Publications by authors named "Daniel Geller"

104 Publications

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Mov Disord 2021 May 4. Epub 2021 May 4.

Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.

Objective: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.

Methods: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.

Results: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.

Conclusions: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28593DOI Listing
May 2021

Neurocognitive endophenotypes in pediatric OCD probands, their unaffected parents and siblings.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Feb 18;110:110283. Epub 2021 Feb 18.

Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

Background: Limited extant research on neurocognitive endophenotypes in obsessive-compulsive disorder (OCD) show inconsistent results. Limitations of this body of literature include small sample sizes, strict exclusion criteria, lack of objective standard normalized test scores, and significant lack of studies utilizing pediatric probands. This study aimed to address these limitations.

Methods: A large carefully screened cohort of pediatric OCD (n = 102), their unaffected siblings (n = 78), and parents (n = 164), completed a neuropsychological battery. To compare participants at different ages and developmental stages, standard scores were computed using test norms. Cluster-robust regression with sample size-adjusted sandwich estimates of variance, and interclass correlations were computed. False Discovery Rate procedures were employed to correct for multiplicity.

Results: Probands, siblings and parents demonstrated deficient task performance (Z < -0.5) on the 'number of trials to complete first category' on the Wisconsin Card Sorting Test, and on the Stroop color naming trials. Compared to test norms, the three groups exhibited medium to large effect sizes on these outcome measures. No other meaningful familial trends were found.

Conclusions: OCD probands, their unaffected siblings and parents exhibited deficiencies in specific subdomains of cognitive flexibility and inhibitory control, namely, initial concept formation and proactive control, which may be valid candidate neurocognitive endophenotypes of OCD. No other meaningful familial effect has been found on other functions, including other executive function indices such as perseverations and interference control. These results highlight the need to carefully examine individual outcomes from executive function tests instead of the tendency to focus largely on major outcome measures.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110283DOI Listing
February 2021

Towards a definitive symptom structure of obsessive-compulsive disorder: a factor and network analysis of 87 distinct symptoms in 1366 individuals.

Psychol Med 2021 Feb 9:1-13. Epub 2021 Feb 9.

Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.

Background: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.

Methods: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM).

Results: Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables.

Conclusions: Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.
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http://dx.doi.org/10.1017/S0033291720005437DOI Listing
February 2021

Positive Outcomes of Rapid Freeware Implementation to Replace Baccalaureate Student Clinical Experiences.

J Nurs Educ 2020 Dec;59(12):701-704

Background: Loss of in-person clinical experiences due to the COVID-19 pandemic created the need for a rapid transition to online clinical education using virtual simulation, which has been shown to be an effective teaching-learning method. Standards of best practice for simulation provide a framework for implementation.

Method: Using free online simulation programs, 15 faculty members offered 3-hour synchronous sessions covering 20 different topics via an online meeting platform to 42 senior nursing students. Students were invited to complete an evaluation following each session.

Results: Students collectively logged over 1,200 hours of simulation time attending approximately 100 sessions. Postsimulation evaluations captured students' responses to sessions. Students appreciated the opportunity to review content covered in previous semesters and engaged most when simulations followed a consistent structure, were interactive, and contained visually engaging materials.

Conclusion: Resourceful faculty responded quickly and creatively to the urgent need to transition to online clinical learning and created positive experiences for students. [J Nurs Educ. 2020;59(12):701-704.].
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http://dx.doi.org/10.3928/01484834-20201118-08DOI Listing
December 2020

The moderating effect of age on the associations of cognitive and metacognitive beliefs with pediatric OCD symptoms.

Cogn Behav Ther 2021 Mar 19;50(2):104-120. Epub 2020 Oct 19.

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine , Houston, TX, USA.

Although considerable research has highlighted the importance of cognitive and metacognitive beliefs in adult obsessive-compulsive disorder (OCD), there has been limited investigation of these beliefs in pediatric OCD. The present study investigated the clinical correlates of cognitive and metacognitive beliefs in pediatric OCD. Previous studies found positive relations between OCD symptoms and these beliefs in pediatric patients, and we hypothesized these beliefs would also be positively related to pediatric OCD symptom severity. We additionally hypothesized age would moderate these relationships in consideration of previous studies highlighting age differences in symptom presentation and self-reported beliefs. We also explored age differences in belief endorsements. Youth aged 7-17 (n = 142) diagnosed with OCD completed self-report scales to measure cognitive and meta-cognitive beliefs. OCD severity was assessed using self-report and clinician-rated measures. Pearson correlations, moderation analyses, and independent-samples t-tests were used to test our hypotheses and aims. Significant positive relationships were observed between cognitive and metacognitive beliefs and self-reported OCD severity, although age did not moderate these relationships. Age differences were found in belief endorsements. In conclusion, cognitive and metacognitive beliefs appear clinically relevant to pediatric OCD cases, and we recommend clinicians assess these beliefs and incorporate cognitive components to corresponding evidence-based treatment.
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http://dx.doi.org/10.1080/16506073.2020.1819866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897238PMC
March 2021

User-Driven Functional Movement Training With a Wearable Hand Robot After Stroke.

IEEE Trans Neural Syst Rehabil Eng 2020 10 4;28(10):2265-2275. Epub 2020 Sep 4.

We studied the performance of a robotic orthosis designed to assist the paretic hand after stroke. It is wearable and fully user-controlled, serving two possible roles: as a therapeutic tool that facilitates device-mediated hand exercises to recover neuromuscular function or as an assistive device for use in everyday activities to aid functional use of the hand. We present the clinical outcomes of a pilot study designed as a feasibility test for these hypotheses. 11 chronic stroke (>2 years) patients with moderate muscle tone (Modified Ashworth Scale ≤ 2 in upper extremity) engaged in a month-long training protocol using the orthosis. Individuals were evaluated using standardized outcome measures, both with and without orthosis assistance. Fugl-Meyer post intervention scores without robotic assistance showed improvement focused specifically at the distal joints of the upper limb, suggesting the use of the orthosis as a rehabilitative device for the hand. Action Research Arm Test scores post intervention with robotic assistance showed that the device may serve an assistive role in grasping tasks. These results highlight the potential for wearable and user-driven robotic hand orthoses to extend the use and training of the affected upper limb after stroke.
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http://dx.doi.org/10.1109/TNSRE.2020.3021691DOI Listing
October 2020

Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders.

Behav Res Ther 2020 Jul 28;133:103697. Epub 2020 Jul 28.

Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 400, Houston, TX, 77030, USA.

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.
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http://dx.doi.org/10.1016/j.brat.2020.103697DOI Listing
July 2020

Recent evidence of nurse practitioner outcomes in a variety of care settings.

J Am Assoc Nurse Pract 2020 Jul 7. Epub 2020 Jul 7.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia.

When nurse practitioners (NPs) work to expand their scope of practice through state legislatures, the opposing lobbying groups are often physician-led organizations. The main argument against NP independence and limited scope of practice is that NP care is inherently inferior to that of physicians. However, more than three decades of research demonstrates quality and cost outcomes to be equal to or better than that of physicians. This article reviews a wide range of evidence documenting NP competency, satisfaction, and safety, as well as the challenges and consequences when limiting NP scope of practice. The evidence is clear and has not changed in over 30 years, NPs provide access to and effective primary care in a variety of settings, equal in quality outcomes and safety, and cost-effective compared with physicians.
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http://dx.doi.org/10.1097/JXX.0000000000000451DOI Listing
July 2020

When Science Challenges Our Long-Held Assumptions About the Robustness of Evidence for Standard of Care.

J Am Acad Child Adolesc Psychiatry 2020 07 25;59(7):792-793. Epub 2020 Jun 25.

Massachusetts General Hospital, Harvard Medical School, Boston.

In this issue of the Journal, we publish two letters pertaining to the article "Systematic Review and Meta-analysis: Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in Children and Adolescents" by Uhre et al. Their protocol employed the Cochrane Handbook for Systematic Reviews of Interventions to evaluate risk of bias (selection, performance, detection, attrition, and reporting biases) in the included 25 trials, contacting trial authors to obtain missing data where possible. They controlled for random errors owing to sparse data or multiple testing using Trial Sequential Analysis and evaluated the certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation approach. They concluded that cognitive-behavioral therapy (CBT) (versus no intervention) is effective for pediatric obsessive-compulsive disorder (OCD), but that the certainty of evidence was low or very low for all outcomes and that moderator analyses could often not be completed for lack of data. The authors made the point that blinding is always possible, even in CBT trials.
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http://dx.doi.org/10.1016/j.jaac.2020.05.003DOI Listing
July 2020

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders.

Int Clin Psychopharmacol 2020 07;35(4):173-193

Department of Psychiatry, Bellvitge University Hospital-IDIBELL, University of Barcelona, Cibersam, Barcelona, Spain.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.
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http://dx.doi.org/10.1097/YIC.0000000000000314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255490PMC
July 2020

Death and Dying in the Emergency Department.

Adv Emerg Nurs J 2020 Apr/Jun;42(2):81-89

Emory University Nell Hodgson School of Nursing, Atlanta Georgia (Mr Geller and Dr Evans); and Emory University Hospital, Atlanta Georgia (Dr Evans).

The Research to Practice column is intended to improve the research critique skills of the advanced practice registered nurse (APRN) and to assist with the translation of research into practice. For each column, a topic and a particular research study are selected. The stage is set with a case presentation. The research article is then reviewed and critiqued, and the findings are discussed in relation to the case presented. Our current column discusses factors associated with the quality of the death and dying experience in the emergency department (ED) from the perspective of health care providers with implications for APRN practice and strategies using the following study: . "Exploring the quality of the dying and death experience in the emergency department: An integrative literature review," International Journal of Nursing Studies, 85, 106-117. Our case involves a man with metastatic colon cancer where his oncology nurse practitioner recommends no further treatment and tells him he has approximately 6 months to live.
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http://dx.doi.org/10.1097/TME.0000000000000299DOI Listing
January 2021

OCD and Anxiety: The Annual Review Issue.

J Am Acad Child Adolesc Psychiatry 2020 01;59(1):13-14

Starting in 2018, the Journal began highlighting high-quality reviews in January. We called this our Annual Review Edition. This year, we have again selected a number of reviews to be placed in January, most especially from our recent call for review papers on child and adolescent anxiety and obsessive-compulsive disorder (OCD), which went out in August of 2018. We received multiple excellent submissions, and three are presented in this edition of the Journal.
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http://dx.doi.org/10.1016/j.jaac.2019.11.010DOI Listing
January 2020

Early detection and intervention for obsessive-compulsive disorder in childhood and adolescence.

Lancet Child Adolesc Health 2020 02 26;4(2):99-101. Epub 2019 Nov 26.

Massachusetts General Hospital and Harvard University Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1016/S2352-4642(19)30376-1DOI Listing
February 2020

Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.

J Anxiety Disord 2019 12 23;68:102149. Epub 2019 Sep 23.

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, USA.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).
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http://dx.doi.org/10.1016/j.janxdis.2019.102149DOI Listing
December 2019

New insights and perspectives on the genetics of obsessive-compulsive disorder.

Psychiatr Genet 2019 10;29(5):142-151

Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Switzerland.

Psychiatric genetic research has exploded in search of polygenic risk factors over the past decade, but because of the complexity and heterogeneity of mental illnesses, using the current understanding of the genome has not reached the conclusion of finding a cause for psychiatric disorders. Obsessive-compulsive disorder is a relatively common and often debilitating neuropsychiatric disorder that has not been the primary focus in psychiatric research. Clinicians and researchers who have dedicated to investigate the genetics of obsessive-compulsive disorder have detected a strong genetic involvement. This review will provide an update and a new perspective on the current understanding of the genetics of obsessive-compulsive disorder, which includes epidemiological data, family and twins studies, candidate gene studies, genome-wide association studies, copy-number variants, imaging genetics, epigenetics, and gene-environment interaction.
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http://dx.doi.org/10.1097/YPG.0000000000000230DOI Listing
October 2019

The Centrality of Doubting and Checking in the Network Structure of Obsessive-Compulsive Symptom Dimensions in Youth.

J Am Acad Child Adolesc Psychiatry 2020 07 14;59(7):880-889. Epub 2019 Aug 14.

Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.

Objective: Obsessive-compulsive disorder (OCD) is a heterogeneous condition with well-established symptom dimensions across the lifespan. The objective of the present study was to use network analysis to investigate the internal structure of these dimensions in unselected schoolchildren and in children with OCD.

Method: We estimated the network structure of OCD symptom dimensions in 6,991 schoolchildren and 704 children diagnosed with OCD from 18 sites across 6 countries. All participants completed the Obsessive-Compulsive Inventory-Child Version.

Results: In both the school-based and clinic-based samples, the OCD dimensions formed an interconnected network with doubting/checking emerging as a highly central node, that is, having strong connections to other symptom dimensions in the network. The centrality of the doubting/checking dimension was consistent across countries, sexes, age groups, clinical status, and tic disorder comorbidity. Network differences were observed for age and sex in the school-based but not the clinic-based samples.

Conclusion: The centrality of doubting/checking in the network structure of childhood OCD adds to classic and recent conceptualizations of the disorder in which the important role of doubt in disorder severity and maintenance is highlighted. The present results suggest that doubting/checking is a potentially important target for further research into the etiology and treatment of childhood OCD.
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http://dx.doi.org/10.1016/j.jaac.2019.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219532PMC
July 2020

Avoidance, Insight, Impairment Recognition Concordance, and Cognitive-Behavioral Therapy Outcomes in Pediatric Obsessive-Compulsive Disorder.

J Am Acad Child Adolesc Psychiatry 2020 05 20;59(5):650-659.e2. Epub 2019 Jun 20.

University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada.

Objective: Insight and avoidance are commonly discussed factors in obsessive-compulsive disorder (OCD) that have demonstrated associations with increased severity as well as reduced treatment response in adults, but these factors have not been sufficiently examined in pediatric OCD. This study examined the impacts of avoidance, insight, and impairment recognition concordance on cognitive-behavioral therapy (CBT) outcomes as well as impacts of CBT on insight and avoidance in a large sample of youths affected by OCD.

Method: Data from 573 OCD-affected youths enrolled in CBT trials were aggregated. Children's Yale-Brown Obsessive-Compulsive Scale items measured treatment response, insight, and avoidance. Standardized differences between child and parent ratings of impairment were used to calculate impairment recognition concordance. Binary logistic regression was used to identify variables associated with treatment response.

Results: Greater avoidance, limited child recognition of impairment, older age, and lower baseline severity predicted reduced likelihood of treatment response, but insight did not. Both insight and avoidance improved significantly following CBT. Response rates were lower when posttreatment insight and avoidance were worse.

Conclusion: Contrasting with prevailing belief, poor insight does not appear to limit CBT response potential in pediatric OCD. Avoidance and impairment recognition are understudied CBT response predictors and warrant further consideration in pediatric OCD. Clinicians should attend to these factors to optimize outcomes for children affected by this common, debilitating illness.
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http://dx.doi.org/10.1016/j.jaac.2019.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179819PMC
May 2020

Immune-Related Comorbidities in Childhood-Onset Obsessive Compulsive Disorder: Lifetime Prevalence in the Obsessive Compulsive Disorder Collaborative Genetics Association Study.

J Child Adolesc Psychopharmacol 2019 10 6;29(8):615-624. Epub 2019 Jun 6.

Department of Psychiatry, Faculty of Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.

To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1-5.2]% vs. 1.0%-2.0%,  = 1.491,  < 0.001,  = 1389), encephalitis or meningitis (1.4 [0.9-2.1]% vs. 0.1%-0.4%,  = 5.913,  < 0.001,  = 1393), rheumatoid arthritis (1.1 [0.6-2.0]% vs. 0.2%-0.4%,  = 3.416,  < 0.001,  = 949) and rheumatic fever (0.6 [0.3-1.2]% vs. 0.1%-0.2%,  = 3.338,  < 0.001,  = 1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5 ± 0.9 vs. 2.3 ± 1.0,  = 3.183,  = 0.002,  = 822). These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.
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http://dx.doi.org/10.1089/cap.2018.0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786333PMC
October 2019

Immunoglobulin A Dysgammaglobulinemia Is Associated with Pediatric-Onset Obsessive-Compulsive Disorder.

J Child Adolesc Psychopharmacol 2019 05 20;29(4):268-275. Epub 2019 Mar 20.

4 Allergy, Immunology, and Infectious Disease Program, University of South Florida, St. Petersburg, Florida.

Inflammation and immune dysregulation have been implicated in the pathogenesis of pediatric-onset obsessive-compulsive disorder (OCD) and tic disorders such as Tourette syndrome (TS). Though few replicated studies have identified markers of immune dysfunction in this population, preliminary studies suggest that serum immunoglobulin A (IgA) concentrations may be abnormal in these children with these disorders. This observational retrospective cohort study, conducted using electronic health records (EHRs), identified 206 children with pediatric-onset OCD and 1024 adults diagnosed with OCD who also had testing for serum levels of IgA. IgA deficiency and serum IgA levels in pediatric OCD were compared with IgA levels from children diagnosed with autism spectrum disorders (ASD;  = 524), tic disorders ( = 157), attention-deficit/hyperactivity disorder (ADHD;  = 534), anxiety disorders ( = 1206), and celiac disease, a condition associated with IgA deficiency ( = 624). Compared with ASD and anxiety disorder cohorts, the pediatric OCD cohort displayed a significantly higher likelihood of IgA deficiency (OR = 1.93; 95% CI = 1.18-3.16, and OR = 1.98; 95% CI = 1.28-3.06, respectively), though no difference was observed between pediatric OCD and TS cohorts. Furthermore, the pediatric OCD cohort displayed similar rates of IgA deficiency and serum IgA levels when compared with the celiac disease cohort. The pediatric OCD cohort also displayed the highest percentage of IgA deficiency (15%,) when compared with TS (14%), celiac disease (14%), ADHD (13%), ASD (8%), and anxiety disorder (8%) cohorts. When segregated by sex, boys with OCD displayed a significantly higher likelihood of IgA deficiency when compared with all comparison cohorts except for celiac disease and tic disorders; no significant difference in IgA deficiency was observed between female cohorts. Pediatric OCD subjects also displayed significantly lower adjusted serum IgA levels than the ASD and anxiety disorder cohorts. Adults with OCD were also significantly less likely than children with OCD to display IgA deficiency (OR = 2.71; 95% CI = 1.71-4.28). When compared with children with celiac disease, no significant difference in IgA levels or rates of IgA deficiency were observed in the pediatric OCD cohort. We provide further evidence of IgA abnormalities in pediatric-onset OCD. These results require further investigation to determine if these abnormalities impact the clinical course of OCD in children.
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http://dx.doi.org/10.1089/cap.2018.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227412PMC
May 2019

Sudden gains in cognitive behavioral therapy among children and adolescents with obsessive compulsive disorder.

J Behav Ther Exp Psychiatry 2019 09 9;64:92-98. Epub 2019 Mar 9.

Massachusetts General Hospital and Harvard Medical School, USA.

Background And Objectives: This study examined the occurrence of sudden gains (or reversal of gains) among children with obsessive-compulsive disorder (OCD) during the course of cognitive-behavioral therapy (CBT), as well as the association of sudden gains with treatment response, treatment group, and pre-treatment clinical characteristics.

Methods: The sample consisted of 136 youth (ages 7-17) with a primary diagnosis of OCD who were randomized in a double-blinded fashion to 10 sessions of CBT with augmentation of either d-cycloserine or placebo. Sudden gain status was determined based on clinician-rated obsessive-compulsive symptom severity, which was collected on 9 occasions across the study period.

Results: 42.6% of youth experienced at least one sudden gain, which tended to occur either after starting exposure and response prevention or towards the end of treatment. After applying the Benjamini-Hochberg procedure for multiple comparisons, there were no significant pre-treatment predictors of sudden gains and only reduced insight predicted the reversal of gains. Individuals with at least one sudden gain had improved overall treatment outcomes, measured both by reduction in OCD symptom severity, and by global illness severity.

Limitations: Several clinical constructs were not examined. Symptomatology was not assessed at every treatment session. Differences in those who achieved sudden gains and those who did not may be obscured. There is the possibility that a sudden gain reflected a scoring error generated by an optimistic or inaccurate report. Finally, a relatively homogenous sample may limit the generalizability of results.

Conclusions: The course of CBT for pediatric OCD is variable with many children experiencing sudden gains, but a sizable percentage experience a reversal of gains which was related to reduced insight. Sudden gains tended to occur after starting exposure and response prevention and towards the end of treatment.

Trialsregistration: ClinicaltrialsgovRegistry:NCT00864123. https://www.clinicaltrials.gov/ct2/show/NCT00864123.
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http://dx.doi.org/10.1016/j.jbtep.2019.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520195PMC
September 2019

Fear extinction learning as a predictor of response to cognitive behavioral therapy for pediatric obsessive compulsive disorder.

J Anxiety Disord 2019 05 1;64:1-8. Epub 2019 Mar 1.

Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd, Suite 400, Houston 77030, TX, United States. Electronic address:

Background: While cognitive behavior therapy (CBT) is an effective treatment for many children and adolescents with Obsessive Compulsive Disorder (OCD), therapeutic response is variable. Fear conditioning and extinction are central constructs underlying exposure-based CBT. Fear extinction learning assessed prior to CBT may be a useful predictor of CBT response for guiding treatment decisions.

Methods: Sixty-four youth who participated in a randomized placebo-controlled trial of CBT with and without d-cycloserine (DCS) completed a fear conditioning task. Skin conductance response (SCR) scores were used to measure fear acquisition and extinction to determine whether extinction learning could predict CBT response.

Results: CBT responders and non-responders appeared to acquire conditioned fear SCRs in a similar manner. However, differences between treatment responders and non-responders emerged during the extinction phase. A responder (responder, non-responder) by conditioned stimulus type (CS+, CS-) interaction showed that CBT responders differentiated the stimulus paired with (CS+) and without (CS-) the unconditioned stimulus correctly during early and late extinction, whereas the CBT non-responders did not (p = .004).

Conclusions: While the small sample size makes conclusions tentative, this study supports an emerging literature that differential fear extinction may be an important factor underlying clinical correlates of pediatric OCD, including CBT response.
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http://dx.doi.org/10.1016/j.janxdis.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422704PMC
May 2019

Defining Treatment Outcomes in Pediatric Obsessive-Compulsive Disorder Using a Self-Report Scale.

Behav Ther 2019 03 22;50(2):314-324. Epub 2018 Jun 22.

Baylor College of Medicine.

This study examined benchmarks of treatment response and clinical remission on the Obsessive Compulsive Inventory-Child Version (OCI-CV) for youth with obsessive-compulsive disorder (OCD). Participants were 91 youth who enrolled in a randomized controlled trial that examined the benefit of augmenting cognitive behavior therapy (CBT) with either d-cycloserine or placebo. Youth completed the OCI-CV at baseline, Week 4 (prior to initiating exposure therapy), and posttreatment. Receiver operator curve (ROC) analyses examined optimal benchmarks for treatment response and clinical remission as identified by independent evaluators at the posttreatment assessment using the Clinical Global Impression (CGI) scales of Improvement (CGI-Improvement), Severity (CGI-Severity), and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Optimal benchmarks for treatment response were a 20%-25% reduction in the OCI-CV total score. Meanwhile, optimal benchmarks for remission were a 55%-65% reduction in the OCI-CV total score and a posttreatment total score ≤6-8. OCI-CV benchmarks exhibited moderate agreement with the CY-BOCS for treatment response and clinical remission. Meanwhile, fair agreement was observed for response and remission with CGI scales. A lower pretreatment OCI-CV total score was associated with less agreement between classification approaches. Findings provide benchmarks for classifying treatment response and clinical remission in an efficient manner. Given the moderate agreement between the CY-BOCS and OCI-CV benchmarks, the OCI-CV may serve as a useful alternative when clinician-rated scales cannot be administered due to limited resources (e.g., time, training). Thus, evidence-based measurement can be incorporated to monitor therapeutic response and remission in clinical practice.
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http://dx.doi.org/10.1016/j.beth.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541025PMC
March 2019

Comorbid Psychopathology and the Clinical Profile of Family Accommodation in Pediatric OCD.

Child Psychiatry Hum Dev 2019 10;50(5):717-726

Baylor College of Medicine, Houston, TX, USA.

Family accommodation (FA) has been linked with myriad negative outcomes in pediatric obsessive-compulsive disorder (OCD), but extant literature has yielded differential relationships between FA and clinical variables of interest. Consequently, this study examined the phenomenology, clinical profile, and effects of comorbid psychopathology on FA to better understand these behaviors. A total of 150 youths and their caregivers completed clinician- and self-reported measures at a baseline visit for a larger randomized controlled trial. Sociodemographic variables were not associated with FA, but specific types of OCD symptom clusters were. Higher OC-symptom severity and functional impairment were associated with increased FA. Comorbid anxiety disorders moderated the relationship between OC-symptom severity and FA, but comorbid attention deficit hyperactivity, oppositional defiant, and mood disorders did not. Internalizing and externalizing problems both mediated the relationship between FA and functional impairment. These findings provide clinical implications for important treatment targets and factors that may impact FA.
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http://dx.doi.org/10.1007/s10578-019-00876-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703960PMC
October 2019

Early intervention for obsessive compulsive disorder: An expert consensus statement.

Eur Neuropsychopharmacol 2019 04 14;29(4):549-565. Epub 2019 Feb 14.

Sackler Medical School, Tel Aviv University, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel.

Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the 'toxic' effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed.
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http://dx.doi.org/10.1016/j.euroneuro.2019.02.002DOI Listing
April 2019

D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD: Predictors and moderators of outcome.

J Affect Disord 2018 12 20;241:454-460. Epub 2018 Jul 20.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Suite 2000, Boston, MA 02114, United States.

Background: Over half of children receiving cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD) do not fully remit. To improve response rates and enhance extinction learning, d-cycloserine (DCS) has been examined as an augmenting agent of CBT. To direct children with OCD towards treatments with the highest likelihood of success, the current study evaluated the conditions under which DCS augmentation works best (i.e., moderators) and the baseline characteristics associated with outcome, irrespective of treatment type (i.e., predictors).

Methods: Data came from a two-site randomized controlled trial (N = 142) in which children received either DCS + CBT (n = 70) or placebo + CBT.

Results: No baseline variables moderated the effects of DCS augmentation on CBT outcome. However, several predictor variables were associated with a decreased likelihood of achieving remission status, including higher family accommodation scores, higher impairment scores, higher depression scores, and higher externalizing scores. Furthermore, better insight at pre-treatment was associated with more improvement longitudinally on a clinician-rated summary measure of illness severity.

Limitations: The current study did not examine all variables that had previously been shown to moderate or predict treatment outcome (e.g., family history of OCD or cognitive profile).

Conclusions: The absence of significant moderators suggests that baseline factors cannot yet be used to determine who benefits most from DCS. To maximize treatment benefits for children presenting with identified predictors of worse treatment outcome, clinicians might need to adapt existing CBT protocols and administer additional interventions that address patients' specific problem areas.
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http://dx.doi.org/10.1016/j.jad.2018.07.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129428PMC
December 2018

Symptom Insight in Pediatric Obsessive-Compulsive Disorder: Outcomes of an International Aggregated Cross-Sectional Sample.

J Am Acad Child Adolesc Psychiatry 2018 08;57(8):615-619.e5

University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada.

Insight in obsessive-compulsive disorder (OCD) refers to patients' recognition that their obsessions and compulsions are symptoms rather than necessary or natural thoughts and behaviors. It has been estimated that 20% to 45% of youth with OCD exhibit poor or absent insight. Identified correlates of poor insight include younger age, increased OCD severity, impairment, and family accommodation; lower intellectual and adaptive functioning; and greater depressive symptoms. Poorer insight has also been associated with reduced response across treatment groups (ie, selective serotonin reuptake inhibitor [SSRI], cognitive behavioral therapy [CBT], combined SSRI plus CBT, or pill placebo)..
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http://dx.doi.org/10.1016/j.jaac.2018.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176075PMC
August 2018

Atypical symptom presentations in children and adolescents with obsessive compulsive disorder.

Compr Psychiatry 2018 10 17;86:25-30. Epub 2018 Jul 17.

Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Suite 2000, Boston, MA 02114, United States of America; Harvard Medical School, United States of America; Royal Australasian College of Physicians, Paediatrics, Australia. Electronic address:

Background: Common symptom presentations in youth with Obsessive Compulsive Disorder (OCD) are easily recognized and are included in the Children's Yale Brown Obsessive Compulsive Scale (CY-BOCS) symptom checklist. However, some youth may occasionally present with atypical or unusual symptoms that are less readily recognized as OCD and may be confused with other disorders that sometimes overlap, such as autism spectrum disorder or even psychosis.

Methods: Case synopses which are thematically linked and exemplify and illustrate two distinct types of unusual or atypical symptom presentations are described. These symptoms are embedded in the subjects' broader clinical picture, that more correctly identifies the atypical symptoms as a variant feature of OCD rather than some other diagnostic condition.

Results: We describe twenty-four children with OCD. Twelve children had obsessions related to adverse experiences of places, times or other people that were felt as horrific, abhorrent or disgusting. These obsessions led to contamination fears of any thoughts or actions associated with those places, events or people. In those whose OCD was a reaction to another person, the contamination obsession often took the form of fear of acquiring an unwanted trait or characteristic by association, which was then avoided. Twelve other youth had obsessions driven by a primary sensory experience that was intolerable, including tactile, olfactory, and auditory stimuli. These sensory experiences were sometimes linked to specific objects or people, driving time-consuming repetitive behaviors to avoid or alleviate the sensory discomfort.

Conclusion: Recognition of atypical presentations of OCD, such as fear of contamination by association with adverse experiences and primary sensory intolerance leading to OCD will help clinicians to better identify and treat these unique symptoms.
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http://dx.doi.org/10.1016/j.comppsych.2018.07.006DOI Listing
October 2018

Enduring Effects of Cognitive-Behavioral Therapy for Pediatric Obsessive-Compulsive Disorder: The Nordic Experience.

Authors:
Daniel A Geller

J Am Acad Child Adolesc Psychiatry 2017 11;56(11):918-919

Pediatric Obsessive-Compulsive Disorder and Tic Disorder Program, Massachusetts General Hospital, Boston and Harvard Medical School, Boston. Electronic address:

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http://dx.doi.org/10.1016/j.jaac.2017.09.417DOI Listing
November 2017

Coupled Bimanual Training Using a Non-Powered Device for Individuals with Severe Hemiparesis: A Pilot Study.

Int J Phys Med Rehabil 2017 Jun 28;5(3). Epub 2017 Apr 28.

Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY, USA.

Background: Few options exist for training arm movements in participants with severe post-stroke hemiparesis who have little active range of motion. The purpose of this study was to test the safety and feasibility of training with a non-powered device, the Bimanual Arm Trainer (BAT), to facilitate motor recovery in individuals with severe hemiparesis. The BAT enabled coupled bimanual training of shoulder external rotation, which is reduced in individuals with severe post-stroke hemiplegia. The rationale for bimanual training was to harness contralesional cortical activity to drive voluntary movement in the affected arm in patients who could barely perform unimanual movements.

Methods: Nine participants with post-stroke hemiparesis, preserved passive range of motion and Modified Ashworth score of <3 in the shoulder and elbow joints, trained with the device for 45 minutes, twice a week for six weeks, and were assessed pre- and post-training.

Results: All participants tolerated the training and no adverse events were reported. Participants showed significant improvement in the upper extremity Fugl-Meyer score post-training with an effect size of 0.89. Changes in the flexor synergy pattern accounted for 64.7% of the improvement. Improvement in active range of motion in the paretic limb occurred for both trained and untrained movements. Some participants showed improvement in the time taken to perform selected tasks on the Wolf Motor Function Test post-training.

Conclusion: The results demonstrate the safety and feasibility of using the Bimanual Arm Trainer to facilitate motor recovery in individuals with severe hemiparesis.
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http://dx.doi.org/10.4172/2329-9096.1000404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636010PMC
June 2017

Quality of Life in Children and Youth with Obsessive-Compulsive Disorder.

J Child Adolesc Psychopharmacol 2018 03 14;28(2):104-110. Epub 2017 Sep 14.

8 Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital , Boston, Massachusetts.

Objective: The study examined clinical correlates of quality of life (QoL), impact of treatment on QoL, and predictors of QoL change among children with obsessive-compulsive disorder (OCD).

Methods: One hundred forty-two children with primary OCD who were enrolled as part of a larger clinical trial participated. Children were administered a structured diagnostic interview, as well as clinician-administered measures of OCD and depression symptom severity. Children and parents completed reports of QoL, as well as measures of impairment and internalizing and externalizing symptoms. Youth received 10 sessions of family-based cognitive-behavioral therapy (CBT).

Results: At baseline, QoL was inversely related to obsessive-compulsive symptom severity, impairment, externalizing and internalizing symptoms, and severity of depression symptoms according to children and parents. After CBT, QoL improved according to parent ratings, but not child ratings. None of the predictors examined were associated with changes in QoL scores over time. Impairment, and externalizing and internalizing symptoms predicted QoL after accounting for OCD symptom severity. After accounting for OCD symptoms, externalizing symptoms inversely predicted changes in QoL.

Conclusion: These data suggest that QoL is related to more severe clinical presentation and improves with evidence-based treatment, but QoL improvements may be inversely related to externalizing symptomology.
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http://dx.doi.org/10.1089/cap.2017.0091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831750PMC
March 2018