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Background: Despite the significant personal and societal burden of tic disorders (TD), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor and identifying risk genes could accelerate progress in the field., Methods: Expanding upon previous sample size limitations, we added 4,800 new TD cases and 971,560 controls, conducting a GWAS meta-analysis with 9,619 cases and 981,048 controls of European ancestry. We attempted to replicate the results in an independent deCODE Genetics GWAS (885 TD cases and 310,367 controls). To characterize GWAS findings, we conducted several post-GWAS gene-based and enrichment analyses., Results: A genome-wide significant hit (rs79244681, p=2.27x10 -08 ) within MCHR2-AS1 was identified, though it was not replicated. Post-GWAS analyses revealed a 13.8% SNP-heritability and three significant genes: BCL11B, NDFIP2, and RBM26. Common variant risk for TD was enriched within genes preferentially expressed in the cortico-striato-thalamo-cortical circuit (including the putamen, caudate, nucleus accumbens, and Brodman area 9) and five brain cell types (excitatory and inhibitory telencephalon-, inhibitory- di- and mesencephalon, hindbrain-, and medium spiny neurons). TD polygenic risk was enriched within loss-of-function intolerant genes (p=0.0017) and high-confidence neurodevelopmental disorder genes (p=0.0108). Of 112 genetic correlations, 43 were statistically significant, showing high positive correlations with most psychiatric disorders. Of the two SNPs previously associated with TD, one (rs2453763) replicated in an independent sub-sample of our GWAS (p=0.00018)., Conclusions: This GWAS was still underpowered to identify high-confidence, replicable loci, but the results suggest imminent discovery of common genetic variants for TD., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Children and adolescents with obsessive-compulsive disorder (OCD) are at risk for long-term adversity, but factors influencing long-term outcomes are unclear. A general factor of psychopathology, often referred to as the p factor, captures variance shared by all mental disorders and has predicted long-term outcomes in youth with anxiety and depressive disorders. The p factor has never been examined in relation to outcomes in pediatric OCD. Here, we examine whether the p factor predicts 4 important outcomes over both short and long durations in youth with OCD., Method: We used data from the Nordic Long-term OCD Treatment Study (NordLOTS), in which youth with OCD (N = 248, mean age = 12.83 years [SD = 2.72], 51.6% girls) received exposure-based cognitive-behavioral therapy. The p factor was estimated using parent-reported Child Behavior Checklist data at baseline and was examined in relation to clinician-rated OCD severity, clinician-rated psychosocial functioning, self-reported depressive symptoms, and self- and parent-reported quality of life directly after treatment and 1, 2, and 3 years after treatment., Results: The p factor was associated with acute treatment outcomes for OCD severity and psychosocial functioning, but not for depressive symptoms and quality of life. For the long-term outcomes, the p factor was significantly associated with all outcomes except OCD severity. The p factor outperformed traditional psychiatric comorbidity as a predictor of long-term outcomes., Conclusion: Youth with OCD who experience symptoms across multiple psychiatric domains have poorer long-term outcomes. Compared to traditional classification of psychiatric diagnoses, assessing psychopathology using a dimensional p factor approach may be advantageous for informing prognosis in pediatric OCD., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Family accommodation (FA) involves the actions taken by family members, particularly parents, to accommodate a child´s obsessive-compulsive disorder (OCD) symptoms, reducing distress or impairment. This behavior may maintain compulsive and avoidant behavior, preventing corrective learning or habituation. This study aims to investigate the prevalence and factors influencing FA in a large Scandinavian sample of children with OCD. We assessed 238 children using standardized diagnostic interviews, OCD symptom severity assessments and questionnaires evaluating functional impairment and internalizing and externalizing symptoms. FA was measured using the Family Accommodation Scale, a 12-item clinician-rated interview. Our results confirmed a high frequency of accommodation, with approximately 70% of primary caregivers reporting some accommodation daily and 98% at least once per week. FA was associated with increased OCD symptom severity, contamination/cleaning symptoms, internalizing and externalizing behavior, and functional impairment. Linear regression analysis showed that high levels of FA are specifically associated with lower age, higher OCD symptom severity, parent-reported impairment, internalizing, and externalizing symptoms. A path analysis revealed that FA partially mediated the relationship between OCD severity, externalizing symptoms, and child's age, highlighting the role of FA in the progression of OCD and related symptoms. The findings emphasize the importance of evaluating FA before initiating treatment and specifically addressing it during the therapeutic process., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Declaration of Competing Interest Dr. Thomsen has served on the Advisory Board for the Tryg Foundation and has received speaking honoraria from Medice and Shire within the last three years. Dr. Storch has received research support from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, the International OCD Foundation, the Ream Foundation, Greater Houston Community Foundation, and the Texas Higher Education Coordinating Board. He has received royalties from Elsevier Publications, Springer Publications, American Psychological Association, Wiley, Inc, and Lawrence Erlbaum. He has served on the Speaker's Bureau and Scientific Advisory Board for the International OCD Foundation. He is a consultant for Biohaven and Brainsway. He has received research support from the McIngvale Presidential Endowed Chair. Dr. Lidewij Wolters receives royalties from Springer Media for co-authorship of a Dutch treatment protocol for pediatric OCD. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

It is unknown if long-term remission for pediatric obsessive-compulsive disorder (OCD) patients is associated with post-treatment OCD symptom severity. The aim of the present study was to evaluate if post-treatment symptom severity cut-offs can discriminate remitters from non-remitters in pediatric OCD patients during three years of follow-up. All participants (N = 269) from the Nordic Long-term OCD Treatment Study (NordLOTS) undergoing stepped-care treatment were included. Patients were rated with the Clinical Global Impression - Severity Scale (CGI-S) one (n = 186), two (n = 167), and three years (n = 166) after first-line cognitive-behavioral therapy. Post-treatment symptom severity scores as well as percentage reductions during treatment evaluated with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were analyzed using receiver operating characteristics according to the CGI-S remission scores (< 2) at follow-up. Post-treatment CY-BOCS severity scores acceptably discriminated remitters from non-remitters at one-year follow-up, but poorly for the two- and three-year follow-up. Severity percentage reduction during treatment did not discriminate remission status acceptably at any follow-up point. Post-treatment OCD symptom severity status seems to have little discriminative value for long-term remission status in pediatric patients. Further research is warranted to detect post-treatment factors of prognostic value., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: Limited studies are available that investigate the reactions to COVID-19 pandemic by people suffering from obsessive-compulsive disorder (OCD). Due to the nature of the pandemic and the heightened focus on contamination, cleaning, and social distancing, it is likely that a deterioration of OCD symptoms and severity will be seen., Aims: Our aims were to evaluate (1) self-reported changes in OCD symptom severity of adults with OCD during the COVID-19 pandemic outbreak, (2) whether the COVID-19 pandemic would trigger self-reported contamination symptoms in persons with no history of such symptoms, (3) self-reported variables associated with OCD symptom severity change, and 4) self-reported changes in quality of life., Method: A 47-item self-report questionnaire was sent to all members of the Danish OCD Association and the final sample comprised 201 adult participants. The association of OCD severity change with demographic and clinical variables was analyzed using linear regression., Results: 61.2% of participants reported an increase in OCD severity, based on the retrospective self-report. Female gender, self-reported contamination symptoms, and self-reported psychiatric comorbidity were found to have a significant association with increasing OCD severity. Five participants reported the emergence of contamination symptoms and two of harm related symptoms. Thirty participants reported a severe reduction in quality of life (≥80)., Conclusions: A large group of people suffering from OCD may require special attention and care during a pandemic like COVID-19 in order to lessen the deterioration of OCD symptoms and also to minimize the reduction in quality of life evident in this group.

Background: Chronic tic disorders are neurodevelopmental disorders that can be treated with Habit Reversal Training (HRT) and Exposure Response Prevention (ERP). Intermediate and long-term effects have been examined after individual treatment with HRT, whereas evaluation of long-term outcome after an initial treatment with ERP, or a combination of HRT and ERP is lacking. The present study examines the long-term effect after a combined treatment with HRT and ERP delivered in an individual or a group setting METHODS: Fifty-nine children and adolescents diagnosed with a chronic tic disorder were randomised to manualised treatment combining HRT and ERP as individual or group training. Forty-seven were re-examined 1 year after acute outcome. Outcome measures included Total Tic Severity score (TTS) measured by the Yale Global Tic Severity Scale (YGTSS) and Beliefs About Tics Scale (BATS) RESULTS: In a mixed model, it was shown that the initial improvement with both individual and group treatment was maintained throughout the follow-up period. There were no significant differences between the two methods of treatment delivery. Of all participants completing the 12 months evaluation, 74.4% were considered responders. There was a significant positive association between the reduction of TTS and the reduction in BATS. In a latent class post-treatment trajectory analysis, two classes were identified, where high baseline severity increased the likelihood of being in the lesser responder class. Similar, but only as a trend, having ADHD, planning difficulties or hypersensitivity increased the risk of a lesser response., Conclusions: The present study compares the efficacy in individualised and group treatment of providing manualised therapy for child and adolescent tic disorders using two behavioural methods (combined HRT and ERP) both of which have been shown to have acute benefits but only one of which has been validated for longer term effectiveness. In the present study, both individualised and group treatments showed benefit throughout a 1-year follow-up period with several potential confounds affecting outcomes, while the relative benefits of either HRT and ERP were not addressed. Trial registration NCT04594044, 1-10-72-216-15, registered 19th October 2020, retrospectively registered, https://register.clinicaltrials.gov/prs/app/template/Home.vm?uid=U0005BW2&ts=9&sid=S000ABEY&cx=-wlx7vb The study is approved by the National Ethical Committee (1-10-72-216-15) and the Danish Data Protection Agency (1-16-02-490-15), registered 12 October 2015.

Background: Obsessive compulsive disorder (OCD) is a distressing psychiatric disorder. Traumas may trigger or aggravate OCD symptoms. COVID-19 pandemic has coursed a global crisis and has been associated with onset of psychiatric disorders in adults. Little is known about children/adolescents with OCD. The present study aimed to examine how children/adolescents with OCD react towards COVID-19 crisis., Methods: A questionnaire was distributed to two separate groups of children/adolescents. One group was a clinical group newly diagnosed at a specialized OCD clinic. All the children/adolescents had a current close contact to a therapist or doctor. The other group was a survey group identified through the Danish OCD Association. Most of these children/adolescents were diagnosed years ago, and their primary treatment was completed. For the clinical group, data from patient files was available., Results: In both groups, but most pronounced in the survey group, participants experienced a worsening of their OCD, anxiety, and depressive symptoms. The aggravation of OCD correlated with the worsening of anxiety, depressive symptoms, and the extent of avoidance behavior. For both groups, OCD aggressive symptoms predicted a significant worsening. Poor baseline insight showed a trend to predict a symptom worsening. The worsening was most pronounced in children with early age of onset and a family history of attention deficit hyperactivity disorder., Conclusions: To our knowledge, this is one of the first studies examining the effect of COVID-19 in children/adolescents with OCD. The effect was examined in two separate populations strengthening the findings. The study points towards an influence of the OCD phenotype, baseline insight suggesting a continued vulnerability, and a family history of psychiatric disorders., Trial Registration: The study is approved by the Danish Data Protection Agency (1-16-02-147-20) registered 1st of April 2020. Oral and written information was given to parents and patients and written consent from patients over 15 years and parents were received.

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., (© 2019 Association for Child and Adolescent Mental Health.)

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., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Chronic tic disorders may have a major impact on a child's function. A significant effect has been shown for combined habit reversal training (HRT) and exposure response prevention (ERP) treatment delivered in an individual and group setting., Aims: The present study examines predictors and moderators of treatment outcome after an acute therapeutic intervention., Method: Fifty-nine children and adolescents were randomised to manualised treatment combining HRT and ERP as individual or group training. Age, gender, baseline tic severity, Premonitory Urge for Tics Scale (PUTS) scores, Beliefs about Tic Scale (BATS) scores, hypersensitivity and comorbid psychiatric symptoms were analysed as predictors of outcome. The same characteristics were examined as moderators for individual versus group treatment. Outcome measures included the change in total tic severity (TTS) score and functional impairment score (as measured by the Yale Global Tic Severity Scale (YGTSS))., Results: Internalising symptoms predicted a lesser decrease in functional impairment. The occurrence of obsessive-compulsive symptoms predicted a larger decrease in TTS. Baseline hypersensitivity and high scores on depressive symptoms favoured individual treatment. High baseline PUTS scores favoured group therapy., Conclusions: This is the first study examining factors predicting and moderating perceived functional impairment following a therapeutic intervention. The study adds to the knowledge on predictors and moderators of TTS. Furthermore, this is the first study examining the effect of the BATS score. The study points towards factors that may influence treatment outcome and that require consideration when choosing supplemental treatment. This applies to comorbid anxiety and depressive symptoms, and to the child's belief about their tics and premonitory urge., Declaration of Interest: None.

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.

The knowledge of obsessive-compulsive disorder (OCD) and its treatment has advanced in the latest years and is summarised in this review. Child and adolescent OCD is a chronic condition, and if it is left untreated, it often continues into adulthood with debilitating effect on the quality of life. Cognitive-behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents, and continued CBT or selective serotonin reuptake inhibitor treatment can be effectively given to non-responders to initial CBT. There is also emerging evidence supporting the long-term effect of CBT in this group of patients, and new variations of CBT are being investigated.

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.

Chronic tic disorders may have a huge influence on quality of life. Habit reversal training (HRT) and exposure response prevention (ERP) are effective treatments. In a blinded assessed, open trial, this study evaluates the effectiveness of a newly developed Scandinavian tic treating manual designed to treat adolescents with a chronic tic disorder, combining HRT and ERP. The study compared the efficacy of treatment based on the same manual delivered either individually or in groups. The study was an open randomized controlled clinical trial in which adolescents were randomized to either individual or group therapy. Both therapies included nine sessions. The parents were offered group-based psycho-education. The exclusion criteria were chosen to design a study that would be close to clinical practice. This is the first Scandinavian study that examines the effectiveness of a treatment manual combining HRT and ERP delivered in an individual and group setting. The study showed a significant reduction of the Total Tic score on the Yale Global Tic Severity Scale both in the individual (effect size 1.21) and group setting (effect size 1.38). A total of 66.7% of participants were considered responders. There was no statistical significant difference between the individual and group setting apart from the functional impairment score. The reductions were comparable with those shown in other studies. The participants applied both HRT and ERP, and the majority (36/59) reported an increased post-treatment experience of control. The newly designed Scandinavian manual was equally effective in the individual and group setting with effect sizes comparable with those shown in other studies.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

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.

The underlying structure of obsessive-compulsive disorder (OCD) remains to be confirmed in child and adolescent populations. In this paper we report the first factor analytic study of individual OCD items from Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). OCD symptoms were assessed using the CY-BOCS symptom checklist in a sample of 854 patients with OCD (7-18 years of age) recruited from clinics in five countries. Pooled data were subjected to exploratory and confirmatory factor analysis (CFA) to identify the optimal factor structure. Various models were tested for age and gender subgroups. Also, the invariance of the solution across age and gender was tested and associations with demographic and clinical factors were explored. A three-factor model provided the best-fit solution. It consisted of the following factors: (1) harm/sexual, (2) symmetry/hoarding, (3) contamination/cleaning. The factor structure was invariant for age and gender across subgroups. Factor one was significantly correlated with anxiety, and factor two with depression and anxiety. Factor three was negatively correlated with tic disorder and attention-deficit/hyperactivity disorder (ADHD). Females had higher scores on factor two than males. The OCD symptom structure in children and adolescents is consistent across age and gender and similar to results from recent child and adolescents although hoarding may not be a separate factor. Our three-factor structure is almost identical to that seen in early studies on adults. Common mental disorders had specific patterns of associations with the different factors.

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.

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.

Expert guidelines recommend cognitive-behavior therapy (CBT) as a first-line treatment in pediatric obsessive-compulsive disorder (OCD) and the addition of selective serotonin reuptake inhibitors when CBT is not effective. However, the recommendations for CBT non-responders are not supported by empirical data. Our objective was to investigate the effectiveness of sertraline (SRT) versus continued CBT in children and adolescents that did not respond to an initial course of CBT. Randomized controlled trial conducted in five sites in Denmark, Sweden and Norway, 54 children and adolescents, age 7-17 years, with DSM-IV primary OCD were randomized to SRT or continued CBT for 16 weeks. These participants had been classified as non-responders to CBT following 14 weekly sessions. Primary outcomes were the CY-BOCS total score and clinical response (CY-BOCS <16). The study was a part of the Nordic Long-Term OCD Treatment Study (NordLOTS). Intent-to-treat sample included 50 participants, mean age 14.0 (SD = 2.7) and 48 (n = 24) males. Twenty-one of 28 participants (75%) completed continued CBT and 15 of 22 participants (69.2%) completed SRT. Planned pairwise comparison of the CY-BOCS total score did not reveal a significant difference between the treatments (p = .351), the response rate was 50.0% in the CBT group and 45.4% in the SRT group. The multivariate χ (2) test suggested that there were no statistically significant differences between groups (p = .727). Within-group effect sizes were large and significant across both treatments. These large within-group effect sizes suggest that continued treatment for CBT non-responders is beneficial. However, there was no significant between-group differences in SRT or continued CBT at post-treatment.

Importance: Tourette syndrome/chronic tic disorder (TS/CT) and obsessive-compulsive disorder (OCD) overlap in their phenomenological features and often co-occur in affected individuals and families. Understanding how these disorders cluster in families provides important clinical information and is an important step in understanding the causes of these disorders., Objective: To determine familial recurrence for TS/CT and OCD using a national epidemiologic sample., Design, Setting, and Participants: We performed a population-based study of national health registries in Denmark, including all individuals (n = 1 741 271) born in Denmark from January 1, 1980, through December 31, 2007, and followed up through December 31, 2013. We identified those with TS/CT and/or OCD., Main Outcomes and Measures: The prevalence of TS/CT and OCD and relative recurrence risk (RRR) for TS/CT or OCD among individuals with an oldest sibling or a parent diagnosed as having TS/CT or OCD compared with individuals without an affected oldest sibling or an affected parent., Results: In this sample, 5596 individuals were diagnosed as having TS/CT; 6191, OCD; and 412, both disorders. The overall cohort prevalence of TS/CT was 0.42% (95% CI, 0.41%-0.43%) and of OCD, 0.84% (95% CI, 0.81%-0.87%). The mean sibling recurrence risk for TS/CT across all birth years was 9.88% (95% CI, 8.02%-12.16%) and for OCD, 4.01% (95% CI, 2.78%-5.76%). The sibling RRR for TS/CT was 18.63 (95% CI, 15.34-22.63). In contrast, the sibling RRR for OCD was 4.89 (95% CI, 3.45-6.93). The parent-offspring RRR for TS/CT was 61.02 (95% CI, 44.43-83.82), whereas the parent-offspring RRR for OCD was 6.25 (95% CI, 4.82-8.11). The sibling and parent-offspring cross-disorder risks were also significant, ranging from 3.20 (95% CI, 2.22-4.62) to 10.27 (95% CI, 5.17-20.39)., Conclusions and Relevance: Tourette syndrome/CT and OCD cluster in families. The familial aggregation of TS/CT is profound and substantially higher than the familial aggregation for OCD. The recurrence risk estimates provide an important clinical framework for identifying individuals at risk and provide insights into the causes of these disorders.

Objective: To identify predictors of treatment response in a large sample of pediatric participants with obsessive-compulsive disorder (OCD). The Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study (NordLOTS) included 269 children and adolescents, 7 to 17 years of age, with a DSM-IV diagnosis of OCD. Outcomes were evaluated after 14 weekly sessions of exposure-based cognitive-behavioral therapy (CBT)., Method: The association of 20 potential predictors, identified by literature review, along with their outcomes, was evaluated using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) posttreatment. A CY-BOCS total score of ≤15 was the primary outcome measure., Results: The univariate analyses showed that children and adolescents who were older had more severe OCD, greater functional impairment, higher rates of internalizing and externalizing symptoms, and higher levels of anxiety and depression symptoms before treatment had significantly poorer outcomes after 14 weeks of treatment. However, only age was a significant predictor in the multivariate model., Conclusion: In the multivariate analysis, only age predicted better treatment outcome. Using univariate analysis, a variety of predictors of poorer treatment outcome after CBT was identified. The high impact of comorbid symptoms on outcome in pediatric OCD suggests that treatment should address comorbidity issues. The lack of a family predictor may be related to high family involvement in this study. Future research strategies should focus on optimizing intervention in the presence of these characteristics to achieve greater benefits for patients with OCD. Clinical trial registration information-Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119., (Copyright © 2015 American Academy of Child & Adolescent Psychaitry. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to examine the acute effectiveness of manualized exposure-based CBT with a family-based treatment, as an initial treatment for pediatric OCD delivered in regular community child and adolescents outpatient clinics. The report summarizes outcome of the first treatment step in the NordLOTS, which was conducted in Denmark, Sweden and Norway., Method: 269 participants, age 7-17, with OCD, received treatment for 14 weekly sessions. Treatment response was defined as CY-BOCS score of ≤15 at post treatment., Results: 241 participants (89.6%) completed all 14 weeks of treatment. Treatment response among the completers was 72.6% (95% CI 66.7%-77.9%). Mixed effects model revealed a statistically significant effect of time F(1,479) = 130.434. Mean symptom reduction on the CY-BOCS was 52.9% (SD = 30.9). The estimated within-group effect size between baseline and post treatment was 1.58 (95% CI: 1.37-1.80)., Conclusion: This study found that manualized CBT can be applied effectively in community mental health clinics. These findings underscore the feasibility of implementing exposure-based CBT for pediatric OCD in a regular child and adolescent mental health setting., Clinical Trials Registration Information: This study was registered in Current Controlled Trials; Nordic Long-term Obsessive-compulsive disorder (OCD) Treatment Study (www.controlled-trials.com ISRCTN66385119)., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This paper describes and discusses the methodology of the Nordic long-term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was to study treatment outcome of CBT, to identify CBT non- or partial responders and to investigate whether an increased number of CBT-sessions or sertraline treatment gives the best outcome; to identify treatment refractory patients and to investigate the outcome of aripiprazole augmentation; to study the outcome over a three year period for each responder including the risk of relapse, and finally to study predictors, moderators and mediators of treatment response., Methods: Step 1 was an open and uncontrolled clinical trial with CBT, step 2 was a controlled, randomised non-blinded study of CBT non-responders from step 1. Patients were randomized to receive either sertraline plus CBT-support or continued and modified CBT. In step 3 patients who did not respond to either CBT or sertraline were treated with aripiprazole augmentation to sertraline., Conclusions: This multicenter trial covering three Scandinavian countries is going to be the largest CBT-study for paediatric OCD to date. It is not funded by industry and tries in the short and long-term to answer the question whether further CBT or SSRI is better in CBT non-responders.

Background: Obsessive-compulsive disorder (OCD) is a frequent and clinically heterogeneous disorder. The complex clinical presentation can be summarized using a few consistent and temporally stable symptom dimensions. Only few studies in children and adolescents have examined the importance of symptom dimensions., Aims: This retrospective study was undertaken to describe the relation between symptom dimensions, pattern of comorbidity and family disposition, in a sample of Danish children and adolescents with OCD assessed in a naturalistic setting., Methods: A retrospective study of children and adolescents (n=83) diagnosed with OCD in the period 1998-2004, at the Psychiatric Hospital for Children and Adolescents, Risskov, Denmark. Information from clinical records was systematically collected and Children's Yale-Brown Obsessive-compulsive Scale (CY-BOCS) scores and symptom checklists were obtained., Results: High scores on the symmetry/ordering dimension were related to OCD in first-degree relatives and high scores on the aggressive/checking dimension were associated to comorbidity with tic disorders. We showed a correlation between limited insight and younger age., Conclusion: This is one of the first studies to examine symptom dimensions in children and adolescents in naturalistic settings. The results were comparable with those in adult studies, showing an association between the occurrence of the symmetry/ordering dimension and family OCD and the occurrence of the aggressive/checking dimension and comorbid tic disorders. In small children, insight into symptoms may be limited.

Obsessive compulsive disorder (OCD) is a frequent condition. First-choice psychopharmacological treatment includes SSRIs where the choice of drug depends on the occurrence of side effects. If remission is obtained, continued treatment is recommended for at minimum of one year. If only a partial or no response is obtained, augmentation treatment with atypical antipsychotics may be attempted. However, only few studies have examined the effect and side effects of augmentation treatment in children and adolescents. The aim was to provide a summary on the current knowledge on psychopharmacological treatment of children and adolescents with OCD.

Obsessive-compulsive disorder (OCD) is a frequent disorder and glutamate seems to be an important transmitter. The effect of glutamate depends on the level as well as the effect mediated through glutamate receptors. The level is altered in brain areas that are involved in OCD. Genes encoding receptors, enzymes involved in the metabolism and transport proteins are located in regions that are related to OCD. Pharmacogenetic studies examining the genetic variations in the glutaminate system are lacking. The aim was to examine the current knowledge on the glutaminate system in the development and maintenance of OCD.

OCD is a frequently encountered disorder which can have a major impact on the development of children and adolescents. The recommended treatment is cognitive behavioural therapy (CBT) which can be combined with psychopharmacological treatment. Studies have shown that CBT both as an individual treatment, as treatment in groups or as a family-based treatment is effective. The choice of treatment depends on the age of the patient, family relations, including the involvement of the parents, the severity of the symptoms and the occurrence of comorbidity.

Obsessive-compulsive disorder (OCD) is a frequently encountered disorder in children and adolescents. Several characteristics make the disorder a challenge to diagnostic methods and treatment procedures including the diversity of symptoms, the delay of referral and the occurrence of comorbidity. The aim of the present study was to examine how recent progress in assessment and treatment has influenced the Danish clinicians in their work with children and adolescents with OCD. The study was conducted as a national survey addressing a total of 14 outpatient children and adolescent departments, and 25 medical specialists in private practice. The clinicians received a questionnaire including general and specific questions on assessment scales and treatment methods towards OCD and their view on treatment efficacy and prognosis. A total of 71.8% responded to the questionnaire. Most clinicians reported the use of a general medical and social history combined with the use of OCD-specific checklists. Treatment procedures included medication, cognitive therapy or cognitive-behavioural therapy and a family approach depending on the age of the patient. Eighty-one per cent of the clinicians reported a good or very good effect of treatment. Clinical Global Improvement ratings of the last treated patient indicated a treatment response of 68.8% and a response on general improvement of 59.4%. In conclusion, the present study shows that treatment methods employed towards children and adolescents with OCD are close to the clinical recommendations and comparable with those employed in other countries. Furthermore, the general opinion of clinicians towards OCD is comparable with that described in the literature. However, a discussion of the choice of recommended assessment methods including the use of both specific and general checklists is warranted.

To determine whether swift foxes (Vulpes velox) could facilitate transmission of Yersinia pestis to uninfected black-tailed prairie dog (Cynomys ludovicianus) colonies by acquiring infected fleas, ectoparasite and serologic samples were collected from swift foxes living adjacent to prairie dog towns during a 2004 plague epizootic in northwestern Texas, USA. A previous study (1999-2001) indicated that these swift foxes were infested almost exclusively with the flea Pulex irritans. Black-tailed prairie dogs examined from the study area harbored only Pulex simulans and Oropsylla hirsuta. Although P. irritans was most common, P. simulans and O. hirsuta were collected from six swift foxes and a single coyote (Canis latrans) following the plague epizootic. Thus, both of these canids could act as transport hosts (at least temporarily) of prairie dog fleas following the loss of their normal hosts during a plague die-off. All six adult swift foxes tested positive for antibodies to Y. pestis. All 107 fleas from swift foxes tested negative for Y. pestis by mouse inoculation. Although swift foxes could potentially carry Y. pestis to un-infected prairie dog colonies, we believe they play only a minor role in plague epidemiology, considering that they harbored just a few uninfected prairie dog fleas (P. simulans and O. hirsuta).

Background: Studies indicate that major depressive disorder (MDD) is frequent in children but that it may be missed. This study determines the incidence of hospital-treated MDD based on the frequency of MDD in child psychiatric patients, and analyses effects of age and gender on depressive symptoms and psychiatric comorbidity., Methods: One hundred ninety-nine consecutive child psychiatric patients were interviewed using a semi-structured diagnostic interview (K-SADS-PL). Comorbidity and symptoms were compared across age and gender., Results: Current or partly remitted MDD was found in 42 children (21%). Thirty-eight (90%) had comorbid psychiatric disorder(s). Onset of the comorbid disorder was prior to onset of depression in 74% of cases. No significant gender-differences were found, but anhedonia, hypersomnia and decreased ability to concentrate were more frequent in the older age group. In contrast, feelings of worthlessness were more frequent in the younger age group. The number of melancholic symptoms was significantly associated with older age., Conclusion: MDD is frequent in child psychiatric patients aged 8-13 years. Age-but not gender-had significant effects on melancholy score and the prevalence of specific symptoms. Results suggest that MDD may be underdiagnosed in clinical samples unless careful examined with diagnostic interview.

Background: Enkephalins are opioid peptides that can modulate immune responses and inflammatory processes. Furthermore, they inhibit keratinocyte proliferation/differentiation in vitro. Previously, we have shown that enkephalins are present in increased amounts in lesional psoriasis., Objective: To determine the effect of topical treatment with the vitamin D analogue calcipotriol and the corticosteroid mometasone furoate on the level of methionine-enkephalin (enk) in psoriatic lesions., Methods: Twelve psoriatic patients were treated with calcipotriol and mometasone furoate for 14 days without or with hydrocolloid occlusion. Keratome biopsies were obtained from treated and untreated skin, and the extracted enk was quantified by radioimmunoassay. Furthermore, punch biopsies were obtained for immunohistochemical analysis., Results: Clinically, both calcipotriol and mometasone furoate improved psoriasis to the same degree, the effects being more pronounced after occlusion. Histologically, treatment with mometasone furoate without occlusion decreased both the epidermal thickness/parakeratosis and the number of dermal immunocompetent cells (CD3- and CD68-positive cells). In contrast, treatment with calcipotriol without occlusion reduced the epidermal thickness and the degree of parakeratosis but decreased the number of CD3- and CD68-positive cells only slightly. The mean enk level was decreased by 26 and 86% by calcipotriol without and with occlusion and by 16 and 63% by mometasone furoate without and with occlusion, respectively. The decreases in the enk levels corresponded to the degree of clinical improvement but not to the histological changes., Conclusion: The increased levels of enk in psoriatic lesions are reduced in parallel with the clinical improvement induced by a topical vitamin D analogue and a corticosteroid. Because enkephalins can modulate epidermal differentiation and inflammatory processes, the findings indicate that enkephalins may play a role in the pathogenesis of psoriasis.

The opioid peptides enkephalins have been shown to modulate inflammatory responses and keratinocyte proliferation and differentiation. Furthermore, increased levels of enkephalin are present in psoriatic lesions. The purpose of the present study was to determine the effect of natural sunlight combined with salt water bathing in the Dead Sea on the methionine-enkephalin (e.n.k.) level in psoriatic skin. Ten patients were treated at the Dead Sea for 4 weeks, and keratotome biopsies were obtained before and after treatment. The amount of enkephalin extracted from the biopsies was measured by radioimmunoassay. Treatment at the Dead Sea resulted in a complete clinical clearance of psoriasis, and immunohistochemical stainings of lesional skin showed that the treatment decreased both epidermal thickness/parakeratosis and the dermal infiltration of CD3- and CD68-positive cells, although the number of CD3- and CD68-positive cells became normal in only two of the 10 cases. However, there was only a slight decrease in the mean enk levels (21%). Furthermore, the level of enk was high in non-lesional psoriatic skin after treatment at the Dead Sea, and immunostaining showed that, in some patients, the treatment induced a mild epidermal hyperplasia and a dermal infiltration of CD3- and CD68-positive cells. Enkephalin-like immunoreactivity was detected in the cytoplasm of both epidermal keratinocytes and dermal infiltrating cells. To determine whether the relatively high skin enk levels after treatment at the Dead Sea was caused by ultraviolet (UV) radiation, normal volunteers were exposed to a single dose of UVA and UVB (2 minimal erythema doses). UVA, but not UVB, irradiation stimulated the mean enk level in the irradiated skin by about sixfold. Furthermore, multiple whole-body UVA irradiations not only resulted in increased skin levels of enk, but also in increased plasma levels. In conclusion, natural sunlight combined with salt water bathing cleared psoriasis without causing a significant decrease in lesional enk levels. Furthermore, non-lesional enk levels were increased. These findings may be the result of a direct stimulatory effect of UVA irradiation on enk formation in the skin. It is possible that the increased circulating levels of enk after UV exposure may contribute to the beneficial effects of UVA irradiation.

Opioid peptides are a group of neuropeptides which include enkephalins, endorphins and dynorphins. In addition to their central and peripheral antinociceptive function, opioids can modulate immune activity and cell proliferation. Previously, we have shown that enkephalins are present in macrophages infiltrating the dermal papillae in involved psoriatic skin and that the amount of enkephalin is significantly increased in involved psoriatic skin. Because enkephalins were detected close to the epidermis, we examined the effects of opioid peptides on the differentiation (transglutaminase type 1 activity and cytokeratin 10 expression) and proliferation (MTT assay) of cultured human keratinocytes. Enkephalins (methionine-enkephalin, leucine-enkephalin and the synthetic DADL) inhibited cell differentiation dose-dependently, while beta-endorphin had no effect. The opioid receptor antagonist naltrexone completely antagonized the inhibitory effect of methionine-enkephalin and leucine-enkephalin, but not that of DADL. Furthermore, methionine-enkephalin had a slight inhibitory effect on the proliferation of keratinocytes. Enkephalin was detected in unstimulated keratinocyte cultures, and naltrexone alone stimulated keratinocyte differentiation. These results indicate that enkephalins may play a role in the differentiation of epidermal keratinocytes. It remains to be determined whether the enkephalin detected in psoriatic skin are sufficient to affect epidermal differentiation in vivo.