-life family composition and parental socio-economic status (SES) as OCD risk factors while stratifying for sex in a sample of 1,154,067 individuals from the Danish population (7550 of whom had OCD). Data on early-life family composition (birth order, number of siblings, number of parents in household at proband age 6), parental SES at age 6 (parental income, occupation, and education level), history of parental psychiatric illness, and parental age at birth on OCD risk (i.e., an ICD-10 diagnosis of F42.x) were obtained from Danish population registers. Survival analyses using Cox regression were performed with age as the underlying time variable. Analyses were adjusted for calendar time, and differential effect by sex was tested for exposures. We found that birth order and advanced maternal age were risk factors for OCD in males, and being an only child was associated with increased OCD risk in both sexes. Early childhood SES variables including parental education, occupation, and income were associated with OCD risk, and these effects were more pronounced in females. Significant interaction effects for parental education/occupation and the presence of non-OCD psychiatric diagnoses in the proband also emerged. Our results suggest that early-life SES and family composition may be important risk factors for OCD, and heterogeneity in OCD cases in terms of psychiatric comorbidities, as well as sex differences should be carefully examined in relation to risk factors.

Quality of life in pediatric patients with obsessive-compulsive disorder during and 3 years after stepped-care treatment.

The present study aimed to investigate the long-term quality of life (QoL) in a large sample of pediatric obsessive-compulsive disorder (OCD) patients. The study included 220 pediatric OCD patients from the Nordic Long-term OCD Treatment Study (NordLOTS) who were evaluated at seven time points before, during, and after stepped-care treatment over a 3-year follow-up period. Data from three symptom severity trajectory classes formed the basis of the QoL evaluation: acute (n = 127, N = 147), slow (n = 46, N = 63), and limited responders (n = 47, N = 59). Patients' QoL was assessed using parent and child ratings of the revised Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R). QoL was analyzed by trajectory class using a random mixed effects model. The association between pre-treatment factors and long-term QoL was investigated across classes in a multivariate model. Three years after treatment, the acute responder class had reached QoL levels from a general population, whereas the limited responder class had not. The slow responder class reached norm levels for the child-rated QoL only. Higher levels of co-occurring externalizing symptoms before treatment were associated with lower parent-rated QoL during follow-up, while adolescence and higher levels of co-occurring internalizing symptoms were associated with lower child-rated QoL during follow-up. For some patients, residual OCD symptoms in the years after treatment, even at levels below assumed clinical significance, are associated with compromised QoL. Co-occurring symptoms could be part of the explanation. Assessing QoL after OCD treatment, beyond the clinician-rated symptom severity, could detect patients in need of further treatment and/or assessment. Trial registry: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com ; ISRCTN66385119.

Treatment Gains Are Sustainable in Pediatric Obsessive-Compulsive Disorder: Three-Year Follow-Up From the NordLOTS.

OBJECTIVE: This study evaluated the long-term outcomes of a stepped care treatment for pediatric obsessive-compulsive disorder (OCD) and investigated whether response to first-step cognitive-behavioral therapy (CBT) is an important indicator of 3-year outcomes. METHOD: This study is a part of the Nordic Long-term OCD Treatment Study (NordLOTS), in which 269 children and adolescents were treated with CBT. Nonresponders to CBT were randomized to extended treatment with continued CBT or pharmacotherapy with sertraline. Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores no higher than 15 and no higher than 10 were defined as treatment response and remission, respectively. Participants were assessed 2 and 3 years after first-step CBT. Linear mixed-effects models were used to analyze the outcomes. RESULTS: Intent-to-treat analyses showed a significant decrease in CY-BOCS total score from baseline (24.6) to 3-year follow-up (5.0; p = .001), with a mean decrease of 5.9 from after treatment to 3-year follow-up. Three years after treatment, 90% (n = 242) of participants were rated as responders and 73% were in clinical remission. The duration of treatment did not influence the symptom level at 3-year follow-up (p = .998) and no significant difference was found (p = .169) between the extended treatment conditions. CONCLUSION: The results suggest that evidence-based treatment for pediatric OCD has long-term positive effects, whether a first step of manual-based CBT or extended treatment with CBT or sertraline. The improvements were maintained, and the symptoms decreased further during follow-up and were, after 3 years, similarly independent of treatment duration and form of extended treatment. CLINICAL TRIAL REGISTRATION INFORMATION: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.

Distinct trajectories of long-term symptom severity in pediatric obsessive-compulsive disorder during and after stepped-care treatment.

BACKGROUND: First-line treatments for pediatric obsessive-compulsive disorder (OCD) include exposure-based cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). No studies have thus far identified distinct classes and associated predictors of long-term symptom severity during and after treatment. Yet, these could form the basis for more personalized treatment in pediatric OCD. METHOD: The study included 269 OCD patients aged 7-17 years from the Nordic Long-term OCD Treatment Study (NordLOTS). All participants received stepped-care treatment starting with 14 weekly sessions of manualized CBT. Nonresponders were randomized to either prolonged CBT or SSRIs. Symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale at seven time points from pre- to post-treatment and over a three-year follow-up. Latent class growth analysis (LCGA) was performed to identify latent classes of symptom severity trajectories. Univariate and multivariate analyses were used to detect differences between classes and identify predictors of trajectory class membership including several clinical and demographic variables. TRIAL REGISTRY: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119. RESULTS: Three LCGA classes were identified: (a) acute, sustained responders (54.6%); (b) slow, continued responders (23.4%); and (c) limited long-term responders (21.9%). Class membership was predicted by distinct baseline characteristics pertaining to age, symptom severity, contamination/cleaning and anxiety symptoms. CONCLUSIONS: The LCGA suggests three distinct trajectory classes of long-term symptom severity during and after treatment in pediatric OCD with different clinical profiles at pretreatment. The results point to required clinical attention for adolescent patients with contamination/cleaning and anxiety symptoms who do not show convincing responses to first-line treatment even though they may have reached the established cutoff for treatment response.

Is it time to rethink standard dosage of exposure-based cognitive behavioral therapy for pediatric obsessive-compulsive disorder?

OBJECTIVE: Identifying factors associated with early treatment response is important, because it can help allocate limited resources in psychiatric care more appropriately. This study examined baseline characteristics of participants with early response to exposure-based cognitive behavior therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). METHOD: 269 participants with OCD, aged 7-17 years, were enrolled in a 14-weeks CBT program. We identified participants with early response to treatment, (CY-BOCS total score of ≤15), by the seventh session. RESULTS: At week 7, 248 (92.2%) participants were assessed, 38.3% (95% CI 32.4-44.5%, n = 95) were identified as treatment responders. Univariate analyses showed that six baseline characteristics were significantly associated with early treatment response: young age, lower levels of symptom severity, functional impairment, internalizing- and externalizing problems, depressive symptoms, and family accommodation. CONCLUSIONS: These results suggested that treatment plans for younger children with moderate OCD symptoms and no major comorbid disorder should include briefer and less resource demanding treatment formats than the commonly recommended and applied standard doses of 15 CBT sessions.

Convergent and divergent validity of the schedule for affective disorders and schizophrenia for school-age children - present and lifetime version diagnoses in a sample of children and adolescents with obsessive-compulsive disorder.

The presence of comorbid conditions associated with paediatric obsessive-compulsive disorder (OCD) is reported to range from 50 to 80% and to have an impact on treatment outcome. Accurate identification of comorbid psychiatric disorders is necessary in order to provide personalised care. Reliable and valid diagnostic interviews are essential in the process of establishing the correct diagnoses. The objective of this study was to evaluate the convergent and divergent validity of four diagnose categories generated by the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). The diagnose categories were: anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The K-SADS-PL was applied in a clinical sample of youth aged 7-17 years (N = 269), who were participants in the Nordic long-term OCD-treatment study (NordLOTS). Youth and parents completed measures to evaluate symptoms of anxiety, depression, ADHD, and ODD. Convergent and divergent validity of K-SADS-PL anxiety diagnosis was supported based on both anxiety self- and parent-reports. Similarly, support was found for convergent and divergent validity of ADHD and ODD diagnoses. For depressive disorder, support for convergent validity was found based on the depression self-report. Support for divergent validity of depression was found based on both the depression self- and parent-reports. Results of the present study suggest that the K-SADS-PL generates valid diagnoses of comorbid anxiety disorders, depression disorders, ODD, and ADHD in children and adolescents with OCD.

Hoarding in children and adolescents with obsessive-compulsive disorder: prevalence, clinical correlates, and cognitive behavioral therapy outcome.

Hoarding, common in pediatric obsessive-compulsive disorder (OCD), has specific clinical correlates and is associated with poor prognosis. However, there are few studies of hoarding in pediatric OCD. This study estimates the occurrence of hoarding symptoms in a sample of children and adolescents with OCD, investigating possible differences in demographic and clinical variables between pediatric OCD with and without hoarding symptoms. Furthermore, the study investigates whether hoarding symptoms predict poorer treatment outcomes after cognitive behavioral therapy (CBT). The study sample comprised 269 children and adolescents with OCD, aged 7-17 years, from Denmark, Sweden, and Norway, who were all included in the Nordic long-term obsessive-compulsive disorder Treatment Study. All had an OCD diagnosis according to the DSM-IV and were treated with 14 weekly sessions of manualized, exposure-based CBT. Hoarding symptoms and OCD severity were assessed with the Children's Yale-Brown Obsessive-Compulsive Scale and group differences in treatment outcome were analyzed using linear mixed-effect modelling. Seventy-two patients (26.8%) had one or more symptoms of hoarding. Comorbid tic disorders (p = 0.005) and indecision (p = 0.024) were more prevalent among those with hoarding symptoms than those without hoarding symptoms. In addition, youth with hoarding symptoms had a different OCD symptom profile. Having symptoms of hoarding did not affect CBT outcome (p = 0.933). Results from the study suggest that CBT is equally effective for those with and without hoarding-related OCD.

Obsessive-compulsive symptom dimensions: Association with comorbidity profiles and cognitive-behavioral therapy outcome in pediatric obsessive-compulsive disorder.

Our aims were to examine: (1) classes of comorbid disorders in a sample of children and adolescents with Obsessive-Compulsive Disorder (OCD), (2) how these classes relate to obsessive-compulsive symptom dimensions, and (3) the extent to which obsessive-compulsive symptom dimensions predict Cognitive-Behavioral Therapy (CBT) outcome. Participants (N = 269) were assessed with the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Latent Class Analysis (LCA) was used to identify comorbidity classes. Regression analyses were used to evaluate symptom dimensions as predictors of treatment outcome and their relation to comorbidity classes. Comorbidity was included in the treatment outcome analyses as it can affect outcome. Comorbidity was best categorized by a three-class model and each class was distinctively correlated with the OCD symptom dimensions. Higher scores on the symmetry/hoarding factor increased the chance of responding to CBT by an odds ratio of 1.56 (p = 0.020) when controlled for age, gender, and comorbidity class. The harm/sexual factor (p = 0.675) and contamination/cleaning factor (p = 0.122) did not predict CBT outcome. Three clinically relevant comorbidity subgroups in pediatric OCD were identified. Patients who exhibited higher levels of symmetry/hoarding dimension were more prone to respond to CBT.

The importance of insight, avoidance behavior, not-just-right perception and personality traits in pediatric obsessive-compulsive disorder (OCD): a naturalistic clinical study.

PURPOSE: The primary aim of the present explorative naturalistic study was to examine the association of poor insight, avoidance behavior, and not-just-right sensation with baseline parameters including obsessive-compulsive disorder (OCD) symptoms, baseline severity scores, comorbidity, and personality traits. A second aim was to examine how insight, avoidance and not-just-right sensation influence treatment outcome. MATERIALS AND METHODS: In total, 317 medical records from children and adolescents with OCD referred to a specialized OCD clinic in Denmark were recorded for baseline parameters and treatment outcome. All information was used. RESULTS: Avoidance behavior and poor insight were associated with an increased baseline severity, whereas not-just-right perception was not. Avoidance behavior was associated with the contamination/cleaning subtype, and a not-just-right sensation with the hoarding/symmetry subtype. Lower insight and avoidance behavior were associated with comorbid conditions. At post-treatment, not-just-right perception was associated with a risk of relapse, whereas lower insight was negatively associated with gaining remission. Avoidance behavior reduced the probability of remission and increased the number of offered sessions as well as and the likelihood of having SRI prescribed. Different personality traits were associated with treatment outcome. CONCLUSION: Insight, avoidance behavior, and not-just-right perceptions seem important for baseline severity and post-treatment outcome. Baseline examination should include a systematic description, which could guide treatment. The present study is an explorative study describing a naturalistic clinical population. Therefore, a number of limitations should be taken into consideration when interpreting the results. More systematic studies on the importance of insight, avoidance behavior and not-just-right perceptions are warranted.

Pediatric obsessive-compulsive disorder with tic symptoms: clinical presentation and treatment outcome.

Some studies have shown that children and adolescents with obsessive-compulsive disorder (OCD) and co-morbid tics differ from those without co-morbid tics in terms of several demographic and clinical characteristics. However, not all studies have confirmed these differences. This study examined children and adolescents with OCD and with possible or definite tic specifiers according to the DSM-5 in order to see whether they differ from patients without any tic symptoms regarding clinical presentation and outcome of cognitive behavioral therapy (CBT). The full sample included 269 patients (aged 7-17) with primary DSM-IV OCD who had participated in the Nordic Long-term Treatment Study (NordLOTS). Symptoms of tics were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). One or more tic symptoms were found in 29.9% of participants. Those with OCD and co-morbid tic symptoms were more likely male, more likely to have onset of OCD at an earlier age, and differed in terms of OCD symptom presentation. More specifically, such participants also showed more symptoms of OCD-related impairment, externalization, autism spectrum disorder (ASD), social anxiety, and attention-deficit/hyperactivity disorder (ADHD). However, the two groups showed no difference in terms of OCD severity or outcome of CBT. Children and adolescents with OCD and co-morbid tic symptoms differ from those without tic symptoms in several aspects of clinical presentation, but not in their response to CBT. Our results underscore the effectiveness of CBT for tic-related OCD. CLINICAL TRIALS REGISTRATION: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com ; ISRCTN66385119.

DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent Patients with OCD.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents. The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex-matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome. Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of diagnosis. Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and baseline severity. To our knowledge, this is the first study to examine the DNA methylation profiles in OCD. The study points towards possible differences in the methylation profiles and suggests a correlation with the severity of OCD. However, the results warrant further studies in larger sample sets.

Tics Moderate Sertraline, but Not Cognitive-Behavior Therapy Response in Pediatric Obsessive-Compulsive Disorder Patients Who Do Not Respond to Cognitive-Behavior Therapy.

OBJECTIVE: The purpose of this study was to investigate whether the presence of tic disorder is negatively associated with sertraline (SRT) outcomes, but not with continued cognitive-behavioral therapy (CBT), in a sample of youth who were unresponsive to an initial full course of CBT. METHODS: In the Nordic Long-Term OCD Study, children and adolescents with OCD who were rated as nonresponders to 14 weeks of open-label CBT were randomized to continued CBT (n=28) or SRT treatment (n=22) for an additional 16 weeks of treatment. We investigated whether the presence or absence of comorbid tic disorder moderated treatment outcomes on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). RESULTS: Twelve out of 50 (24.0%) participants were diagnosed with comorbid tic disorder, with 7 receiving continued CBT and 5 receiving SRT, respectively. In patients without tic disorder, results showed no significant between-group differences on average CY-BOCS scores. However, in patients with comorbid tic disorder, those who received SRT had significantly lower average CY-BOCS scores than those who received continued CBT. CONCLUSIONS: Children and adolescents with OCD and comorbid tic disorder, who are nonresponders to an initial 14 week course of CBT, may benefit more from a serotonin reuptake inhibitor (SRI) than from continued CBT.