Treatment of a Child With Obsessive‐Compulsive Disorder With Limited Motivation: Course and Outcome of Cognitive‐Behavior Therapy

Motivation is a key ingredient in the successful treatment of pediatric obsessive‐compulsive disorder (OCD). As a first‐line treatment, cognitive‐behavior therapy (CBT) requires extensive client engagement, including participating in exposures and doing homework tasks. A lack of motivation to comply with these tasks may seriously affect treatment outcome. This case study identifies factors interfering with motivation and illustrates motivational strategies to enhance compliance of a child with OCD. The patient was an 11‐year‐old boy with severe OCD and symptoms of oppositional defiant disorder (ODD). He had extensive OCD‐related avoidance behavior but denied the presence of symptoms or did not acknowledge them as a problem. In this article, we discuss the different techniques used to enhance motivation, which subsequently led to a favorable outcome.     

Primary diagnosis of Whipple's disease in bone marrow

Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable. Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level. This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.     

Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder

The distribution of obsessive compulsive symptoms was compared in 16 individuals with primary obsessive compulsive disorder (OCD) and 16 individuals with Gilles de la Tourette syndrome (GTS) and associated obsessive compulsive behaviors (OCB). The two groups showed significant differences in the distribution of OC symptomatology. Furthermore, those OCD probands who shared a similar symptom profile with GTS individuals all had a positive family history of OCD. All of the other OCD probands were isolated cases. Implications of this finding on the etiology and pathogenesis of the two disorders are discussed. Am. J. Med. Genet. 74:432–438, 1997. © 1997 Wiley-Liss, Inc.     

A rare course of Whipple's disease with atypical cardiac manifestation

Whipple's disease (WD) is a rare disorder caused by the gram-positive actinomycete Tropheryma whippelii (1). An oral route of acquisition is presumed (2). WD is a chronic systemic infection morphologically characterized by foamy PAS-positive macrophages. This case report depicts the diagnosis and clinical management of a woman who presented with atypical cardial manifestations of WD and died from severe cardiac impairment by Tropheryma whippelii which was confirmed by polymerase chain reaction. Histological assessment of myocardial specimens obtained at autopsy showed PAS-positive macrophages accumulating within foci of interstitial myocardial fibrosis. Immunohistochemical staining demonstrated myocarditis with lymphocytes and neutrophilic granulocytes, which has not been reported so far in the course of WD.     

Modified Cognitive Behavior Therapy for Severe,Treatment‐Resistant Obsessive‐Compulsive Disorder in an Adolescent With Autism Spectrum Disorder

There is a high rate of comorbidity between obsessive‐compulsive disorder (OCD) and autism spectrum disorders (ASD). Standard cognitive‐behavior therapy (CBT) protocols have been shown to be less effective in treating OCD in young people with ASD than in typically developing youth. This case study describes the treatment of an adolescent boy with severe, treatment‐resistant OCD and ASD using a modified CBT approach. Modifications to a standard evidence‐based CBT for OCD protocol included extended psychoeducation about anxiety; regular home‐based sessions; and increased involvement of systems, including family and school. Multi‐informant outcome data indicated significant improvements in OCD symptoms over the course of treatment with gains being maintained over a 12‐month follow‐up period. These findings demonstrate the potential efficacy of modified CBT for pediatric OCD in the context of ASD.     

Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder

BACKGROUND: To investigate the prevalence and correlations of suicidal behavior in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients. METHODS: A total of 348 adolescents, representing consecutive admissions to an adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had an eating disorder. In addition, 87 normal community controls were assessed. All subjects were assessed for suicidal behavior by the Childhood Suicide Potential Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and for aggression by the Yudowsky Overt Aggression Scale. RESULTS: All the psychiatrically ill subjects, including those with OCD, had high levels of depression, anxiety and impulsiveness, which were far higher than those of the controls. The rate of attempted suicide was, however, much lower in the OCD subjects. In addition, there was a significant inverse correlation between suicidal behavior levels on the CSPS and depression in the OCD subjects, while all other subjects showed the expected significant positive correlation between level of suicidal behavior and depression. LIMITATIONS: This study looked at a referred population and generalization to outpatient and community samples cannot be made. Distinguishing between the primary and the comorbid diagnosis is difficult and some findings are based on small sample size and therefore may be vulnerable to type I error. CONCLUSIONS: Although suicidal ideation and depressive symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other psychiatrically ill adolescents.     

Attention-Deficit Hyperactivity and Obsessive-Compulsive Symptoms in Adult Patients With Primary Restless Legs Syndrome: Different Phenotypes of the Same Disease?

Objectives: To investigate the prevalence of attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) symptoms in adult patients with primary restless legs syndrome (RLS) and to determine the iron biological correlates of these comorbidities. Participants and Methods: We obtained demographic and clinical data from consecutive 105 outpatients with idiopathic RLS who answered validated questionnaires designed to assess the presence of ADHD and OCD symptoms. In these patients, iron blood parameters were routinely checked. Results: Of the total sample, 42.86% of the patients with RLS showed symptoms reminiscent either of ADHD or OCD. Prevalence of ADHD and OCD symptoms was 27.62% and 7.62%, respectively. Compared to other groups, a significantly higher percentage of RLS patients with ADHD symptoms was on antidepressant (p = 0.012); and women with ADHD symptoms, either alone or combined with OCD symptoms, showed significant reduced ferritin concentrations compared to men with either isolated ADHD symptoms or with combined ADHD and OCD symptoms (p = 0.028 and p = 0.025, respectively). Conclusions: Our findings highlight the high prevalence of ADHD and OCD symptoms in adult patients with primary RLS and independently of serum iron stores decrease, except for women with ADHD symptoms either alone or in combination with OCD symptoms. This may suggest an overlapping neurobiological dopaminergic and serotoninergic dysfunction in ADHD, OCD, and RLS, and question the expression of different RLS phenotypes. The efficacy of dopamine agonists in these groups of patients should be questioned in future studies.     

Cognitive-behavioral therapy for children who have obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a relatively chronic and impairing disorder in children and adolescents. Whereas childhood OCD was largely ignored in the past, major advances in the identification and treatment over the past 20 years have led to a significant upsurge in the prevalence of youngsters seeking treatment for this problem. The present article describes the use of exposure-based cognitive-behavioral therapy (CBT) for the treatment of childhood OCD. Although the phenomenology of OCD is largely consistent across the age span, traditional adult CBT approaches have been modified for use with children and adolescents in order to address those developmental differences that do exist. The case example describes the use of CBT for a child who has OCD and highlights these developmental considerations, including age-appropriate techniques to address family involvement in the disorder and the impact of symptoms on the psychosocial functioning of the patient.     

Does SSRI augmentation with antidepressants that influence noradrenergic function resolve depression in obsessive-compulsive disorder?

BACKGROUND: Obsessive compulsive disorder (OCD) often coexists with major depressive disorder (MDD). Serotonergic antidepressant medications have emerged as the treatment of choice for both OCD and MDD. In the usual course of events, both the patient's OCD and depressive symptoms improve in parallel following initiation of serotonin reuptake inhibitor (SRI) treatment for OCD. However, such is not always the case. We report here on a series of ten patients whose OCD but not depression improved following a trial of SRI therapy. METHOD: Ten patients with OCD and comorbid MDD who experienced a worsening or exacerbation of depressive symptoms while being maintained on an adequate dose of SRI therapy were treated using a combination of SRIs and agents with effects on noradrenergic reuptake. Response to treatment was based on clinician-ratings of severity and improvement of OCD and MDD (CGI-S and CGI-I). RESULTS: Following augmentation, nine of the ten patients had a significant improvement/resolution of their MDD, with little further change in the severity of their OCD. LIMITATIONS: Inferences from the results of this study are limited by the lack of a control group, the small sample size, and the use of nonstandardized ratings as measures of symptom severity. CONCLUSIONS: These results are of practical significance to clinicians insofar as they suggest a possible guideline to clinicians treating depression in OCD with SSRIs without success.     

The familial association of tourette's disorder and ADHD: The impact of OCD symptoms

Tourette's 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. © 2011 Wiley‐Liss, Inc.     

Do antipsychotics ameliorate or exacerbate Obsessive Compulsive Disorder symptoms? A systematic review

BACKGROUND: Paradoxically, some reports in the literature support the use of antipsychotics in the treatment of Obsessive Compulsive Disorder (OCD), while other reports suggest that antipsychotics can exacerbate OCD symptoms. To date, there is no published systematic review of the relationship between OCD symptoms and antipsychotic drugs. METHODS: A Medline and PsychInfo search (1980-2003) was conducted to collect published reports of the interactions between antipsychotics and OCD symptoms. RESULTS: In the treatment of refractory OCD, case series, open label trials and placebo-controlled trials were found suggesting efficacy of antipsychotic augmentation to ongoing antidepressant treatment. In the placebo-controlled trials with haloperidol, risperidone, olanzapine, and quetiapine, a significantly higher response rate (46-71%) was found for the antipsychotic groups, compared to no response for the placebo groups. Reports of exacerbation of OCD symptoms with the use of atypical antipsychotics were limited to individuals with a primary psychotic disorder. LIMITATIONS: Definition of response in most of these treatment studies was based on a modest reduction of OCD symptoms, and no studies were available on long-term efficacy. There were also no published reports that systematically evaluated the incidence of OCD symptoms associated with atypical antipsychotics. CONCLUSIONS: All antipsychotics mentioned above had short-term controlled evidence to support their use as augmenting agents in the treatment of refractory OCD. The suggested management of OCD induction/exacerbation due to atypical antipsychotics is to increase the dose of the atypical antipsychotic and/or add a selective serotonin reuptake inhibitor.     

Symptom Dimension Response in Children and Adolescents with Obsessive-Compulsive Disorder

This report examined the nature of obsessive-compulsive disorder (OCD) symptoms nominated for treatment and investigate improvement in OCD symptom dimensions. Youth with OCD (N = 71) participated in a clinical trial that compared exposure-based cognitive behavior therapy (CBT) to psychoeducation plus relaxation training (PRT). Participants completed a baseline assessment to characterize OCD severity. Next, parents and youth collaboratively developed an OCD symptom treatment hierarchy. Afterward, these symptoms were independently reassessed at each session by youth and parents. After 12 sessions, a posttreatment assessment was completed by independent evaluators. A greater incidence of baseline aggressive/checking symptoms predicted a positive CBT treatment response. For parent ratings of youth distress, CBT outperformed PRT across symptom dimensions, but hoarding symptoms exhibited a slower rate of improvement relative to other dimensions across treatments. For youth distress ratings, CBT outperformed PRT across most symptom dimensions. Although symmetry/ordering symptoms exhibited a slower rate of improvement relative to other dimensions across treatments, post hoc tests found no difference in the average distress rating for symmetry/ordering symptoms between treatment groups. Finally, across symptom dimensions, parents reported a linear reduction in youth distress, whereas youth experienced a nonlinear reduction in distress that diminished over treatment. Exposure-based CBT is beneficial for OCD symptoms and remains the principle treatment for pediatric OCD. However, as symmetry/ordering symptoms exhibited improvement from CBT and PRT, there is some shared treatment mechanisms that improves these symptoms. Finally, as youth perceive diminishing distress reduction over time, clinicians are encouraged to employ appropriate reinforcement strategies in treatment.     

Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical phenotype of the disease is varied. It is proposed that this variation may be a result of differential functional disruption of ATPase7B (ATP7B) resulting from mutations in the gene ATP7B. We aimed to assess the relationship between specific mutational defects in ATP7B and divergence in the phenotypic expression of WD. One hundred and forty-two patients with clinically, biochemically and genetically diagnosed WD were included in the study. The phenotypic expression of WD was compared between patients with different types of mutations in ATP7B, detected by direct sequencing of exons 1-21 of the gene. Twenty-six mutations were identified in ATP7B; eleven of them were mutations predicted to result in the absence of a full-length normal protein [frameshift/nonsense mutations; classified as 'severe' mutations (SMs)], 14 were missense mutations (MMs) and one was a splice site mutation. Patients with one or two SMs on their alleles had lower serum copper and ceruloplasmin and were younger when the first symptoms of the disease appeared, compared with individuals with two MMs. The effect of SMs on the WD phenotype was dose-dependent. It is concluded that mutations within ATP7B are very heterogeneous. Frameshift and nonsense mutations are associated with a severe phenotype of WD.     

The erring brain: Error‐related negativity as an endophenotype for OCD—A review and meta‐analysis

Obsessive‐compulsive disorder (OCD) is a complex and heterogeneous disorder that is associated with high personal and societal costs. Feelings of doubt, worry, and repetitive behavior, key symptoms of OCD, have been linked to hyperactive error signals in the brain. The error‐related negativity (ERN) represents a validated marker of error processing in the ERP. Increased ERN amplitudes in OCD have been reported very robustly over the last 20 years. This article integrates results from 38 studies analyzing the ERN in OCD, using a quantitative meta‐analysis. Meta‐regressions were used to examine potential moderators such as task type, symptom severity, age, and sample size. The meta‐analysis reveals a robust increase of ERN in OCD patients compared to healthy participants in response‐conflict tasks (SMD ?0.55) that is not modulated by symptom severity and age. No increase in ERN in OCD was observed in tasks that do not induce response conflict (SMD ?0.10). In addition to the meta‐analysis, the current article reviews evidence supporting that increased ERN amplitudes in OCD fulfill central criteria for an endophenotype. Further, the specificity of increased ERN amplitudes for OCD and its suitability as a potential transdiagnostic endophenotype is discussed. Finally, the clinical utility and clinical applications are examined. Overall, the evidence that increased ERN amplitudes represent a promising endophenotype indicating vulnerability for OCD is compelling. Furthermore, alterations in ERN are not limited to OCD and may constitute a transdiagnostic endophenotype. Altered neural error signals might serve as a diagnostic or predictive marker and represent a promising target for interventions.     

The great mimicker: a rare presentation of Whipple's disease diagnosed on a gastric biopsy

A 60-year-old gentleman presented with chronic diarrhoea and weight loss. Following an array of investigations, primarily targeting a possible malignancy, gastritis and duodenitis were observed on endoscopy. Gastric and duodenal biopsies showed aggregates of PAS positive macrophages in the lamina propria. Polymerase chain reaction confirmed the presence of Whipple's disease (WD). WD is a rare multisystemic granulomatous infectious disorder, affecting many organ systems but predominantly the gastrointestinal system. WD has a two stage process. The prodromal stage is dominated by arthralgia and arthritis, followed by a latency period, from one to ten years and then by a later steady-state stage which is characterized by the involved organ systems. WD can be fatal if left untreated, however a strict antibiotic regime may eradicate the causative organism, Tropheryma whipplei. We report a rare case of WD diagnosed on a gastric biopsy with an agglomeration of misleading signs and symptoms which demonstrate the mimicry of this potential infectious disease.     

Family accommodation in pediatric obsessive-compulsive disorder.

Despite the importance of the family in the treatment of pediatric obsessive-compulsive disorder (OCD), relatively little empirical attention has been directed to family accommodation of symptoms. This study examined the relations among family accommodation, OCD symptom severity, functional impairment, and internalizing and externalizing behavior problems in a sample of 57 clinic-referred youth 7 to 17 years old (M = 12.99 +/- 2.54) with OCD. Family accommodation was a frequent event across families. Family accommodation was positively related to symptom severity, parent-rated functional impairment (but not child-rated impairment), and externalizing and internalizing behavior problems. Family accommodation mediated the relation between symptom severity and parent-rated functional impairment.     

肝豆状核变性基因表达产物及基因突变的研究

目的 探讨肝豆状核变性（Wilson's disease,WD)的发病机理。方法 将活检获得的WD患者肝标本体外分离,培养肝细胞,应用Western印迹法对WD患者肝细胞WD蛋白进行检测,同时扩增其基因组DNA并直接测序。结果 3例WD患者中有2例出现肝细胞WD蛋白特异条带密度降低。DNA测序发现其中一例患者存在ATP7B778位点CGG→CTG（Arg778Leu)杂合突变及770位点CTC→CTG改变。结论 WD基因在WD患者肝细胞的蛋白表达存在异常。可能与ATP7B基因突变有关。     

Association of the tumor necrosis factor ‐308 A/G promoter polymorphism with Tourette syndrome

Several lines of evidence suggest that certain subtypes of obsessive‐compulsive and tic disorders might be paediatric manifestations of post‐streptococcal autoimmunity caused by cross‐reactive autoantibodies. As tumor necrosis factor (TNF) is known to play a seminal role in coordinating the humoral immune response, TNF gene polymorphisms have been proposed as genetic risk factors both in obsessive‐compulsive disorder (OCD) and Tourette syndrome (TS). The aim of this study was to investigate two TNF promoter polymorphisms (‐238 A/G: rs361525 and ‐308 A/G: rs1800629) on the genetic susceptibility to OCD and TS in a child psychiatric sample (102 patients with OCD and 117 patients with TS). In the case–control set‐up, the genotype and allele frequencies were compared to a control group from the general population (n = 405). As a control child psychiatric sample, 194 children with attention‐deficit hyperactivity disorder were also genotyped. Our results revealed that the TNF ‐308 G‐allele was more frequent in children with TS compared to controls (90.2% vs 84.8%, P = 0.037). For confirmation of this genetic association, a family‐based analysis, the transmission disequilibrium test was used, which showed preferential transmission of the G‐allele to patients with TS (nominal P‐value 0.011). Moreover, this allele was also transmitted more frequently to children with tic symptoms (nominal P‐value 0.039). No association was found between OCD or obsessive‐compulsive symptoms and the studied TNF polymorphisms. Based on these findings, the TNF ‐308 G‐allele can be associated with Tourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.     

Anxiety disorders and control related beliefs: the exemplar of Obsessive-Compulsive Disorder (OCD)

Beliefs about control have been postulated to be important to anxiety and mood disorders. In particular, the phenomenology of Obsessive-Compulsive Disorder (OCD) suggests that it may be an exemplar of an anxiety disorder where control issues related to the self (behavior and thoughts) and world (the external environment) are particularly important. However, only beliefs concerning the need to control thoughts have been incorporated into contemporary theories of OCD. This article summarizes the theoretical and empirical research relevant to control-related beliefs in OCD. It is suggested that discrepancies between an individual's desired level of control and their perceived level of control could contribute to OCD symptoms, and exacerbate the tendency for individuals with OCD to engage in magical ideation and superstitious rituals. Overall, this review demonstrates how consideration of control cognitions could enhance our understanding of OCD and further improve its treatment.