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PubMed2000

A family study of obsessive-compulsive disorder.

BACKGROUND: The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes. METHODS: Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations. RESULTS: The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features. CONCLUSIONS: Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Adolescent↗
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↗
PubMed2005

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study.

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.

Adult↗
PubMedDate not supplied

Uncomplicated and comorbid obsessive-compulsive disorder in an epidemiologic sample.

This study investigated lifetime prevalence rates, demographic characteristics, childhood conduct disorder and adult antisocial features, suicide attempts, and cognitive impairment in individuals with obsessive-compulsive disorder (OCD) uncomplicated by or comorbid with any other psychiatric disorder. The data are from the NIMH Epidemiologic Catchment Area (ECA) study, and the current analyses compared subjects with uncomplicated OCD (no history of any other lifetime psychiatric disorder), comorbid OCD (with any other lifetime disorder), other lifetime psychiatric disorders, and no lifetime psychiatric disorders across these variables. OCD in its uncomplicated and comorbid form had significantly higher rates of childhood conduct symptoms, adult antisocial personality disorder problems, and of suicide attempts than did no or other disorders. Comorbid OCD subjects had higher rates of mild cognitive impairment on the Mini-Mental Status Exam than did subjects with other disorders. These findings suggest that a subgroup of OCD patients may have impulsive features, including childhood conduct disorder symptoms and an increased rate of suicide attempts; wider clinical attention to these outcomes is needed.

Adolescent↗
PubMed2000

Association between homozygosity at the COMT gene locus and obsessive compulsive disorder.

A functional polymorphism in the coding region of the catechol O-methyltransferase (COMT) gene has been reported in previous studies to be associated with obsessive compulsive disorder (OCD), particularly in males [Karayiorgou et al., 1997, 1999]. Using a family-based population analysis, we attempted to replicate these findings in a group of 72 OCD patient/parent trios collected from Buffalo, New York, and Toronto, Canada. Analysis of allele and genotype frequencies using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) did not identify an association between a particular allele and OCD as had been previously reported. Furthermore, no evidence was found to support the findings of a gender-based association for COMT when the patients and the parents of the same gender were compared. However, our genotype results (n = 72) demonstrate a tendency for association between homozygosity at the COMT locus and OCD (homozygosity analysis: chi(2) = 5.66, P = 0.017; genotypic analysis: chi(2) = 5.78, P = 0.056). Although these findings do not replicate the previous reports, they do provide limited support to demonstrate a trend for homozygosity at the COMT locus in the OCD patients and, in turn, further implicate a potential role for COMT in the genetic etiology of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:721-724, 2000.

Alleles↗
PubMed2002

Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands.

The goal of this study was to identify chromosomal regions likely to contain susceptibility alleles for early-onset obsessive-compulsive disorder (OCD). A genome scan was done in 56 individuals from seven families ascertained through pediatric OCD probands; 27 of the 56 subjects had a lifetime diagnosis of definite OCD. Denser mapping of regions on chromosomes 2, 9, and 16 was subsequently done with those subjects and ten additional subjects from the largest family in the study. Direct interviews were completed with 65 of the 66 genotyped individuals. Relatives were interviewed blind to proband status. Of the 65 interviewed individuals, 32 had a lifetime diagnosis of definite OCD. Three of the seven probands had a history of Tourette disorder. Two of the 25 relatives with OCD had a tic history, whereas none of the 33 relatives without OCD had tics. The genome scan consisted of 349 microsatellite markers with an average between-marker distance of 11.3 centiMorgan (cM). Fine mapping was done with 24 additional markers at an average spacing of 1.6 cM. Parametric and nonparametric linkage analyses were conducted using GENEHUNTER(+). The maximum multipoint LOD score with a dominant model was 2.25 on 9p. However, with fine mapping and additional subjects, that LOD score decreased to 1.97. The maximum multipoint nonparametric LOD* score was 1.73 on 19q. The maximum multipoint LOD score with a recessive model was 1.40 on 6p. The results provide suggestive evidence for linkage on 9p and identify regions requiring further study with much larger samples.

Adolescent↗
PubMed2002

Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism.

The determination of a genetic basis for obsessive-compulsive disorder (OCD) depends on how phenotypic boundaries are defined. Although a hypothesis for serotonin dysfunction in OCD has been advanced, no genes specifically responsible for serotonin regulation have as yet been definitively related to the etiology of OCD. The phenotypic variability of OCD could be at the basis of the failure of molecular biology investigations to find any genes involved in the liability to the disorder. Obsessive and compulsive contents can aggregate in OCD patients differently; multifactorial description may therefore be able to account for OCD phenotypic variance. Using principal component analysis, we derived five factors from 13 main contents of the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and considered them as quantitative phenotypes to evaluate their possible association with an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR). A trend toward positive association between the fifth factor, including counting and repeating rituals, and 5-HTTLPR was found. However, only considering the subgroup of patients with tic codiagnosis, we found a significantly higher score for the fifth factor for patients with L/L genotype with respect to L/S and S/S genotypes.

Adolescent↗
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↗
PubMed2006

Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism.

Symptoms defining obsessive-compulsive disorder (OCD) are diverse. Factor analyses of OCD symptoms have been used to evaluate obsessive-compulsive phenotypes that are thought to be more homogenous than the macro phenotype. There is evidence that three factors (symmetry/ordering, obsessions/checking, and hoarding) are familial and preliminary evidence that repetitive rituals are associated with a functional polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR). The goal of this study was to examine relationships between OCD symptom dimensions and 5-HTTLPR. We genotyped 153 subjects who met DSM-IV criteria for OCD. We used the Yale-Brown obsessive-compulsive scale symptom checklist (YBOCS-SC) to assess OCD symptoms. Using principle components analysis, we derived four factors from the 13 symptom categories of the YBOCS-SC in this patient sample, which replicated previous factor analyses of this scale. The frequencies of the S allele and the SS genotype were associated with the second factor including obsessions regarding symmetry and compulsions involving repeating, counting, and ordering/arranging. This study may contribute to understanding of molecular genetic features underlying the appearance of symptom clusters in OCD.

Adult↗
PubMed2004

Role of magical thinking in obsessive-compulsive symptoms in an undergraduate sample.

Thought action fusion (TAF) is an important presenting feature of many individuals with obsessive-compulsive disorder (OCD). "Magical thinking" is a similar construct (developed within the literature on schizotypy) that may provide a more accurate depiction of difficulties encountered by individuals with OCD. This study seeks to examine relationships between components of magical thinking, TAF, and superstitiousness; establish the extent to which these constructs are independently related to OCD proneness; and establish the extent to which these biased reasoning styles are related to each of the major OCD symptom clusters (e.g., washing, checking). The Padua Inventory (PI), the Maudsley Obsessional-Compulsive Inventory (MOCI), the Magical Ideation Scale (MI), the Lucky Behaviours (Lbeh) and Lucky Beliefs (Lbel) Scales, and the Thought Action Fusion-Revised scale (TAF-R) were given to a cohort of 86 undergraduate students. Of all the measures, the MI scale was found to be the most strongly related to obsessive-compulsive symptoms. Large and significant relationships between MI scores and the two measures of OCD (i.e., MOCI and PI) were obtained even when alternative mediators (i.e., Lbeh, Lbel, TAF-R) were held constant. No other variable remained significantly related to the MOCI or PI when magical ideation scores were held constant. The findings suggest that a general magical thinking tendency may underpin previous observed links between superstitiousness, thought action fusion, and OCD severity.

Adult↗
PubMed2005

Influence of age of onset on clinical features in obsessive-compulsive disorder.

We compared early-onset and late-onset obsessive-compulsive disorder (OCD) patients in terms of demographic and clinical features. One hundred sixteen outpatients whose primary diagnosis was OCD according to DSM-IV diagnostic criteria were recruited. Early-onset (n=50) and late-onset (n=66) OCD groups were compared with respect to demographic variables and scores obtained on various scales. A male gender predominance was found in early-onset OCD group. Symmetry/exactness obsessions, religious obsessions, hoarding/saving obsessions, and hoarding/collecting compulsions also were significantly more frequent in the early-onset group than in the late-onset group. The results may suggest a phenotypic difference between the two groups. Further studies are needed to investigate the differences between early-onset and late-onset OCD groups to examine the hypothesis that early-onset OCD is a distinct subtype of the disorder.

Adult↗
PubMed2005

The expression of anger and its relationship to symptoms and cognitions in obsessive-compulsive disorder.

We compared the association between obsessive-compulsive disorder (OCD) and the expression of anger in a sample of 71 patients and 71 college students. Some authors [Rubenstein et al., J Anxiety Disord 1995;9:1-9] have proposed that anger and hostility underlie the symptoms of OCD; however, there has been little empirical study of this relationship. One recent study [Whiteside and Abramowitz, Cog Therapy Res 2004;28:259-268] with college undergraduates found that the association between OCD symptoms and anger was attributable to depressive symptoms. In the present study, we compared the expression of anger in a sample of patients diagnosed with OCD and nonclinical volunteers. Consistent with the previous study, we found increased levels of anger in patients with OCD as compared to control participants; however, these differences could be attributed to between-group differences in general distress. These results were discussed within the framework of the cognitive theory of OCD.

Adult↗
PubMed2006

Topiramate augmentation in treatment-resistant obsessive-compulsive disorder: a retrospective, open-label case series.

Serotonin reuptake inhibitors (SRIs) are considered first-line treatments for obsessive-compulsive disorder (OCD). Many patients achieve some response but remain symptomatic despite an adequate SRI trial. Recent neuroimaging data found abnormally high glutamatergic concentrations in children with OCD. Following selective serotonin reuptake inhibitor (SSRI) treatment, a decrease in OCD symptom severity was associated with a decrease in caudate glutamatergic concentrations. We initiated an investigation of adjunctive topiramate (an anticonvulsant agent with glutamatergic properties) in the treatment of patients with OCD who were partially or nonresponsive to SRI treatment. Sixteen consecutive outpatients with OCD (mean age = 41.1 years; range = 21-58 years), who were partial or nonresponders to SRI monotherapy or SRI combination therapy (antipsychotic, other antidepressant, or benzodiazepines), and had topiramate added over a minimum of 14 weeks, were reviewed. Baseline and endpoint Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) were evaluated retrospectively. Eleven of 16 patients were responders (68.8%) with a CGI-I score of much improved or very much improved. The mean dose of topiramate was 253.1 +/- 93.9 mg/day. The mean time to response was 9.2 +/- 4.5 weeks. CGI-S scores decreased significantly from initiation of topiramate until 26 weeks, from 6.1 +/- 0.9 to 4.5 +/- 1.3 (P < .001). This case series suggests some preliminary evidence that the addition of topiramate may be useful in treatment-resistant OCD.

Adult↗
PubMed2007

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder.

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.

Adolescent↗
PubMed2003

Obsessions and compulsions in anorexia nervosa subtypes.

OBJECTIVE: Obsession and compulsions in anorexia nervosa (AN) patients are often confused with the preoccupations and rituals that are characteristic of obsessive-compulsive disorder (OCD). We examined the type and frequency of characteristic OCD obsessions and compulsions in a large sample of AN patients. METHOD: In personal interviews with 324 AN patients, we assessed lifetime histories of eating disorder symptomatology and obsessive-compulsive behaviors with valid semistructured interviews. Checklist category sums on the Yale-Brown Obsessive Compulsive Scale were compared between AN and OCD subjects using generalized estimating equations. RESULTS: Lifetime obsessions and compulsions occurred in 68% of the AN restricting type and in 79.1% of the AN binge/purge type. The AN subgroups did not differ from OCD controls in frequency of obsessions in the symmetry and somatic categories or in the compulsion categories of ordering and hoarding. In all other categories, the AN subgroups had a significantly lower frequency compared with the OCD controls. DISCUSSION: Some common phenotype characteristics shared by most AN and OCD patients suggest these disorders may share common brain behavioral pathways. However, the lack of complete overlap indicates they most likely have different loci of pathology within those pathways.

Adult↗
PubMed2004

Challenges in treating obsessive-compulsive disorder: introduction.

This issue of In Session is devoted to challenges in the treatment of obsessive-compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises. Articles focus on the treatment of OCD with comorbid depression, compulsive hoarding, incompleteness, and repugnant obsessions, and on treatment of children who have OCD. The final article describes pharmacotherapy for OCD. All articles feature case vignettes and provide practitioners with clinical recommendations.

Adult↗
PubMed1999

The tryptophan depletion test. Impact on sleep in healthy subjects and patients with obsessive-compulsive disorder.

UNLABELLED: The tryptophan depletion test is a research tool to study the functional consequences of decreasing the brain serotonin metabolism. Since serotonin is involved in sleep regulation and assumed to be of high importance in the etiology of psychiatric disorders, the acute polysomnographic effects of tryptophan depletion were studied in healthy subjects and patients with obsessive compulsive disorder (OCD). According to the reciprocal interaction model of non-REM and REM-sleep regulation we expected that tryptophan depletion in healthy controls should provoke alterations of sleep similar to depression, whereas we assumed that these effects would be more pronounced in patients with OCD. METHODS: 12 healthy subjects with a mean age of 34 years and 12 patients suffering from OCD with a mean age of 30 years had 4 polysomnographic investigations. After 1 adaption and 1 baseline night subjects received a low protein diet on day 3 and 4 until midday. On day 4 at 18.00 h subjects ingested an aminoacid mixture devoid of tryptophan. This procedure resulted in a decrease of 85% in healthy subjects and 80% in OCD patients at 22.00 h. RESULTS: The tryptophan depletion led to more pronounced disturbances of sleep continuity in OCD patients than in healthy subjects in terms of an increase of wake time and a decrease of total sleep time. In both groups a decrease of sleep stage 2 could be observed. Healthy subjects showed significant alterations of phasic REM parameters as REM density and total number of rapid eye movements, what was not the case for OCD patients. CONCLUSIONS: Our results indicate the important role of the serotonergic system for sleep maintainance and the phasic aspects of REM sleep. Furthermore our data demonstrate that the tryptophan depletion test is a useful tool to evaluate the hypothesis of a serotonergic involvement in sleep regulation and the etiology of psychiatric disorders.

Adult↗
PubMed1996

Lipophilic 1-beta-D-arabinofuranosyl cytosine derivatives in liposomal formulations for oral and parenteral antileukemic therapy in the murine L1210 leukemia model.

The N4-alkylcytosine arabinoside derivative N4-octadecyl-AraC (AraC-Ocd, NOAC) and the (1-octadecylglycero-3-phospho)-AraC (Ocd-GroP-AraC, OPA) conjugate are new lipophilic derivatives of the cytostatic drug 1-beta-D-arabinofuranosylcytosine (AraC) that produce high antileukemic effects in the L1210 murine leukemia model when administered orally or parenterally as liposomal formulations. Between 83% and 100% of the treated animals were cured after five consecutive daily oral drug applications with a total dose of 1 mmol/kg AraC-Ocd or Ocd-GroP-AraC. Corresponding results were obtained after parenteral therapy on days 2 and 6 after tumor inoculation with five- to ten-fold lower concentrations of these two compounds. A comparable cytotoxic activity was found with the orally active AraC-5'-(n-stearyl phosphate). However, because of its strong hemolytic toxicity this derivative cannot be used for parenteral therapy. Another AraC conjugate, which was modified with two long-chain hydrocarbons, the (1-octadecylglycero-3-phospho)-N4-hexadecyl-AraC was, probably because of poor oral bioavailability, only active when applied parenterally. The new lipophilic AraC derivatives AraC-Ocd and Ocd-GroP-AraC are compounds with a high potential for the oral treatment of leukemias and possibly also of solid tumors.

Administration, Oral↗