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PubMed1994

Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors.

METHODS: The effects of short-term tryptophan depletion were examined in 15 patients with DSM-III-R obsessive-compulsive disorder who had demonstrated symptom reduction following treatment with serotonin reuptake inhibitors. Patients received a 24-hour, low-tryptophan (160-mg/d) diet followed the next morning by a drink of 15 amino acids. A double-blind, placebo-controlled cross-over design was used. RESULTS: The diet and the amino acid drink reduced free plasma tryptophan levels by a mean of 84% 5 hours later. Short-term tryptophan depletion did not significantly change mean ratings of obsessions and compulsions. In contrast, mean depression ratings were significantly increased with tryptophan depletion compared with the control (tryptophan-supplemented) testing. CONCLUSION: Maintenance of serotonin reuptake inhibitor-induced improvement of obsessive and compulsive symptoms, unlike remission of depressive symptoms, may not depend on ongoing short-term availability of serotonin.

Adult↗
PubMed1994

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.

Adolescent↗
PubMed1995

Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis.

BACKGROUND: Questions have been raised regarding the relative efficacy and tolerability of the different serotonin transport inhibitors in the treatment of obsessive-compulsive disorder. We compared the results from four large multicenter placebo-controlled trials of the serotonin transport inhibitors clomipramine hydrochloride (N = 520), fluoxetine hydrochloride (N = 355), fluvoxamine maleate (N = 320), and sertraline hydrochloride (N = 325) for the treatment of obsessive-compulsive disorder. METHODS: Effect size was calculated by subtracting the end-point drug treatment mean change from the end-point placebo mean change and dividing by the end-point pooled change standard deviation. A test for overall differences between effect sizes was conducted, followed by all possible pairwise comparisons. The Yale-Brown Obsessive Compulsive Scale was the primary outcome measure for all four studies. RESULTS: All four agents were significantly more effective than placebo, with clomipramine significantly more effective than the other three treatments, which did not differ in effect size. A significantly greater percentage of patients treated with clomipramine were rated much or very much improved than were patients treated with fluoxetine, fluvoxamine, or sertraline. CONCLUSION: While the results of this meta-analysis support the superiority of clomipramine, head-to-head, double-blind comparisons of these compounds would be the best test of comparative efficacy and tolerability.

1-Naphthylamine↗
PubMed1998

Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study.

BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine. METHODS: Fifty-four patients with oral clomipramine-refractory OCD were randomized to receive 14 infusions of either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 patients. Response was based on a Clinical Global Impressions rating of at least "much improved." RESULTS: Six (21%) of 29 patients randomized to receive intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were responders after 14 infusions (df = 1, P<.02). Dimensional ratings after infusion 14 revealed significant (P = .007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week later, all dimensional measures of OCD showed significant improvement. At 1 week post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and treated subsequently with oral clomipramine were responders, whereas 0 of 18 patients initially randomized to receive i.v. placebo and treated subsequently with several days of open-label i.v. clomipramine responded (df = 1, P<.002). Of the 31 patients assessed 1 month after i.v. infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences. CONCLUSIONS: Intravenous clomipramine is more effective than i.v. placebo for patients with OCD with a history of inadequate response or intolerance to oral clomipramine. Further study of this promising treatment for refractory OCD is needed.

Administration, Oral↗
PubMed2004

Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder.

CONTEXT: Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous functional neuroimaging studies grouped together patients with mixed symptoms, thus potentially reducing the power and obscuring the findings of such studies. OBJECTIVE: To investigate the neural correlates of washing, checking, and hoarding symptom dimensions in OCD. DESIGN: Symptom provocation paradigm, functional magnetic resonance imaging, block design, and nonparametric brain mapping analyses. SETTING: University hospital. PARTICIPANTS: Sixteen patients with OCD (11 inpatients, 5 outpatients) with mixed symptoms and 17 healthy volunteers of both sexes. Intervention All subjects participated in 4 functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of emotional (washing-related, checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral pictures, and imagining scenarios related to the content of each picture type.Main Outcome Measure Blood oxygenation level-dependent response. RESULTS: Both patients and control subjects experienced increased subjective anxiety during symptom provocation (patients significantly more so) and activated neural regions previously linked to OCD. Analyses of covariance, controlling for depression, showed a distinct pattern of activation associated with each symptom dimension. Patients demonstrated significantly greater activation than controls in bilateral ventromedial prefrontal regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus, and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated). These results were further supported by correlation analyses within patients, which showed highly specific positive associations between subjective anxiety, questionnaire scores, and neural response in each experiment. There were no consistently significant differences between patients with (n = 9) and without (n = 7) comorbid diagnoses. CONCLUSIONS: The findings suggest that different obsessive-compulsive symptom dimensions are mediated by relatively distinct components of frontostriatothalamic circuits implicated in cognitive and emotion processing. Obsessive-compulsive disorder may be best conceptualized as a spectrum of multiple, potentially overlapping syndromes rather than a unitary nosologic entity.

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↗
PubMed1998

The relationship between body dysmorphic disorder and depression, self-esteem, somatization, and obsessive-compulsive disorder.

The present study investigated the relationship of depression, self-esteem, somatization, and obsessive-compulsive disorder to the incidence of body dysmorphic disorder (BDD). Female (n=83) and male (n=25) undergraduates completed measures of body esteem, self-esteem, obsessive-compulsive behavior, and somatization. Subjects were also screened for eating disorders utilizing the DSM-IV criteria for such in an effort to control for anorexia and bulimia. Upon excluding those subjects who met the criteria for eating disorders, the final sample included 78 females and 24 males. The results indicated that lower body esteem scores were linked with lower levels of self-esteem but with higher levels of obsessive-compulsive tendencies, depressive tendencies, and somatization tendencies. The findings are discussed with regard to the need for more accurate measures of body dysmorphic disorder, as well as etiology and future treatment implications.

Adolescent↗
PubMed2004

Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.

The study of neurogenetic microdeletion syndromes provides an insight into the developmental psychopathology of psychiatric disorders. The aim of the study was to evaluate the prevalence of psychiatric disorders, especially obsessive-compulsive disorder (OCD), in patients with velocardiofacial syndrome (VCFS), a 22q11 microdeletion syndrome. Forty-three subjects with VCFS of mean age 18.3 +/- 10.6 years were comprehensively assessed using semi-structured psychiatric interview and the Yale-Brown obsessive compulsive scale (Y-BOCS). Best estimate diagnoses were made on the basis of information gathered from subjects, parents, teachers, and social workers. Fourteen VCFS subjects (32.6%) met the DSM-IV criteria for OCD. OCD had an early age of onset and generally responded to fluoxetine treatment. It was not related to mental retardation. The most common obsessive-compulsive symptoms were contamination, aggression, somatic worries, hoarding, repetitive questions, and cleaning. Sixteen of the 43 patients (37.2%) had attention-deficit/hyperactivity disorder (ADHD), and 7 (16.2%) had psychotic disorder. The results of our study suggest that there is a strong association between VCFS and early-onset OCD. This finding may be significant in the understanding of the underlying genetic basis of OCD.

Adolescent↗
PubMed2005

Familial aggregation of schizophrenia-spectrum disorders and obsessive-compulsive associated disorders in schizophrenia probands with and without OCD.

A substantial proportion of schizophrenia patients also has obsessive-compulsive disorder (OCD). To further validate the clinical validity of a schizo-obsessive diagnostic entity, we assessed morbid risks for schizophrenia-spectrum disorders and OC-associated disorders in first-degree relatives of schizophrenia probands with and without OCD. Two groups of schizophrenia probands [with OCD (n = 57) and without OCD (n = 60)] and community-based controls (n = 50) were recruited. One hundred eighty two first-degree relatives of probands with OCD-schizophrenia, 210 relatives of non-OCD schizophrenia probands, and 165 relatives of community subjects were interviewed directly [59.3% (108/182), 51.9% (109/210), and 54.5% (90/165), respectively], using the Structured Clinical Interview for Axis-I DSM-IV Disorders and Axis II DSM-III-R Personality Disorders and the remaining relatives were interviewed indirectly, using the Family History Research Diagnostic Criteria. Relatives of OCD-schizophrenia probands had significantly higher morbid risks for OCD-schizophrenia (2.2% vs. 0%; P = 0.033) and OCPD (7.14% vs. 1.90%; P = 0.014), and a trend towards higher morbid risk for OCD (4.41% vs. 1.43%; P = 0.08) compared to relatives of non-OCD schizophrenia probands. When morbid risks for OCD, OCPD, and OCD-schizophrenia were pooled together, the significant between-group difference became robust (13.74% vs. 3.33%; P = 0.0002). In contrast, relatives of the two schizophrenia groups did not differ significantly in morbid risks for schizophrenia-spectrum disorders, mood disorders, or substance abuse disorders. A differential aggregation of OC-associated disorders in relatives of OCD-schizophrenia versus non-OCD schizophrenia probands, provides further support for the validity of a putative OCD-schizophrenia ("schizo-obsessive") diagnostic entity.

Adult↗
PubMed2002

Childhood trauma in obsessive-compulsive disorder, trichotillomania, and controls.

There is relatively little data on the link between childhood trauma and obsessive-compulsive/putative obsessive-compulsive spectrum disorders. The revised Childhood Trauma Questionnaire (CTQ), which assesses physical, emotional, and sexual abuse as well as physical and emotional neglect, was administered to female patients with obsessive-compulsive disorder (OCD; n = 74; age: 36.1 plus minus 16.3), TTM (n = 36; age: 31.8 plus minus 12.3), and a group of normal controls (n = 31; age: 21.5 plus minus 1.0). The findings showed a significantly greater severity of childhood trauma in general, and emotional neglect specifically, in the patient groups compared to the controls. Although various factors may play a role in the etiology of both OCD and trichotillomania (TTM), this study is consistent with some evidence from previous studies suggesting that childhood trauma may play a role in the development of these disorders.

Adolescent↗
PubMed2003

Group behavioral therapy for adolescents with tic-related and non-tic-related obsessive-compulsive disorder.

Prior research supports the distinction between tic-related and non-tic-related obsessive-compulsive disorder (OCD) based on phenomenologic, etiologic, and neurobehavioral data. The present study examines whether response to psychosocial treatment differs in adolescents, depending on the presence of comorbid tics. Nineteen adolescents, 12-17 years of age, participated in 7-week, uncontrolled trial of group cognitive-behavioral treatment (CBT) for OCD. Eight of the patients had tic-related and eleven had non-tic-related OCD. The group CBT program included psycho-education, exposure and response prevention, cognitive strategies, and family involvement. Significant improvement was observed for all subjects on the Yale-Brown Obsessive Compulsive Scale ratings of obsessions, compulsions, and total OCD symptoms. Outcomes were similar for subjects with tic-related and non-tic-related OCD. These preliminary results suggest that the presence of comorbid tic disorders may not attenuate response to behavioral group treatment among adolescents.

Adolescent↗
PubMed2004

Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder.

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone.

Acute Disease↗
PubMed2006

Morphometric alterations of anterior superior temporal cortex in obsessive-compulsive disorder.

The superior temporal gyrus (STG) may be involved in the pathophysiology of obsessive-compulsive disorder (OCD). Moreover, the anterior STG has rich interconnections with the orbitofrontal cortex and the amygdala, and plays a role in visuospatial processing, which is impaired in patients with OCD. This study was designed to examine the morphological abnormalities of the anterior STG and their relationships with visuospatial function and clinical symptom in patients with OCD. We measured gray matter volumes of the anterior STG [rostral STG and planum polare (PP)] by three-dimensional (3D) magnetic resonance imaging in age- and sex-matched groups, which consisted of 22 patients with OCD and 22 normal volunteers. Visuospatial function and clinical symptom were assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Yale-Brown Obsessive Compulsive Scale, and the Maudsley Obsessive Compulsive Inventory. We found significant volume reductions in bilateral PPs, but there were no significant correlations between brain volumes and the ROCF copy score, immediate or delayed recall score, and clinical symptom in patients with OCD. These results suggest that volume reduction of the anterior STG, especially the PP, may be related to the pathophysiology of OCD, but further research may be needed to explore a relationship of the PP volume change with cognitive impairment observed in patients with OCD.

Adult↗
PubMed2007

Electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder.

In this study, we have attempted to determine the electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder (OCD). To evaluate response inhibition ability, we have used the Go/NoGo task and measured N2 and P3 event-related potential (ERP) components. Both the OCD and control groups exhibited greater and more frontally distributed N2 and P3 amplitudes in the NoGo condition compared to what we observed in the Go condition. However, the patients with OCD also manifested reduced NoGo-N2 and Go-N2 amplitudes at the frontocentral electrode sites compared to the controls. In addition, the NoGo-N2 amplitudes were more posteriorly distributed in patients with OCD than in controls. The NoGo-N2 amplitudes and latencies measured at the central sites were also negatively correlated with the obsession score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The OCD and control groups were comparable with regard to Go-P3 and NoGo-P3 amplitude and latencies. Our findings suggest dysfunctions in frontal regions mediating response inhibition in OCD, consistent with the involvement of response inhibition in the pathophysiology of this disorder. In addition, NoGo-N2 seems to result in more accurate response inhibition measurements in patients with OCD than does NoGo-P3.

Adult↗
PubMed2005

Anorexia nervosa and obsessive-compulsive disorder in a prepubertal patient with bone dysplasia: a case report.

OBJECTIVE: The current article describes the case of a 13-year-old girl with body dysplasia, anorexia nervosa, and obsessive-compulsive disorder (OCD). METHOD: She was given cognitive-behavioral therapy and pharmacologic treatment for the obsessive-compulsive symptomatology and exogenous growth hormone to increase her height. RESULTS: She experienced an adequate weight and height increase and remission of obsessive-compulsive symptomatology, and reestablished adequate social and academic functioning. CONCLUSION: After a follow-up of almost 2 years, she had had her menarche, continued her positive eating habits, and had not relapsed into OCD.

Adolescent↗
PubMed1996

Treatment of obsessive-compulsive disorder in children and adolescents. A review of the literature.

The literature on treatment of childhood and adolescent obsessive-compulsive disorder is reviewed. Most studies concerning treatment of obsessive-compulsive disorder has been based on experience from adult patients. Only a few controlled trials using medication with obsessive-compulsive children have been produced. No controlled study has as yet documented the effect of behavioural therapy alone. The most effective treatment seems to be a combination of behavioural therapy and medication with a serotonin reuptake inhibitor. In the treatment of children with OCD, it is important to consider the child's personality and comorbid disorders.

Adolescent↗
PubMed1993

The Zurich Study. XVIII. Obsessive-compulsive disorders and syndromes in the general population.

The cross-sectional and longitudinal association between obsessive-compulsive syndrome (OCS) and other psychiatric problems and the course over 11 years was examined in a Swiss cohort of young adults. As the prevalence of obsessive-compulsive disorders, defined according to the DSM-III was very low (n = 5), we applied a lower diagnostic threshold based on obsessive-compulsive symptoms and social impairment, to define an OCS. The weighted lifetime prevalence rate for OCS at age 30 years was 5.5%. The mean age of onset was 17.1 +/- 4.9 years for males, and 19.1 +/- 5.1 year for females. OCS was associated with all subtypes of depressive disorders as well as with social phobia and agoraphobia. Although the longitudinal analysis showed no stability at the diagnostical level, there was some stability on the symptom level. Perhaps subjects with OCS learned in time to cope and to live with their symptoms without suffering.

Adaptation, Psychological↗
PubMed1996

Pentagastrin has panic-inducing properties in obsessive compulsive disorder.

The effects of the CCKB-receptor agonist pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK-4), were studied in seven patients suffering from obsessive compulsive disorder (OCD) and seven healthy controls. All subjects were challenged with an IV dose of 0.6 micrograms/kg pentagastrin or placebo under double blind placebo controlled conditions, on two separate occasions, with a minimum interval of 1 week. Six (86%) out of seven OCD patients experienced a panic-like reaction after pentagastrin administration, against only two (29%) in the control group. These differences failed to reach statistical significance, probably due to the small sample size. No increases were observed in obsessions or compulsive behaviors as assessed with the Yale-Brown Obsessive Compulsive Challenge Scale, neither in the pentagastrin, nor in the placebo condition. These findings suggest that pentagastrin has panic-inducing properties in OCD patients, without affecting the core symptoms. The panic-inducing properties of pentagastrin are not specific for panic disorder patients, which might be indicative of a common neurobiological dysfunction in panic disorder and OCD at the level of CCK-B receptors.

Adult↗