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PubMed2005

A family study of obsessive-compulsive disorder with pediatric probands.

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. We examined the lifetime history of obsessions, compulsions, and OCD in the first- and second-degree relatives of 35 pediatric probands with OCD and 17 controls with no psychiatric diagnosis. All available first-degree relatives were directly interviewed blind to proband status with two semi-structured interviews. Parents were also interviewed to systematically assess the family psychiatric history of first- and second-degree relatives. Best-estimate lifetime diagnoses were made using all available sources of information. Data were analyzed with logistic regression by the generalized estimating equation method and with robust Cox regression models. The lifetime prevalence of definite OCD was significantly higher in case than control first-degree relatives (22.5% vs. 2.6%, P < 0.05). Compared to controls, case first-degree relatives also had significantly higher lifetime rates of obsessions and compulsions (both P < 0.05). There was no significant difference between case and control second-degree relatives in lifetime rates of OCD. First-degree relatives of case probands with ordering compulsions had a significantly higher lifetime rate of definite and subthreshold OCD than relatives of case probands without ordering compulsions (45.4% vs. 18.8%, P < 0.05). The lifetime prevalence of definite OCD was significantly higher in case first-degree relatives with a history of tics than in case first-degree relatives without a tic history (57.1% vs. 20.9%, P < 0.01). The results provide further evidence that early-onset OCD is highly familial and suggest that two clinical variables are associated with its familial aggregation.

Adolescent↗

PubMed2005

Obsessionality, obsessive-compulsive disorder, and temporal lobe epilepsy.

We evaluated the prevalence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE) and we investigated the hypothesis that obsessionality may represent a trait in TLE. Eighty-two consecutive patients with epilepsy, 62 with TLE and 20 with idiopathic generalized epilepsy (IGE), and 82 matched healthy controls were evaluated using the SCID-IP, Y-BOCS, MMPI-2 (specifically the Psychasthenia and Obsessiveness scales), BDI, and STAI Y1 and Y2. Nine of the TLE patients, none of the IGE patients, and one of the controls had a diagnosis of OCD. Psychasthenia and Obsessiveness scores were significantly higher in the TLE than in the IGE and control groups. Patients with TLE and OCD differed significantly with respect to history of depression when compared with patients with TLE without OCD, whereas there were no differences in age at onset and duration of epilepsy, seizure pattern and frequency, MRI features, laterality of the EEG focus, antiepileptic drug therapy and combinations, and BDI scores.

Adolescent↗

PubMed1997

What do patients do with their obsessive thoughts?

Current models of Obsessive-Compulsive Disorder (OCD) accord a key role to neutralization in the maintenance of obsessional thoughts. Although overt compulsions are well known and have frequently been described in the literature, their cognitive equivalents have not been described to any great extent. This study systemically described the repertoire of strategies used by 29 OCD patients with dominant obsessive thoughts. Extensive repertoires were reported, characterized by low to moderate mean efficacy in removing the thoughts. The majority of strategies were not cognitive rituals nor neutralization in the narrow sense of 'attempts at putting right', even though they were effortful, intentional, and deployed in a strategic way. The results are discussed in terms of the need for a broad definition of neutralization that includes all strategies including coping strategies. Clinical implications are discussed and comprehensive response prevention is recommended for the treatment of obsessive thoughts.

Adaptation, Psychological↗

PubMed1999

Symptom structure in obsessive-compulsive disorder: a confirmatory factor-analytic study.

Although obsessive-compulsive disorder (OCD) has long been a unitary diagnosis, there is much recent interest in its potential heterogeneity, as manifested by symptom subgroups. This study evaluated existing models of symptom structure in a sample of 203 individuals with OCD. Using confirmatory factor analysis, we examined the ability of each model to account for two levels of data: a priori symptom groupings (second-order) and individual symptoms, identified by the Yale-Brown Obsessive Compulsive Scale symptom checklist. Four models were examined: a single-factor, a two-factor (i.e., obsessions and compulsions), and two multidimensional models, comprising three and four factors. Adequate fit was found solely for the four-factor model--specifying obsessions/checking, symmetry/ordering, contamination/cleaning, and hoarding--but only at the second-order level; it did not account for relationships among discrete symptoms. Parameter estimates showed within-factor heterogeneity, as well as overlap between factors, most notably the two representing checking and contamination-related symptoms. The implications of these findings are discussed. Results provide evidence for the multidimensionality of OCD symptoms, but suggest that a comprehensive model has yet to be identified. They also point to the inadequacy of groupings based solely upon overt behavioural similarities (e.g., 'checking'). Recommendations are made for future research.

Adult↗

PubMed1987

Inter-rater reliability of a classification of obsessions and compulsions.

Weighted kappa and random error coefficient was used to determine inter-rater reliability of a proposed classification of obsessions and compulsions. A high reliability was found between 3 raters for obsessive and compulsive form and content. This classification allows for greater precision in classifying obsessive-compulsive phenomena in research.

Compulsive Behavior↗

PubMed2005

Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea.

The authors investigated obsessive-compulsive behavior, obsessive-compulsive disorder (OCD), and attention deficit and hyperactivity disorder (ADHD) in 50 healthy subjects, 50 patients with rheumatic fever without chorea, and 56 patients with Sydenham chorea. Obsessive-compulsive behavior, OCD, and ADHD were more frequent in the Sydenham chorea group (19%, 23.2%, 30.4%) than in the healthy subjects (11%, 4%, 8%) and in the rheumatic fever without chorea group (14%, 6%, 8%). ADHD was more common in persistent Sydenham chorea.

Adolescent↗

PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans↗

PubMed2022

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans↗

PubMed1977

Treatment of obsessive-compulsive neurosis with clomipramine (Anafranil).

An uncontrolled clinical study was carried out to evaluate the therapeutic efficacy of clomipramine (Anafranil, Geigy Pharmacueticals) in a group of twenty obsessive-compulsive neurotic patients. Clomipramine proved to be extremely useful in alleviating obsessive-compulsive neurosis as well as phobia. This finding was not secondary to the improvement in anxiety or depression which occurred, as the degree of improvement in obsessive symptoms far exceeded the improvement in the other symptoms.

Adult↗

PubMed2004

Treatment outcome of schizophrenia co-morbid with obsessive-compulsive disorder.

OBJECTIVE: To evaluate the pharmacological treatment outcome of schizophrenia, co-morbid with obsessive-compulsive disorder by comparing the effects of typical neuroleptic, atypical neuroleptic and a combination of typical with anti-obsessional drugs on positive and negative symptoms of schizophrenia and obsessional symptoms. DESIGN: A quasi-experimental study. PLACE AND DURATION OF STUDY: The study was conducted at the Department of Psychiatry, Postgraduate Medical Institute and Services hospital, Lahore from September 2002 to July 2003. SUBJECTS AND METHODS: The sample consisted of 39 patients suffering from schizophrenia co-morbid with obsessive-compulsive disorder. They were divided in three groups according to the pharmacological treatment given by the treating psychiatrists. Sample was assessed at the start of treatment and twelve weeks later. RESULTS: Patients receiving typical neuroleptics and anti-obsessional drugs showed better outcome (p <.05) both in psychotic (pre-intervention mean scores of positive scale of PANSS 26.90 as compared to postinterventional mean scores 19.00) and obsessional symptoms (pre-intervention mean scores on Padua Inventory 165.00 compared to 84.00 postinterventional mean scores) than those receiving typical and atypical neuroleptics alone. CONCLUSION: Treatment outcome of schizophrenia co-morbid with obsessive-compulsive disorder shows better results if anti-obsessional drugs are added to the neuroleptics.

Adult↗

PubMed2003

Demographic and clinical characteristics of adolescents in Hawaii with obsessive-compulsive disorder.

BACKGROUND: A high prevalence rate of obsessive-compulsive disorder (OCD) among Hawaiian adolescents, particularly Native Hawaiians, has been reported. Because Native Hawaiian and other Polynesian youth are at an increased risk for rheumatic fever, caused by an autoimmune response to group A beta-hemolytic streptococci, we hypothesized that the genetic and environmental risk factors for streptococcal infections and their autoimmune sequelae potentially may be associated with the presence of OCD and may partially explain this high OCD prevalence. OBJECTIVE: To describe, among the adolescents in Hawaii diagnosed as having OCD through a previous study, OCD prevalence by ethnicity, household crowding and other measures of socioeconomic status, various measures of physical health and health-seeking behavior, and comorbid psychopathologic features. DESIGN: Six hundred nineteen adolescents from 5 high schools in the state of Hawaii were interviewed from April 15, 1993, to May 7, 1996. Interview instruments included the Diagnostic Interview Schedule for Children and other measurements of psychopathology. Obsessive-compulsive disorder diagnoses, based on current and past 6-month symptoms elicited via structured interview of the adolescents, were reported. RESULTS: Relative to other ethnicities, Native Hawaiians had a 2-fold higher risk (odds ratio = 2.03) for OCD. Degree of Polynesian ancestry correlated positively with OCD prevalence. Obsessive-compulsive disorder prevalence also correlated positively with crowding in the household; measures of physical illness; and measures of depression, anxiety, aggression, and illicit substance use. CONCLUSIONS: The characteristics of OCD in this sample suggest the need to consider the possibility of a streptococcal origin and the need for further studies to clarify the genetic and environmental risk factors for OCD in Hawaiian and other Polynesian youth.

Adolescent↗

PubMed1990

Standardized assessment of personality disorders in obsessive-compulsive disorder.

We assessed 96 patients with obsessive-compulsive disorder for DSM-III personality disorder diagnoses with a standardized interview instrument (Structured Interview for the DSM-III Personality Disorders). Fifty patients (52%) met criteria for at least one personality disorder, with mixed, dependent, and histrionic personality disorders most frequently diagnosed. Compulsive personality disorder was diagnosed in only 6 patients (6%), 5 of whom had had onset of obsessive-compulsive symptoms before the age of 10 years, indicating that DSM-III compulsive personality disorder is not invariably a premorbid condition for the development of obsessive-compulsive disorder. Schizotypal personality disorder, at 5%, was found to be less common than in past samples, reflecting differences in either assessment methods or sampling.

Adolescent↗

PubMed1990

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine.

In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive-compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus.

Adult↗

PubMed1991

A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder.

Twenty-six children and adolescents with severe primary obsessive-compulsive disorder receiving long-term clomipramine hydrochloride maintenance treatment (mean +/- SD, 17.1 +/- 8.3 months; range, 4 to 32 months) entered an 8-month double-blind desipramine hydrochloride substitution study to assess the necessity of continued drug treatment. All patients received clomipramine for the first 3 months, then half continued with clomipramine therapy (nonsubstituted group) and half had desipramine blindly substituted for the next 2 months; all subjects again received clomipramine for the last 3 study months. Eight (89%) of nine of the substituted and only two (18%) of 11 of the nonsubstituted group subjects relapsed during the 2-month comparison period. Long-term clomipramine treatment seems necessary for this population of children and adolescents with obsessive-compulsive disorder. However, even patients receiving maintenance clomipramine treatment throughout the entire study had continued obsessive-compulsive symptoms, which varied in severity over time.

Adolescent↗

PubMed1992

Serotonergic function in obsessive-compulsive disorder. Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers.

To evaluate serotonergic (5-hydroxytryptamine) function in obsessive-compulsive disorder, behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) and fenfluramine hydrochloride (60 mg orally) were examined in 20 patients and 10 healthy controls under double-blind, placebo-controlled conditions. Following m-CPP, but not fenfluramine or placebo, 55% (11/20) of the patients with obsessive-compulsive disorder experienced a transient exacerbation of obsessive-compulsive disorder. Prolactin response was blunted in patients following m-CPP but not following fenfluramine. Patients with greater behavioral response to m-CPP had smaller prolactin responses. Cortisol response to m-CPP and fenfluramine did not significantly differ between the groups. Behavioral and neuroendocrine responses appeared divergent. This does not suggest simply upregulation or downregulation of 5-hydroxytryptamine receptors, but rather complex mechanisms involving multiple neurotransmitter and neuromodulator systems.

Administration, Oral↗

PubMed1992

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder.

We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms.

Adult↗

PubMed1992

Effect of axis II diagnoses on treatment outcome with clomipramine in 55 patients with obsessive-compulsive disorder.

We used the Structured Interview for DSM-III Personality Disorders to diagnose DSM-III personality disorders systematically in 55 patients with obsessive-compulsive disorder in the active-treatment cell of a controlled trial of clomipramine hydrochloride. Patients with a cluster A personality disorder had significantly higher obsessive-compulsive disorder severity scores at baseline, and the number of personality disorders was strongly related to baseline severity of obsessive-compulsive disorder symptoms. At the conclusion of the 12-week study, we found no significant difference in treatment outcome with clomipramine between those patients with at least one personality disorder and those with no personality disorders. However, the presence of schizotypal, borderline, and avoidant personality disorders, along with total number of personality disorders, did predict poorer treatment outcome. These variables were strongly related to having at least one cluster A personality disorder diagnosis, which was also a strong predictor of poorer outcome. Implications of these findings are discussed.

Adult↗

PubMed1994

Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics.

BACKGROUND: To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment. METHODS: Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome. RESULTS: Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response. CONCLUSIONS: The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction.

Adolescent↗