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PubMed2000

A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder.

BACKGROUND: To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone. METHODS: Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition. RESULTS: For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated. CONCLUSION: These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.

Adult↗
PubMed2004

Mapping structural brain alterations in obsessive-compulsive disorder.

BACKGROUND: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process.

Adolescent↗
PubMed2005

Frontal-striatal dysfunction during planning in obsessive-compulsive disorder.

BACKGROUND: Dysfunction of frontal-striatal, particularly orbitofrontal-striatal, circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD), characterized by obsessions, ritualistic behavior, anxiety, and specific cognitive impairments. In addition, neuropsychological studies in OCD have reported impairments in visuospatial tasks and executive functions, such as planning. OBJECTIVE: To determine whether dorsal prefrontal-striatal dysfunction mediates planning impairment in patients with OCD. DESIGN: A parametric self-paced pseudorandomized event-related functional magnetic resonance imaging version of the Tower of London task was used in 22 medication-free patients with OCD and 22 healthy control subjects. This paradigm, allowing flexible responding and post hoc classification of correct responses, was developed to compare groups likely to differ in performance. RESULTS: Behavioral results showed significant planning impairments in OCD patients compared with control subjects. During planning, decreased frontal-striatal responsiveness was found in OCD patients, mainly in dorsolateral prefrontal cortex and caudate nucleus. In addition, OCD patients showed increased, presumably compensatory, involvement of brain areas known to play a role in performance monitoring and short-term memory processing, such as anterior cingulate, ventrolateral prefrontal, and parahippocampal cortices. CONCLUSIONS: These findings support the hypothesis that decreased dorsal prefrontal-striatal responsiveness is associated with impaired planning capacity in OCD patients. Because the described frontal-striatal dysfunction in OCD is independent of state anxiety and disease symptom severity, we conclude that executive impairment is a core feature in OCD.

Adult↗
PubMed2006

Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder.

CONTEXT: There is strong evidence from family and twin studies that genetic determinants play an important role in the etiology of obsessive-compulsive disorder (OCD). In the only genome scan of OCD to date that we are aware of, suggestive linkage was reported to the chromosomal region 9p24, a finding that was subsequently replicated. This region contains the gene encoding the neuronal glutamate transporter, SLC1A1. SLC1A1 represents an excellent candidate gene for OCD based on evidence from neuroimaging and animal studies that altered glutamatergic neurotransmission is implicated in the pathogenesis of this disorder. OBJECTIVE: To determine whether sequence variants in SLC1A1 are associated with transmission of the OCD trait. DESIGN: A family-based candidate gene association study. SETTING: A specialized anxiety disorders outpatient clinic. PARTICIPANTS: One hundred fifty-seven white probands with DSM-IV OCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total). INTERVENTION: Nine single nucleotide polymorphisms spanning SLC1A1 were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined included DSM-IV OCD diagnosis and highest lifetime symptom severity as measured using the Yale-Brown Obsessive-Compulsive Scale. Correction for multiple comparisons was performed using permutation tests. RESULTS: After correction for multiple comparisons, 2 variants, rs301434 (chi 2 = 12.04; P = .006) and rs301435 (chi 2 = 9.24; P = .03), located within a single haplotype block were found to be associated with transmission of OCD. Furthermore, a specific 2-marker haplotype within this block was significantly associated with OCD (chi 2 = 12.60; P = .005). This haplotype association was statistically significant in transmissions to male but not female offspring. CONCLUSIONS: Although requiring replication in larger samples, these findings provide preliminary evidence that sequence variation in SLC1A1 is associated with susceptibility to OCD, particularly in males. Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.

Adolescent↗
PubMed2004

Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial.

CONTEXT: The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. OBJECTIVE: To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. DESIGN, SETTING, AND PARTICIPANTS: The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. INTERVENTIONS: Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. MAIN OUTCOME MEASURES: Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. RESULTS: Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. CONCLUSION: Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.

Adolescent↗
PubMed1997

Episodic and chronic obsessive-compulsive disorder.

Several lines of evidence support the concept of obsessive-compulsive disorder (OCD) as a heterogeneous illness. Using a range of factors such as demographic, psychosocial, and clinical variables, we compared OCD patients with chronic (n = 55) versus episodic (n = 46) courses of illness. Patients were evaluated monthly for 1 year while receiving no treatment. Significant differences in sex ratio, age at onset of the disorder, illness duration, type of symptoms, and familial history were found between the two groups. These findings are consistent with the concept of OCD as a heterogeneous disorder. Patients with an episodic course of the disorder may be a distinct subgroup within the whole group of obsessive-compulsive patients.

Acute Disease↗
PubMedDate not supplied

Pregnancy complicated by obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a well-recognized psychiatric disorder often beginning in reproductive age. A case of OCD in pregnancy is presented and its management discussed. A 28-year-old G3P2 woman presented at 8 weeks' gestation for prenatal care. She had been diagnosed with OCD following her prior pregnancy. Her symptoms primarily involved obsessions about infectious disease and compulsive cleaning and organization of household items, both of which greatly distressed her and interfered with caring for her children. She had been managed with clomipramine between pregnancies and was beginning a clinical trial of fluvoxamine when pregnancy was diagnosed. She discontinued medication when she realized she was pregnant. Her symptoms were managed during the pregnancy with frequent appointments with her obstetrician and her psychiatrist. She used a behavioral technique, "thought-stopping", as well. Her symptoms worsened in the last month of pregnancy and immediately after delivery; she delivered a normal infant. The clomipramine was restarted postpartum. She has done well since then, with minimal psychiatric symptoms. OCD is a disabling psychiatric disorder that occurs in women of reproductive age. With careful management, pregnancy without disabling psychiatric symptoms can occur.

Adult↗
PubMed1996

What predicts improvement and compliance during the behavioral treatment of obsessive compulsive disorder?

The aim of the study was to identify factors associated with treatment compliance and clinical improvement when obsessive compulsive disorder is treated with graded exposure and response prevention. The sample consisted of all patients with a diagnosis of obsessive compulsive disorder admitted over a 3-year period to a unit specialising in behavioral treatment. All subjects were diagnosed using reliable diagnostic criteria and all were followed-up for 12 months. A range of social and clinical variables was examined using stepwise regression analysis. Treatment compliance was associated with being employed during treatment and living with one's family. Clinical improvement was associated with never having been treated previously, being employed during treatment, having a fear of contamination, having overt ritualistic behaviour, the absence of depression and living with one's family.

Adolescent↗
PubMed1983

Assessing the impact of cognitive differences in the treatment of obsessive-compulsives.

Demonstrated a set of research techniques that combine multidimensional scaling, a quantitative cognitive procedure, and cost outcome analysis. The multidimensional scaling results supported Reed's (1969) notion that obsessive-compulsive clients are underinclusive and did not support Foa and Steketee's (1979) contention that they are overinclusive. Significant differences in extent of follow-up therapy were found between obsessive compulsives (N = 12) with the underinclusive cognitive style and those with a normal cognitive style.

Adult↗
PubMed1991

Obsessive-compulsiveness in obese weight-loss patients and normal weight adults.

It recently has been suggested that obsessive-compulsive personality characteristics may predispose people to become obese. In addition, it has been suggested that dieting may increase the frequency of thoughts about food and its consumption. The present study compared a group of 50 obese weight-loss patients to 50 normal weight adults on personality-related O-C characteristics and food and eating-related cognitions. Results supported the notion that obese weight-loss patients tend to be obsessed with food. There was no evidence that traditional O-C personality measures are related to obesity. These results suggest that effortful inhibition of appetitive behaviors may have adverse cognitive consequences.

Adult↗
PubMed1995

Compulsive eating, obsessive thoughts of food, and their relation to assertiveness and depression in women.

Fifty-three self-defined compulsive eaters recruited from weight loss programs and a college population and prescreened to eliminate probable anorexics and bulimics participated in this study. They completed the Three Factor Eating Questionnaire, Beck Depression Inventory, Compulsive Eating Scale, Eating Obsessive-Compulsive Questionnaire, Personal Assertion Analysis, and provided demographic information. Participants had high scores for compulsive eating and disinhibition and low scores for depression. The best predictors of compulsive eating were disinhibition and obsessive thoughts of food, which accounted for 61% of the variance. Twenty-one percent of the sample reported a history of sexual abuse. Thirty-one percent of the sample were classified as medically obese, yet 49% perceived themselves to be moderately to very overweight.

Adolescent↗
PubMed1993

History of eating disorders in female patients with obsessive-compulsive disorder.

The prevalence of eating disorders was assessed in a casenote study of 105 female patients with obsessive-compulsive disorder (OCD). A previous history of anorexia nervosa was found in 12 (11%). Patients with a previous history of eating disorders (OCD-AN) had an earlier onset of OC symptoms than other patients. Among OCD-AN patients, the anorexia nervosa and obsessive-compulsive disorders had a similar age of onset. The comorbidity of the two syndromes among females may point to common vulnerability factors. Patients with early onset OCD may be at increased risk of developing eating disorders. The assessment of OCD in young female patients should include a careful check for evidence of eating disorders.

Adult↗
PubMed2000

Acute onset and remission of obsessions and compulsions following medical illnesses and stress.

Obsessive Compulsive Disorder (OCD) is generally chronic. Episodic OCD with complete remission has been rarely reported. Two cases of brief, episodic obsessions and compulsions that appeared for the first time following psychological stress and in the context of medical illness are reported. The possibility of brief episodes of OCD precipitated by stress is illustrated. Exploration of this phenomenon may help us learn more about OCD in general.

Acute Disease↗
PubMed2003

Cytogenetic analysis of obsessive-compulsive disorder (OCD): identification of a FRAXE fragile site.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disease characterized by recurrent obsessions, compulsions, or both. The prevalence rate of OCD is 2.1% in the general population. Here we report cytogenetic analysis of 26 patients affected with OCD. In one male patient (OCD-K33), we identified a fragile X chromosome by cytogenetic analysis with 21% of cells demonstrating a fragile site at Xq27-q28. Polymerase chain reaction (PCR) and Southern blot analysis demonstrated that the molecular basis of the OCD-K33 fragile X chromosome was expansion of the CCG repeat at FRAXE. The number of the expanded repeats was estimated to be more than 300 copies, qualifying it as a full FRAXE mutation. Further analysis of the family members of OCD-K33 revealed another member with a full FRAXE mutation (630-1,200 copies of the CCG repeat), who had the clinical phenotype of speech impairment, and two other members with normal phenotypes and no FRAXE expansion. The two FRAXE expansions lead to complete methylation at the CCG repeat. The co-segregation of the full FRAXE mutation with apparent neurologic disorders in the same family provides further support to the notion that FRAXE is a genetic neurologic condition. Our findings expand the spectrum of clinical phenotypes associated with FRAXE mutations.

Chromosomes, Human, X↗
PubMed2004

Mu opioid receptor gene as a candidate for the study of obsessive compulsive disorder with and without tics.

Obsessive compulsive disorder (OCD) is a complex psychiatric disease characterized by recurring obsessions or compulsions that cause significant distress to the patient. The etiology of this disorder remains largely unknown, although a genetic component has been suggested. Many candidates genes have been evaluated based on a possible serotoninergic and dopaminergic brain dysfunction. We postulate the micro opioid receptor (MOR) gene as a candidate because some observations support a role of the opioid system in OCD. The opioid antagonist, naloxone, rapidly exacerbates OCD symptoms and the opioid agonist, tramadol, was reported to be effective in the treatment of some patients. We studied two single nucleotide polymorphisms (C17T and A118G) in 51 trios with OCD. Genotyping was analyzed with transmission desequilibrium test (TDT). The allelic variant +17T of the C17T polymorphism had a low frequency (1%) in our population that did not allow for statistic analysis. However, for the allelic variant +G of the A118G polymorphism we were able to performed statistical comparisons. Our results showed a trend toward significance (chi(2) McNemar = 3.6, P = 0.065) for TDT in patients with comorbid tics. It is an interesting finding that should be tested in a larger sample of OCD patients with tics.

Adult↗
PubMed2004

Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted.

Adult↗
PubMed2005

Evidence for the gamma-amino-butyric acid type B receptor 1 (GABBR1) gene as a susceptibility factor in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a well-recognized severe neuropsychiatric illness. Genetic factors are believed to be important etiologically. Although historically genetic testing has focused on the serotonergic and dopaminergic systems, there is increasing evidence that the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), may also be functionally involved. Furthermore the GABA type B receptor 1 (GABBR1) gene has been localized to chromosome 6p21.3 region, which has shown linkage to OCD. We investigated five polymorphisms (A-7265G substitution; C10497G substitution; A33795G substitution in the 3'-UTR; Ser-491-Ser-T1473C transition; Phe-659-Phe-T1977C transition) in the GABBR1 gene in a sample of 159 DSM-IV OCD probands and their families, using the transmission disequilibrium test (TDT). A trend was observed with an over-transmission of -7265A allele at the A-7265G polymorphism and OCD (chi2 = 3.270, P = 0.071). Moreover, the TDT haplotype analysis using TRANSMIT showed a trend toward association with the haplotype of the five polymorphisms together [2.1.1.2.1 (A-7265G.C10497G.Ser-491-Ser.Phe-659-Phe.A33795G)] with a Chi-square value of 3.418, which corresponds to a P-value of 0.065 (overall chi2 = 6.353, 5 df, P = 0.273). Moreover, a trend was observed for the total Yale-Brown obsessive-compulsive scale score in the A-7265G polymorphism (-7265A: z = 1.934, P = 0.053) using the Family-Based Association Test, considering the diagnosis of OCD and then the clinically relevant quantitative phenotypes. The observed trends suggest that further investigations of the role of the GABBR1 gene in OCD are warranted.

Adult↗
PubMed2001

Social functioning and quality of life comparisons between obsessive-compulsive and schizophrenic disorders.

Treatment of obsessive-compulsive disorder has focused almost exclusively on symptom reduction; however, deficits in social functioning and quality of life of individuals with this disorder may contribute more to their "burden," suffering, and disability. To gauge the significance of social dysfunction and quality of life of persons with obsessive-compulsive disorder (OCD), we made comparisons with a group of persons with schizophrenia matched for age and gender. Thirty-one patients with OCD participating in a partial hospital treatment program were compared with 68 schizophrenic outpatients participating in a day rehabilitation program. The Independent Living Skills Survey (ILSS) and Lehman Quality of Life Scale (QOL) were administered before and after treatment for both cohorts. QOL scores were significantly lower for the OCD patients both before and after treatment, but improved significantly during treatment. OCD and schizophrenic patients had similar scores on almost every domain of the ILSS at pretreatment. The OCD patients improved significantly on many of the domains of social and independent living skills as a result of treatment and acquired significantly greater skills by post-treatment than did their counterparts with schizophrenia; however, the performance of social and independent living skills by OCD patients remained less than satisfactory even in domains where they improved. In the areas of job and leisure skills, there were significant group-by-time interactions. We concluded that patients with severe OCD and patients with schizophrenia are equally socially impaired. However, OCD patients experience greater significant functional improvement with multimodal treatment.

Activities of Daily Living↗