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PubMed2004

Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 ( alpha =0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P=.006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P=.046 and .02, respectively) for association.

Chromosome Mapping↗
PubMed2002

Case series: Adderall augmentation of serotonin reuptake inhibitors in childhood-onset obsessive compulsive disorder.

Current pharmacological treatment of obsessive compulsive disorder involves the use of selective serotonin reuptake inhibitors (SSRIs). However, a large proportion of patients does not respond fully to these medications despite receiving optimal doses and concomitant cognitive-behavioral therapy. Finding efficacious augmentation strategies has become an important goal of researchers and clinicians working with this population. In this case series, we describe four patients with childhood-onset obsessive compulsive disorder, and with partial or no response to SSRI treatment, who subsequently had a reduction of their symptoms with Adderall augmentation.

Adult↗
PubMed2003

Impact of comorbidity on treatment response to paroxetine in pediatric obsessive-compulsive disorder: is the use of exclusion criteria empirically supported in randomized clinical trials?

OBJECTIVE: To examine the influence of psychiatric comorbidity on response and relapse rates in children and adolescents treated with paroxetine for obsessive-compulsive disorder (OCD). METHODS: Patients responding following 16 weeks of treatment (phase I) were randomized to continued paroxetine or to placebo for 16 additional weeks (phase II). OCD response (phase I) and relapse (phase II) criteria were based on the Clinical Global Impression-Improvement Scale and the Children's Yale-Brown Obsessive Compulsive Scale. The presence of OCD and other psychiatric disorders was ascertained using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview. RESULTS: At entry, 193 of 335 (57.6%) patients had at least one psychiatric disorder in addition to OCD, and 102 of 335 (30.4%) had multiple other disorders. Although the response rate to paroxetine in the overall population was high (71%), the response rates in patients with comorbid attention deficit hyperactivity disorder, tic disorder, or oppositional defiant disorder (56%, 53%, and 39%, respectively) were significantly less than in patients with OCD only (75%) (intent-to-treat population, last observation carried forward analysis, p < 0.05). Psychiatric comorbidity was associated with a greater rate of relapse in the total patient population (46% for one or more comorbid disorders [p = 0.04] and 56% for two or more comorbid disorders [p < 0.05] vs. 32% for no comorbidity). CONCLUSIONS: The results of these post hoc analyses show that comorbid illness adversely impacted response to pharmacotherapy with paroxetine in pediatric OCD and significantly increased risk of relapse following withdrawal from treatment. Continued paroxetine treatment reduced the relapse rates in all groups compared with placebo, including those with comorbid illness. Because pediatric OCD is frequently comorbid with other psychiatric disorders, results of randomized, controlled pediatric OCD trials that use multiple exclusion criteria may not generalize to more naturalistic OCD samples.

Adolescent↗
PubMed2003

Remission status after long-term sertraline treatment of pediatric obsessive-compulsive disorder.

BACKGROUND: Despite its high chronicity, few studies have evaluated the effectiveness of long-term treatment for pediatric obsessive-compulsive disorder (OCD). The goal of the current analysis is to evaluate remission among children and adolescents with OCD treated with sertraline for 12 months. METHODS: Children (6-12 years old, n = 72) and adolescents (13-18 years old, n = 65) with Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) OCD, who had completed a 12-week, double-blind, placebo-controlled sertraline study, were administered open-label sertraline 50-200 mg for 52 weeks. Full remission was defined by a Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score of 8 or less, and partial remission was defined as a CY-BOCS score of 15 or less. RESULTS: Using an last observation carried forward analysis, 47% of patients achieved a full remission, and an additional 25% achieved a partial remission. Among study completers, full remission was achieved by 55% of patients and partial remission by 31%. Two thirds of patients with severe OCD at baseline (CY-BOCS of 26 or greater) achieved full or partial remission. Children were more likely to achieve a full remission than adolescents. CONCLUSION: Sertraline is effective in the treatment of childhood and adolescent OCD, with initial acute response converting to remission and improved functional status in a substantial proportion of patients. More research is needed to develop pharmacologic and psychotherapeutic strategies that facilitate the achievement of full remission in the remaining patients suffering from this chronic and disabling illness.

Adolescent↗
PubMed1996

Behavioral therapy in children and adolescents with obsessive-compulsive disorder: a pilot study.

Despite advances in pharmacotherapy for obsessive-compulsive disorder (OCD), medication treatments are not always effective. This pilot project examined the feasibility of a structured behavioral therapy program in the treatment of children and adolescents with OCD. Ten subjects with a primary diagnosis of OCD were invited to participate in the treatment program. Seven youngsters, 5 boys and 2 girls (age range 10.8-15.8, mean 13.0 years), participated and were treated for a mean of 14 sessions. These 7 subjects showed a broad range of OCD severity, as measured by the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS score range 12-29). Five subjects were also receiving antiobsessional medication (dose was not changed during the trial), and 2 subjects were treated without medication. All 7 youngsters showed a clinically significant reduction in the CYBOCS score at treatment endpoint (mean change 61%, range 30%-90%, effect size 2.04, p < 0.05), and the therapeutic gains were stable for at least 3 months after treatment. One of 5 children who had been receiving concurrent antiobsessional medication was able to tolerate a dose reduction following behavioral treatment. Two to three booster sessions within 6 months posttreatment were effective in preventing relapse in 4 of 6 subjects. The 3 children who declined behavioral treatment showed no improvement at 3-month and 6-month follow-up. Behavioral treatment appeared to be a useful adjunct to medication in children and adolescents with OCD. Further research could evaluate whether behavioral treatment would lower the dose requirements for children receiving antiobsessional medications. Randomized clinical trials are also needed to confirm the effectiveness of behavioral therapy alone or in combination with medication.

1-Naphthylamine↗
PubMed2000

The effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: The efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy. METHODS: Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year. RESULTS: Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two-year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group. CONCLUSIONS: Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS.

Adolescent↗
PubMed2005

Elevated thyroid indices in children and adolescents with obsessive-compulsive disorder: effects of clomipramine treatment.

OBJECTIVE: To examine the basal thyroid function in pediatric Obsessive Compulsive Disorder (OCD) versus controls, and to explore the relation between baseline thyroid measures and response to clomipramine treatment, and the effects of treatment on thyroid hormones. METHODS: Sixteen children and adolescents with DSM-III-R OCE and 13 control children and adolescents without psychiatric illness were compared on basal measures of thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). For the OCD subjects, samples were compared pre- and post- 4 weeks of treatment with clomipramine. Response of OCD symptoms was measured by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). RESULTS: OCD subjects demonstrated subtle but significant elevations of TSH, T3, and T4 pre-treatment compared to controls. Clomipramine treatment was associated with significant decreases in TSH and T3 concentrations. Pre-treatment TSH and T4 concentrations correlated with reductions in CY-BOCS following 8 weeks of clomipramine. CONCLUSION: Elevated thyroid function at baseline may be a biomarker of OCD improvement, and may reflect aspects of the underlying pathophysiology of OCD.

Adolescent↗
PubMed2005

Performance of clinician versus self-report measures to identify obsessive-compulsive disorder in children and adolescents.

OBJECTIVE: The aim of this study was to study agreement between clinician-rated measures and self-report measures previously used in epidemiologic studies to identify obsessive-compulsive disorder (OCD) in youth and to determine the adequacy of self-report measures as screening instruments. METHOD: Leyton Obsessional Inventory-Child Version (LOI-CV) survey form self-report and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) clinician-report measures were compared in a sample of 81 OCD-affected youths diagnosed using structured diagnostic interviews and the best-estimate method. Sensitivities and agreement between tests are determined for different cutoff scores. RESULTS: The LOI-CV survey form total (item+interference) score is correlated with KSADS-E OCD severity (r=0.37, p=0.001) but not clinician-rated GAF scores (r=-0.18, p=0.12). LOI-CV survey form sensitivities at cutoff scores of 15, 20, 25, and 30 are 55%, 36%, 28%, and 19%, respectively. CY-BOCS scores are correlated with subject-rated interview severity (p<0.001) and clinician-rated GAF scores (p or=0.03), but correlate with the CY-BOCS compulsion subscore. CONCLUSIONS: The clinician-rated CY-BOCS measure using parent and child reporting performs superiorly to the subject-rated LOI-CV measure using child reporting to identify pediatric OCD in a clinically referred population. Because self-report measures have been used in epidemiological studies, youth OCD prevalence rates may be higher than previously reported.

Adolescent↗
PubMed1995

Applying the codependency model to a group for families of obsessive-compulsive people.

Obsessive-compulsive disorder places formidable burdens on family members who are drawn into bizarre enabling behaviors to pacify their ill relatives. Some families exhibit a high tolerance for inappropriate behavior and evidence characteristics similar to those seen in families of alcoholics. This article applies the codependency group model to families of obsessive-compulsive people based on a definition of codependency that views these families as normal, feeling people who are trying to cope with unremitting stress. Clinical vignettes illustrate how these families are similar to families of alcoholics in their management of emotions and in their dysfunctional behaviors. Recommendations are offered for practitioners who work with families of mentally ill people.

Adult↗
PubMed1990

Trazodone treatment in clomipramine-resistant obsessive-compulsive disorder.

Trazodone (TZ) was administered to nine patients suffering from obsessive-compulsive disorder (OCD), who failed to respond to either clomipramine (CMI) or to CMI plus lithium carbonate. The group, as a whole, showed significant but mild improvement. Three patients responded very favorably to TZ. In these three responders, efficacy was substantiated by the return of the original obsessive-compulsive (OC) symptoms following TZ withdrawal and their amelioration after its readministration. Interestingly, the aggravation of OCD symptomatology that has been associated with a specific TZ metabolite was not observed. This study is consistent with previous reports of the anti-OC efficacy of TZ and suggests the involvement of complex serotonergic mechanisms in the pathophysiology of this disorder.

Adult↗
PubMed1996

Fluvoxamine treatment in clozapine-induced obsessive-compulsive symptoms in schizophrenic patients.

Interest in the association of obsessive-compulsive (OC) symptoms and schizophrenia has been reawakened since the introduction of clozapine for treatment of schizophrenia. We describe the appearance of this disorder and examine the efficacy of adding fluvoxamine to ongoing clozapine treatment of the OC and schizophrenic symptoms. Four patients with DSM-III-R schizophrenic disorder, in whom OC symptoms appeared during the course of clozapine treatment, are reported. In two patients, fluvoxamine, a serotonin-selective reuptake inhibitor (SSRI), was added to clozapine under open-trial conditions. The patients were serially assessed by using the Brief Psychiatric Rating Scale, Yale-Brown Obsessive-Compulsive Scale, and Scale for the Assessment of Negative Symptoms. The de novo occurrence and eventual spontaneous reduction of OC symptoms were noted in two schizophrenic patients treated with clozapine. In the other two patients, one with previous and the other with a family history of OC disorder, the addition of fluvoxamine to clozapine was effective in eliminating the OC symptoms. A concomitant improvement in the schizophrenic symptomatology was seen as well. It appears that disabling OC symptoms may occur as in response to clozapine treatment in chronic drug-resistant schizophrenic patients. Some of the latter may benefit from the addition of an SSRI to the ongoing clozapine regimen.

Adult↗
PubMed1989

Obsessive-compulsive symptoms in childhood inflammatory bowel disease and cystic fibrosis.

The Leyton Obsessional Inventory-Child Version was administered to 33 children with Crohn's disease, 11 with ulcerative colitis, and 46 with cystic fibrosis. Subjects with ulcerative colitis scored significantly higher on total number of obsessional symptoms and degree of resistance to symptoms than subjects with Crohn's disease. Scores of subjects with cystic fibrosis were intermediate between those of the ulcerative colitis and Crohn's disease groups. However, neither the ulcerative colitis group nor the Crohn's disease group differed significantly from the cystic fibrosis group that were statistically significant. Duration of illness was negatively correlated with symptoms in Crohn's disease and ulcerative colitis. The results suggest that obsessive-compulsive symptoms are not specific to Crohn's disease or ulcerative colitis and that obsessive-compulsive symptoms in pediatric chronic illness may be secondary to the demands of the illness.

Adolescent↗
PubMed1990

Fluoxetine treatment of children and adolescents with Tourette's and obsessive compulsive disorders: preliminary clinical experience.

Fluoxetine hydrochloride is the first selective serotonin uptake inhibitor introduced commercially in the United States. This report describes preliminary clinical experience with fluoxetine in 10 children and adolescents, aged 8 to 15 years, with primary obsessive compulsive disorder (OCD) or Tourette's syndrome (TS) plus OCD. In general, fluoxetine, which was administered from 4 to 20 weeks at a dosage of 10 or 40 mg per day, was well tolerated. Adverse effects included behavioral agitation/activation in four patients and mild gastrointestinal symptoms in two patients. No abnormalities were noted in the seven children who had follow-up EKGs. Five of the 10 patients (50%) were considered responders; their obsessive-compulsive symptoms decreased substantially during treatment with fluoxetine. Responder rates were similar in the primary OCD (two of four, 50%) and TS + OCD (three of six, 50%) groups. In conclusion, short-term fluoxetine administration appears to be safe in children and adolescents. Placebo-controlled trials are needed to further assess the efficacy of fluoxetine.

Adolescent↗
PubMed1990

Psychiatric disorders in first degree relatives of children and adolescents with obsessive compulsive disorder.

One hundred and forty-five first-degree relatives (89 parents [96%] and 56 siblings [98%]) of 46 children and adolescents with severe primary obsessive compulsive disorder (OCD) were personally interviewed with clinical and structured psychiatric interviews. Parent interviews were scored by a rater blind to proband diagnosis. Thirty percent of probands had at least one first-degree relative with OCD: 25% of fathers and 9% of mothers received this diagnosis. Forty-five percent of fathers and 65% of mothers received one or more other psychiatric diagnoses. The increased familial rate of OCD over that expected from a general population, and over that found in parents of conduct disordered patients, is consistent with a genetic factor in OCD. Presenting obsessive compulsive symptoms of probands and their parents were usually dissimilar, arguing against any simple social or cultural transmission.

Adolescent↗
PubMedDate not supplied

Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression.

OBJECTIVE: Fluvoxamine, a monocyclic, specific serotonin uptake inhibitor with demonstrated efficacy in obsessive-compulsive disorder (OCD) and depression in adults, is marketed in more than 30 countries worldwide, including Israel. In the United States, where fluvoxamine is available only on an investigational basis, marketing appears imminent. This study evaluates the safety and efficacy of fluvoxamine in adolescents. METHOD: In an 8-week, open-label trial of fluvoxamine, 20 adolescent inpatients, ages 13 to 18 years, were treated for OCD (n = 14) or major depressive disorder (MDD)(n = 6) with daily doses ranging from 100 to 300 mg. Target symptoms were rated at regular intervals with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Suicide Potential Scales (SPS); Beck Depression Inventory (BDI); the Overt Aggression Scale (OAS); and the Children's Global Adjustment Scale (CGAS). RESULTS: Fluvoxamine proved relatively safe and was especially effective in the patients with OCD; mean Y-BOCS scores decreased significantly (p < .0001) from 28.0 to 19.8 on medication. Although fluvoxamine also appeared effective in decreasing depression and bulimic symptoms, its impact on impulsive, suicidal, and anorectic symptoms was less clear. The commonest side effects (n > or = 3) were dermatitis, insomnia, hyperactivity, excitement, anxiety, tremor, and nausea. Fluvoxamine was discontinued in four patients because of side effects; the most serious side effect occurred in two debilitated anorexic patients, of whom one became delirious and the other developed hallucinations. CONCLUSION: Preliminary evidence suggests that short-term treatment of adolescents with fluvoxamine is relatively safe and may be effective for OCD and some affective spectrum symptoms.

Adolescent↗
PubMedDate not supplied

Obsessive-compulsive disorder and fear of AIDS contamination in childhood.

Two cases of obsessive-compulsive disorder (OCD) in prepubertal children are described in which the predominant obsessive ruminations relate to fear of acquired immune deficiency (AIDS) contamination. The findings in these cases are discussed in relation to known demographic and clinical profiles of OCD in children and adolescents. Fear of AIDS contamination in childhood OCD may reflect the effect of the current emphasis on AIDS in potentially vulnerable children with environmental influences giving the symptoms their specific content.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs) may arise when antibodies directed against invading bacteria cross-react with basal ganglia structures, resulting in exacerbations of obsessive-compulsive disorder (OCD) or tic disorders. This is a report of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci for whom serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAs patients.

Autoantibodies↗
PubMed1996

Platelet serotonin transporter in children and adolescents with obsessive-compulsive disorder or Tourette's syndrome.

UNLABELLED: Previous studies of serotonin transporter protein (5HTPR) indexed in platelets by 3H-imipramine demonstrate reduction in children with comorbid obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). OBJECTIVE: To use the 5HTPR selective ligand 3H-paroxetine and homogeneous diagnostic groups to reevaluate these findings. METHOD: Platelet Kinetic binding parameters were evaluated using standard techniques from medication-free child and adolescent patients with OCD (n = 18), with TS (n = 10), and normal controls (n = 19). RESULTS: Baseline binding capacity (Bmax) was significantly reduced in patients with OCD (1,342 +/- 952 fmol/mg; protein p < .01) compared with normal controls (2,486 +/- 1309 fmol/mg) and TS patients (2,420 +/- 1,069 fmol/mg; p < .05). Among OCD patients who were subsequently treated on an open-label basis with selective serotonin reuptake inhibitor (SSRI), Bmax values at baseline differentiated between responders (1,718 +/- 1,041 fmol/mg) and nonresponders (802 +/- 713 fmol/mg protein; p < .05). Response to SSRI was greatest in patients with a positive family history of OCD. Among responders (n = 10), baseline Yale-Brown Obsessive Compulsive Scale and Bmax were positively correlated (r = .76, p = .01), as was Clinical Global Impression (r = .67, p = .03). CONCLUSIONS: Platelet 5HTPR capacity (Bmax) is reduced in children and adolescents with OCD, but not in those with TS. 5HTPR may be an indirect measure of basal serotonergic tone.

1-Naphthylamine↗