Variants of exposure therapy are effective for treating obsessive-compulsive and related disorders (OCRDs). However, significant numbers of patients do not respond adequately to exposure therapy resulting in continued distress and functional impairment. Therefore, novel approaches to augmenting exposure therapy are needed to adequately treat non- and partial-responders. Emerging research suggests that interventions that augment learning and memory processes associated with exposure therapy (i.e., extinction training) may display promise in enhancing treatment response in OCRDs. As the most studied example, d-cycloserine (DCS) is a relatively safe cognitive enhancer that appears to accelerate treatment gains associated with exposure therapy. This article reviews research on the use of DCS and other putative cognitive modifiers as they relate to the treatment (or prospective treatment) of obsessive-compulsive disorder and other OCRDs.
Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.
Clinical studies in adults and children with obsessive-compulsive disorder (OCD) have shown that d-cycloserine (DCS) can improve treatment response by enhancing fear extinction learning during exposure-based psychotherapy. Some have hypothesized that improved treatment response is a function of increased compliance and engagement in therapeutic homework tasks, a core component of behavioral treatment. The present study examined the relationship between DCS augmented cognitive-behavioral therapy (CBT) and homework compliance in a double-blind, placebo controlled trial with 30 youth with OCD. All children received 10 CBT sessions, the last seven of which included exposure and response prevention paired with DCS or placebo dosed 1 h before the session started. Results suggested that DCS augmented CBT did not predict improved homework compliance over the course of treatment, relative to the placebo augmented CBT group. However, when groups were collapsed, homework compliance was directly associated with treatment outcome. These findings suggest that while DCS may not increase homework compliance over time, more generally, homework compliance is an integral part of pediatric OCD treatment outcome.
Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.
Cigarette smoking is more prevalent among individuals with psychiatric disorders than the general population. Obsessive-compulsive disorder (OCD) may be an intriguing exception, although no recent study has investigated this hypothesis in OCD patients. Moreover, it is unknown whether reduced smoking rates are present in unaffected first-degree relatives of OCD patients.
Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.
Sensory phenomena (SP) are disturbing sensations, feelings or urges. Although such feelings are often found in obsessive-compulsive disorder (OCD) and Tourette's Syndrome (TS) patients, sensory phenomena are usually not addressed in assessment measures. The University of São Paulo's Sensory Phenomena Scale (USP-SPS) was designed to measure sensory phenomena among all ages of patients with OCD and TS, and it was validated in Portuguese.
Pediatric anxiety disorders have high prevalence rates and morbidity and are associated with considerable functional impairment and distress. They may be predictors for the development of other psychiatric disorders and, without intervention, are more likely to persist into adulthood. While evidence-based pharmacological and behavioral interventions are currently available, there remains a sizable subset of youth who remain only partially treatment-responsive and therefore symptomatic following treatment. Novel methods of treatment, pharmacologic and non-pharmacologic, including acceptance and commitment therapy (ACT), attention bias modification (ABM), d-cycloserine (DCS) augmentation of cognitive behavioral treatment (CBT), and glutamatergic agents such as riluzole, are briefly introduced and discussed.
Despite extensive use of the Childrens Yale Brown Obsessive Compulsive Scale (CYBOCS; Scahill et al., 1997), the lack of normative data impedes interpretation of individual CYBOCS scores. Consequently, psychometrics on CYBOCS severity scores from 815 treatment-seeking youth with obsessive-compulsive disorder (OCD) are presented, across age and sex, so that normative comparisons of obsessive, compulsive, and combined obsessive-compulsive severity could be calculated. Our findings suggest no evidence for marked age or sex differences. Further, obsessive-compulsive symptom severity scores (measured via the CYBOCS) appear consistent with global OCD syndrome severity (measured via the Clinician Global Impression-Severity scale [CGI-S; Guy, 1976]; r = .58). This study contributes the 1st empirically based guidelines for interpreting obsessive-compulsive symptom severity scores. After a diagnosis of OCD is determined, the CYBOCS can be used to determine severity of illness (however, categories of severity proposed by this article should not be used in the screening of OCD symptoms). Findings can facilitate clinicians and investigators ability to draw comparisons across obsessive-compulsive severity scores. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
The development of microsatellite loci has become more efficient using next-generation sequencing (NGS) approaches, and many studies imply that the amount of applicable loci is large. However, few studies have sought to quantify the number of loci that are retained for use out of the thousands of sequence reads initially obtained. We analyzed the success rate of microsatellite loci development for three amphibian species using a 454 NGS approach on tetra-nucleotide motif-enriched species-specific libraries. The number of sequence reads obtained differed strongly between species and ranged from 19,562 for Triturus cristatus to 55,626 for Lissotriton helveticus, with 52,075 reads obtained for Calotriton asper. PHOBOS was used to identify sequences with tetra-nucleotide repeat motifs with a minimum repeat number of ten and high quality primer binding sites. Of 107 sequences for T. cristatus, 316 for C. asper and 319 for L. helveticus, we tested the amplification success, polymorphism, and degree of heterozygosity for 41 primer combinations each for C. asper and T. cristatus, and 22 for L. helveticus. We found 11 polymorphic loci for T. cristatus, 20 loci for C. asper, and 15 loci for L. helveticus. Extrapolated, the number of potentially amplifiable loci (PALs) resulted in estimated species-specific success rates of 0.15% (T. cristatus), 0.30% (C. asper), and 0.39% (L. helveticus). Compared with representative Illumina NGS approaches, our applied 454-sequencing approach on specifically enriched sublibraries proved to be quite competitive in terms of success rates and number of finally applicable loci.
Obsessive-compulsive disorder (OCD) is marked by the presence of obsessions and/or compulsions that cause significant interference in an individuals life. Insight regarding symptoms in youth with OCD may affect accurate assessment, acceptance and motivation for treatment, tolerance of negative valence states (i.e., fear) and treatment outcome, so assessment of this construct and associated clinical characteristics is important. Accordingly, the current study sought to expand the literature on symptom insight by examining multi-informant ratings of insight from children, parents, and clinicians simultaneously and its relationship to varied clinical characteristics. One-hundred and ten treatment-seeking youth with a primary diagnosis of OCD, aged 6-17, participated in the study along with a parent/guardian. The nature of symptom conviction, fixity of ideas, and perceptions about the cause of the problems were important indicators in assessing child insight and resulted in a comprehensive, psychometrically-sound measure of insight. Insight was generally not strongly associated with clinical characteristics. Poor insight was moderately associated with less resistance of obsessive-compulsive symptoms, increased externalizing symptoms, and ordering symptoms. Overall, this study contributes further information into the nature and correlates of insight in youth with OCD, and provides a psychometrically sound approach for its assessment.
This study reports on the development and initial psychometric properties of the Childrens Saving Inventory (CSI), a parent-rated measure designed to assess child hoarding behaviors. Subjects included 123 children and adolescents diagnosed with primary Obsessive-Compulsive Disorder (OCD) and their parents. Trained clinicians administered the Childrens Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), items assessing Family Accommodation and the Clinical Global Impressions--Severity index. Parents completed the CSI, Child Obsessive-Compulsive Impact Scale (COIS)--Parent Version and Child Behavior Checklist. Youth completed the COIS--Child Version, Obsessive-Compulsive Inventory Child Version (OCI-CV), Multidimensional Anxiety Scale for Children, and Childrens Depression Inventory--Short Form. A four factor solution was identified; factors were named Discarding, Clutter, Acquisition, and Distress/Impairment. Internal consistency for the CSI Total and factor scores were good. One-week test-retest reliability (n = 31) from a random subsample was excellent. Known groups validity was supported vis-à-vis higher CSI scores for those endorsing hoarding on the CY-BOCS Symptom Checklist. Convergent and discriminant validity was evidenced by weak relationships with OCI-CV Checking and Contamination factors but strong relationships with the OCI-CV Hoarding factor and with hoarding obsession/compulsions on the CY-BOCS. These findings provide initial support for the reliability and validity of the CSI for the assessment of hoarding behaviors among youth with OCD. Future studies are needed to extend these findings to non-OCD samples of youth.
Obsessive-compulsive disorder (OCD) influences not only patients but also family members. Although the construct of family accommodation has received attention in OCD literature, no measures of overall family functioning are currently available. The OCD Family Functioning (OFF) Scale was developed to explore the context, extent, and perspectives of functional impairment in families affected by OCD. It is a three-part, self-report measure capturing independent perspectives of patients and relatives. A total of 400 subjects were enrolled between 2008 and 2010 from specialized OCD clinics and OCD research studies. Psychometric properties of this scale were examined including internal consistency, test-retest reliability, convergent and divergent validity, and exploratory factor analyses. Both patient and relative versions of the OFF Scale demonstrated excellent internal consistency (Cronbachs alpha coefficient = 0.96). The test-retest reliability was also adequate (ICC = 0.80). Factor analyses determined that the OFF Scale comprises a family functioning impairment factor and four OCD symptom factors that were consistent with previously reported OCD symptom dimension studies. The OFF Scale demonstrated excellent convergent validity with the Family Accommodation Scale and the Work and Social Adjustment Scale. Information gathered regarding emotional impact and family role-specific impairment was novel and not captured by other examined scales. The OFF Scale is a reliable and valid instrument for the clinical and research assessment of family functioning in pediatric and adult OCD. This will facilitate the exploration of family functioning impairment as a potential risk factor, as a moderator and as a treatment outcome measure in OCD.
Tourettes disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands.
SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive-compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886–892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family-based association analyses in 1,576 participants in 377 families.We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three-SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD.
A history of separation anxiety disorder (SAD) is frequently reported by patients with obsessive-compulsive disorder (OCD). The purpose of this study was to determine if there are clinical differences between OCD-affected individuals with, versus without, a history of SAD.
Recently, research in pediatric obsessive-compulsive disorder (OCD) has expanded to include large family genetic studies, elaboration of phenotypic dimensions, description of co-morbid disorders and their moderating effects on treatment response and outcome, research on immune-based neuropsychiatric causes, randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs), randomized controlled trials of cognitive behavioral therapy (CBT), comparative treatment trials; new approaches in behavior therapy, and increased awareness of newer approaches to treatment. The purpose of this article is to review assessment and treatment strategies to include current advances in research.
The extant literature supports an association between psychological trauma and development of OCD in adults, and this link is a plausible mediator for environment-gene interactions leading to phenotypic expression of OCD. Objective: To explore the relationship between OCD and traumatic life events in children and adolescents.
Research on the neural circuitry underlying fear extinction has led to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, as a method to enhance exposure therapy outcome. Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood anxiety disorder. Thus, we sought to preliminarily examine whether weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD).
To explore bidirectional comorbidity between bipolar disorder (BPD) and obsessive-compulsive disorder (OCD) in youth and to examine the symptom profile and clinical correlates of both disorders in the context of reciprocal comorbidity and ascertainment status.
This paper describes the use of Differential Scanning Calorimetry (DSC) to evaluate the impact of varying mix ratios of bio-oil (pyrolysis oil) and bio-diesel on the oxidation stability and on some cold flow properties of resulting blends. The bio-oils employed were produced from the semi-continuous Auger pyrolysis of pine pellets and the batch pyrolysis of pine chips. The bio-diesel studied was obtained from poultry fat. The conditions used to prepare the bio-oil/bio-diesel blends as well as some of the fuel properties of these blends are reported. The experimental results suggest that the addition of bio-oil improves the oxidation stability of the resulting blends and modifies the crystallization behavior of unsaturated compounds. Upon the addition of bio-oil an increase in the oxidation onset temperature, as determined by DSC, was observed. The increase in bio-diesel oxidation stability is likely to be due to the presence of hindered phenols abundant in bio-oils. A relatively small reduction in DSC characteristic temperatures which are associated with cold flow properties was also observed but can likely be explained by a dilution effect.
The current study examined factors associated with obsessive-compulsive disorder (OCD) related functional impairment among 99 youth with OCD. A trained evaluator administered the Childrens Yale-Brown Obsessive-Compulsive Scale, items assessing family accommodation, and a version of the Brown Assessment of Beliefs Scale that was modified for children. Youth completed the Child Obsessive-Compulsive Impact Scale-Child Version, Obsessive-Compulsive Inventory-Child Version, Multidimensional Anxiety Scale for Children, and Childrens Depression Inventory-Short Form. The childs parent completed the Child Obsessive-Compulsive Impact Scale-Parent Version. Results indicated that OCD symptom severity, depressive symptoms, and family accommodation were directly related to impairment, while insight was inversely related to functional impairment. Insight, family accommodation, and depressive symptoms predicted parent- and/or child-rated functional impairment above and beyond OCD symptom severity. Among symptom dimensions, contamination/cleaning and aggressive/checking symptoms were the only dimensions significantly associated with impairment. Assessment and treatment implications are discussed; specifically, we highlight how the variables of interest may impact clinical presentation and treatment course.
Although obsessions and compulsions comprise the main features of obsessive-compulsive disorder (OCD), many patients report that their compulsions are preceded by a sense of "incompleteness" or other unpleasant feelings such as premonitory urges or a need perform actions until feeling "just right." These manifestations have been characterized as Sensory Phenomena (SP). The current study presents initial psychometric data for a new scale designed to measure SP.
The main aim of this study was to examine the moderating effects of attention deficit hyperactivity disorder (ADHD) on anxiety disorders in children. Data were analyzed from a large referred sample of children with anxiety disorder without comorbid ADHD (anxiety disorder, N = 253), anxiety disorder plus comorbid ADHD (anxiety disorder + ADHD, N = 704), and ADHD without comorbid anxiety disorder (ADHD, N = 511). Children were comprehensively assessed, including by structured diagnostic interview (K-SADS-E). Overall rates of individual anxiety disorders, as well as age of onset and severity of illness were not significantly different in the presence of comorbid ADHD. School functioning in children with anxiety disorders was negatively impacted by the presence of comorbid ADHD. Frequency of mental health treatment in children with anxiety disorders was significantly increased in the presence of comorbid ADHD. ADHD had a limited impact on the manifestation of anxiety disorder in children suggesting that ADHD and anxiety disorders are independently expressed.
This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD).
Exposure-based cognitive-behavioral therapy and serotonin reuptake inhibitor medications are efficacious treatment options for the management of pediatric obsessive-compulsive disorder. Despite established efficacy, many youths receiving either therapy remain symptomatic after acute treatment. Regardless of the rationale for persistent symptoms, a clear need emerges for treatment options that restore functioning efficiently to symptomatic youths. One innovative approach builds upon the identified role of NMDA receptors in the fear extinction process. Instead of breaking existing connections during fear extinction, new associations develop that eventually predominate over prior associations. Recent investigations have explored augmenting exposure-based cognitive-behavioral therapy with the NMDA partial agonist d-cycloserine, with preliminary results demonstrating expedited treatment gains and moderately larger effects above exposure and response prevention therapy alone. A large randomized clinical trial is underway to evaluate the efficacy and efficiency of this therapeutic combination in pediatric obsessive-compulsive disorder. Results from this trial may translate into improved management practices.
This study examined differences in clinical presentation and functional impairment in youth with obsessive-compulsive disorder (OCD) with or without comorbid depressive disorders and sought to determine the predictors of youth-reported depressive symptoms. One-hundred and sixty youth were reliably diagnosed with OCD and comorbid disorders using the Anxiety Disorders Interview Schedule for DSM-IV: Parent version (Silverman and Albano, 1996) and confirmed by an experienced clinician. Sixteen percent (n = 25) had a comorbid diagnosis of a current depressive disorder (DD). Significantly more females than males had a DD. Those with a DD showed increased OCD symptom severity, OCD-related functional impairment, and family accommodation relative to those without a comorbid DD. Depressive symptoms were significantly positively correlated with years of age, degree of OCD symptom severity, measures of OCD-related functional impairment, and non-OCD anxiety symptoms. Hierarchical regression analyses showed that age, gender, functional impairment, and non-OCD anxiety were significant predictors of depressive symptoms, even when OCD symptom severity was controlled. Notably, functional impairment was a partial mediator of the relationship between OCD symptom severity and depression levels, suggesting depression levels are the product of both degree of symptoms and amount of day-to-day impairment. Results are discussed in terms of implications for assessment and treatment.
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