Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin

OBJECTIVE: To compare, via a pilot study, the effectiveness of behavior therapy and of drug treatment in children and adolescents with obsessive-compulsive disorder. METHOD: Twenty-two children aged between 8 and 18 years were randomly assigned to behavior therapy (n = 12) or open clomipramine (n = 10) in a parallel design lasting 12 weeks. Behavior therapy included exposure and response prevention administered in weekly sessions. The mean dosage of clomipramine was 2.5 mg/kg (range = 1.4-3.3 mg/kg). The main outcome variables were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Leyton Obsessional Inventory-Child Version (LOI-CV). RESULTS: Significant improvement was obtained in both treatment conditions. Behavior therapy produced stronger therapeutic changes than clomipramine on the CY-BOCS (p < .05), whereas on the LOI-CV no significant differences between the results of the two treatments were found. Five of the nine initial nonresponders showed significant changes after extension of treatment for another 12 weeks. CONCLUSION: Behavior therapy is shown to be a good alternative for drug treatment and deserves further study in larger samples of children with obsessive-compulsive disorder.     

Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass

Although obsessive-compulsive disorder (OCD) is often considered a heterogeneous condition, there is no generally accepted subtype typology. Cluster analysis was used to identify definitive symptom-based groupings of 106 OCD patients. A stable cluster solution was achieved and five patient subgroups were identified based on their pattern of symptoms on the Yale-Brown (Y-BOCS) symptom checklist: harming, hoarding, contamination, certainty and obsessionals. The five subgroups were characterized by dominant symptom patterns and significant secondary concerns reflecting the symptom heterorgenaity often seen in the clinical presentation of obsessional patents. Between cluster differences on multiple symptom measures were evaluated and several meaningful differences were identified. Cluster analytic procedures may prove to be a useful tool for identifying a functional taxonomy of OCD subtypes.     

Cerebral structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric magnetic resonance imaging study

BACKGROUND: A previous pilot study of only posterior brain regions found lower white-matter volume in patients with obsessive-compulsive disorder than in normal control subjects. We used new cohorts of patients and matched normal control subjects to study whole-brain volume differences between these groups with magnetic resonance imaging-based morphometry. METHODS: Ten female patients with obsessive-compulsive disorder and 10 female control subjects, matched for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized and segmented by means of well-characterized semiautomated intensity contour mapping and differential intensity contour algorithms. Brain structures investigated included the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus pallidus, hippocampus amygdala, third and fourth ventricles, corpus callosum, operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions, including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum, with adjacent white matter were also measured. Volumes found different between groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth Complex Figure Test measures. RESULTS: Confirming results of our earlier pilot study and expanding the findings to the whole brain, patients with obsessive-compulsive disorder had significantly less total white matter but, in addition, significantly greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder and nonverbal immediate memory correlated with opercular volume. CONCLUSIONS: Replication of volumetric white-matter differences suggests a widely distributed structural brain abnormality in obsessive-compulsive disorder. Whereas determining the etiogenesis may require research at a microscopic level, understanding its functional significance can be further explored via functional neuroimaging and neuropsychological studies.     

A preliminary study of partial hospital management of severe obsessive-compulsive disorder

OBJECTIVE: The study examined the effectiveness of a partial hospital treatment program combining behavioral therapy, medication, and psychosocial intervention for severe and treatment-resistant obsessive-compulsive disorder. METHODS: A total of 58 patients with a primary diagnosis of obsessive-compulsive disorder who underwent treatment in a partial hospital program were assessed at baseline, at program discharge, and at six-, 12-, and 18-month follow-ups. Obsessive-compulsive symptoms, depression, anxiety symptoms, and global functioning were rated. RESULTS: The majority of patients (71 percent) met the criterion for a successful outcome, which was a 25 percent decrease in score on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Fifty-five percent finished the program with YBOCS scores of 16 or less, indicating only mild symptoms. Most of these patients sustained their improvement at six, 12, and 18 months after discharge, and many showed further improvement with continued outpatient management. CONCLUSIONS: The partial hospital treatment program for obsessive-compulsive disorder appears to be an effective intervention that should be implemented and investigated further.     

Screening for carbon monoxide in children

We present the use of risperidone as a potentiation strategy of the serotonergic antidepressants in four patients suffering from refractory obsessive-compulsive disorder. There were an important improvement in three patients. Adding risperidone to serotonergic antidepressants causes complex interactions between serotonergic, dopaminergic and noradrenergic systems, that could lay to the clinical improvement. These and other similar cases make necessary controlled studies. Adding risperidone to serotonergic antidepressants in patients suffering from refractory obsessive-compulsive disorder might be an effective strategy with low risk for secondary effects and without the presence of tics or psychotic symptoms.     

Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder?

OBJECTIVE: In obsessive-compulsive disorder, the relationship between blood levels of serotonin reuptake inhibitors and clinical outcome is unclear. In a multicenter trial, the authors examined the relationship between steady state plasma levels of fluoxetine and norfluoxetine (determined after 7 weeks of treatment), and their sum, and clinical outcome. METHOD: Ratings of symptom severity of obsessive-compulsive disorder (Yale-Brown Obsessive Compulsive Scale scores) were obtained at baseline and after 13 weeks for 200 adult outpatients with moderately severe obsessive-compulsive disorder treated with fluoxetine doses of 20 mg/day (N = 68), 40 mg/day (N = 64), and 60 mg/day (N = 68). RESULTS: Mean plasma levels of fluoxetine and norfluoxetine were statistically significantly higher with higher dose. Statistical analyses revealed no significant relationship for plasma level of either molecule or their sum in predicting endpoint percent change in obsessive-compulsive scores. Plasma levels of patients with a marked response (decrease of 50% or more in obsessive-compulsive score) did not differ significantly from those of nonresponders (less than a 25% decrease in obsessive-compulsive score). No hint was seen of a therapeutic window or of a relationship limited to one gender or within the lowest dose group (20 mg/day). However, since S-norfluoxetine is a much more potent serotonin reuptake inhibitor than R-norfluoxetine, the absence of chiral (stereospecific) assays in this study limits the results. CONCLUSIONS: Steady state plasma levels of fluoxetine and norfluoxetine are not related to clinical outcome in patients with obsessive-compulsive disorder. Individual patients can be told only that the optimum dose of fluoxetine for them will be the dose that produces the largest therapeutic effect with the smallest side effect burden. Future studies should examine the predictive utility of measures of serotonergic neuronal function and, if plasma levels of norfluoxetine are examined, the use of chiral assays.     

Obsessive-compulsive disorder in the community: an epidemiologic survey with clinical reappraisal

OBJECTIVE: To examine the prevalence of obsessive-compulsive symptoms and DSM-IV obsessive-compulsive disorder (OCD), the authors conducted a telephone survey of 2,261 adults in four regions of Canada. METHOD: Trained lay interviewers administered a modified version of the OCD section of the Comprehensive International Diagnostic Interview. A subsample of respondents with probable cases and probable subclinical cases of OCD was then blindly reinterviewed by research personnel experienced in the assessment of OCD, using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale, to confirm the diagnosis and gauge the severity of OCD. RESULTS: The weighted 1-month prevalence of OCD in the entire sample according to the lay interviews was 3.1%. Upon clinical reappraisal, the 1-month prevalence estimate of OCD dropped to 0.6%; an additional 0.6% had subclinical OCD. The mean Yale-Brown Obsessive Compulsive Scale score of the individuals with OCD was 19.0 (SD = 4.6, median = 21); for those with subclinical OCD, the mean score was 15.4 (SD = 2.4, median = 14). Common reasons for overdiagnosis of OCD by the lay interviewers were inappropriate labeling of worries or concerns as obsessions and overestimating the degree of interference or distress attributable to obsessive-compulsive symptoms. CONCLUSIONS: OCD, while hardly a rare condition, may be somewhat less prevalent than had been believed on the basis of previous surveys. Additional studies are needed to substantiate these findings and to delineate precisely the extent of disability and reduced quality of life attributable to OCD (and OCD variants) in the community.     

Infiltrative basal cell carcinoma occurring in sites of biopsy-proven nodular basal cell carcinoma

OBJECTIVE: The authors studied factors associated with short-term treatment response in 38 nondepressed subjects with DSM-III-R obsessive-compulsive disorder (OCD). METHOD: The subjects completed 12 weeks of treatment with paroxetine (N = 20), placebo (N = 8), or cognitive-behavioral therapy (N = 10). Clinician and self-rated measures were gathered at baseline, during treatment, and after treatment. RESULTS: Seventeen (45%) subjects had "much" or "very much" improvement and achieved at least a 40% decrease in their total Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Responders had lower obsessive-compulsive scores on the Symptom Checklist 90-Revised, had a lower checking score on the Maudsley Obsessive-Compulsive Inventory, were less likely to have had prior drug therapy, and in general suffered more obsessive-compulsive symptoms. They were significantly less likely to have hoarding obsessions and corresponding compulsions. The latter finding was confirmed using multiple regression analysis. CONCLUSION: Hoarding is an important symptom that predicts poor treatment response in patients with OCD.     

The role of the nurse practitioner in promoting sexuality in the institutionalized elderly

Some studies suggest a relationship between obsessive-compulsive disorder (OCD) and Gilles de la Tourette's syndrome. The pathophysiology of the latter may involve the dopamine system. We screened three important exons of the dopamine D2 receptor (DRD2) gene for mutations in a group of OCD patients with or without tics. No structural changes were found, suggesting no relationship between DRD2 and OCD. Moreover, the frequency of the polymorphism in exon 6 was different from that found in schizophrenics.     

Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder

Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive Scale (19 + or - 9 vs. 22 + or - 6). This suggests that these disorders have similar magnitude of impairment from obsessions and compulsions; however, OCD patients endorsed a wide variety of obsessions and compulsions, whereas anorexics tended to endorse symptoms that were related to symmetry and order.     

Antibodies against human putamen in children with Tourette syndrome

BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies, which develop in response to a preceding streptococcal infection, have been speculated to have a role in the development of Tourette syndrome (TS). METHODS: Serum antibodies against human caudate, putamen, and globus pallidus (interna and externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques and results were correlated with clinical characteristics and markers of streptococcal infection. SUBJECTS: A total of 41 children with TS (mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included. RESULTS: Compared with controls, TS subjects had a significant increase in the mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum antibodies against putamen, but not caudate or globus pallidus. Western blots on 20 control and 20 TS serum samples showed that specific antibodies to caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa; antigens were present in a synaptosomal fraction. TS subjects with a positive family history of tics had higher OD values (p < or = 0.04), but no association was shown with age of tic onset, tic severity, sudden onset of tics, or presence of attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Risk ratio calculations in TS and control groups and in study subjects dichotomized for high and low putamen OD values were similar for titers of antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup analysis limited to subjects with elevated streptococcal titers, however, showed a significantly (p < or = 0.004) larger number of TS subjects with elevated OD levels. CONCLUSION: Children and adolescents with TS had significantly higher serum levels of antineuronal antibodies against putamen than did controls, but their relation to clinical characteristics and markers for streptococcal infection remains equivocal.     

Is comorbidity with ADHD a marker for juvenile-onset mania?

OBJECTIVE: To compare the characteristics and correlates of mania in referred adolescents and to determine whether attention-deficit hyperactivity disorder (ADHD) is a marker of very early onset mania. METHOD: From 637 consecutive admissions, 68 children (< or = 12 years) and 42 adolescents (> 13 years) who satisfied criteria for mania were recruited. These were compared with the 527 nonmanic referrals and 100 normal controls. RESULTS: With the exception of comorbidity with ADHD, there were more similarities than differences between the children and adolescents with mania in course and correlates. There was an inverse relationship between the rates of comorbid ADHD and age of onset of mania: higher in manic children intermediate in adolescents with childhood-onset mania, and lower in adolescents with adolescent-onset mania. CONCLUSIONS: ADHD is more common in childhood-onset compared with adolescent-onset cases of bipolar disorder, suggesting that in some cases, ADHD may signal a very early onset of bipolar disorder. Clinical similarities between the child- and adolescent-onset cases provide evidence for the clinical validity of childhood-onset mania.     

Disgust implicated in obsessive-compulsive disorder

Psychiatric classificatory systems consider obsessions and compulsions as forms of anxiety disorder. However, the neurology of diseases associated with obsessive-compulsive symptoms suggests the involvement of fronto-striatal regions likely to be involved in the mediation of the emotion of disgust, suggesting that dysfunctions of disgust should be considered alongside anxiety in the pathogenesis of obsessive-compulsive behaviours. We therefore tested recognition of facial expressions of basic emotions (including disgust) by groups of participants with obsessive-compulsive disorder (OCD) and with Gilles de la Tourette's syndrome (GTS) with an without co-present obsessive-compulsive behaviours (GTS with OCB; GTS without OCB). A group of people suffering from panic disorder and generalized anxiety were also included in the study. Both groups with obsessive-compulsive symptoms (OCD; GTS with OCB) showed impaired recognition of facial expressions of disgust. Such problems were not evident in participants with panic disorder and generalized anxiety, or for participants with GTS without obsessions or compulsions, indicating that the deficit is closely related to the presence of obsessive-compulsive symptoms. Participants with OCD were able to assign words to emotion categories without difficulty, showing that their problem with disgust is linked to a failure to recognize this emotion in others and not a comprehension or response criterion effect. Impaired recognition of disgust is consistent with the neurology of OCD and with the idea that abnormal experience of disgust may be involved in the genesis of obsessions and compulsions.     

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects

OBJECTIVE: The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. METHOD: The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. RESULTS: Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. CONCLUSIONS: Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.     

Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy

OBJECTIVE: To evaluate the pharmacokinetics, safety, and efficacy of sertraline in children (6 to 12 years old) and adolescents (13 to 17 years old). METHOD: Children (n = 29) and adolescents (n = 32) with major depression, obsessive-compulsive disorder (OCD), or both received a single dose of 50 mg of sertraline followed, 1 week later, by 35 days of sertraline treatment as follows: (1) either a starting dose of 25 mg/day titrated to 200 mg/day in 25-mg increments or (2) a starting dose of 50 mg/day titrated to 200 mg/day in 50-mg increments. Sertraline and desmethylsertraline pharmacokinetics were determined approximately weekly, and efficacy measures were assessed before drug administration and at the end of treatment. RESULTS: Mean area under the plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and elimination half-life (t1/2) for sertraline and desmethylsertraline were similar to previously reported adult values. No titration-dependent pharmacokinetic or safety differences were seen. While Cmax and AUC0-24 were greater for children versus adolescents, these differences disappeared after parameters were normalized for body weight. Sertraline was well tolerated in both children and adolescents, with adverse experiences similar to those previously reported by adult patients. Efficacy measurements indicated improvement (p < .001) in depression and OCD symptomatology. CONCLUSIONS: Sertraline can be safely administered to pediatric patients using the currently recommended adult titration schedule.     

Use of atypical neuroleptics in child and adolescent psychiatry

BACKGROUND: This article reviews the published clinical experience with atypical neuroleptics in children and adolescents. METHOD: A computerized literature search was conducted (MEDLINE, 1974-1998) to retrieve all reports on the use of atypical neuroleptics in children and adolescents. A hand search was performed as well. All relevant clinical data were collated by type of drug. RESULTS: We found 5 blind placebo-controlled clinical trials (105 patients), 24 open-label clinical trials (387 patients), and 33 case series (115 patients) describing the use of the atypical neuroleptics clozapine, risperidone, olanzapine, sulpiride, tiapride, amisulpride, remoxipride, and clothiapine in children and adolescents. Some of these agents, especially clozapine, risperidone, and olanzapine, were found to be efficacious in the treatment of schizophrenia, bipolar disorders, and pervasive developmental disorders. The role of atypical neuroleptics as augmenters of serotonin reuptake inhibitors in obsessive-compulsive disorder is unclear. Risperidone appears to possess anti-tic properties in patients with Tourette's disorder. CONCLUSION: The most convincing evidence of the efficacy of atypical neuroleptics in children and adolescents concerns clozapine in the treatment of schizophrenia. Data on other atypical neuroleptics in other disorders are still sparse, and further research is needed. Some of the atypical neuroleptics may become the first-line treatment for childhood schizophrenia and pervasive developmental disorders.     

A computer-administered version of the Yale-Brown Obsessive-Compulsive Scale.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was converted to an interactive computer-administered format. To examine its utility, the computer version of the Y-BOCS was administered in a design counterbalanced with the clinician-administered version to a sample of patients with obsessive-compulsive disorder (OCD), patients with other anxiety disorders, and nonpatient controls. The computer-administered version of the Y-BOCS correlated highly with the clinician-administered version, especially in the OCD sample, and showed equal ability to distinguish OCD patients from Ss in the other 2 groups. It was also well understood and liked by Ss, who showed no preference for the clinician interview over the computer interview. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characteristics of 34 adults with psychogenic excoriation

BACKGROUND: Psychogenic excoriation, characterized by excessive scratching or picking of the skin, is not yet recognized as a symptom of a distinct DSM-IV disorder. The purpose of this study was to provide data regarding the demographics, phenomenology, course of illness, associated psychiatric comorbidity, and family history of subjects with psychogenic excoriation. METHOD: Thirty-four consecutive subjects were recruited from an outpatient dermatology practice and by advertisement. Subjects completed the Structured Clinical Interview for DSM-IV augmented with impulse control disorder modules, the Yale-Brown Obsessive Compulsive Scale, and a semistructured interview for family history, demographic data, and clinical features. RESULTS: Most subjects were women who described a mean age at onset of 38 years and a chronic course. Subjects excoriated multiple sites, most frequently the face. The behavior caused substantial distress and dysfunction. All 34 subjects met criteria for at least 1 comorbid psychiatric disorder, with a mood disorder the most common. Family histories were notable for depressive disorders and psychoactive substance use disorders. Most subjects experienced both mounting tension before excoriation and relief after excoriation as in impulse control disorders. A minority of subjects excoriated skin as part of obsessive-compulsive disorder. Body dysmorphic disorder with preoccupation about the skin's appearance precipitated excoriation in about a third of subjects. CONCLUSION: Psychogenic excoriation is chronic, involves multiple sites, and is associated with a high rate of psychiatric comorbidity. The behavior associated with the excoriation is heterogeneous and spans a compulsive-impulsive spectrum. Most subjects in this sample described features of an impulse control disorder.     

Pharmacotherapy for obsessive-compulsive disorder

BACKGROUND: Pharmacotherapy for obsessive-compulsive disorder (OCD) was seldom beneficial before clomipramine, a potent selective serotonin reuptake inhibitor (SSRI), became available. Subsequent progress in pharmacotherapy for OCD has increased the possibility of effective treatment for most sufferers. METHOD: Randomised controlled trials of pharmacotherapy for OCD were reviewed, as well as reports of beneficial pharmacotherapy found in open trials and case reports. RESULTS: SSRIs are well-tolerated by patients with OCD, even in large doses. Proserotonergic augmentation is seldom helpful but antipsychotic augmentations seem beneficial for many OCD patients with comorbid tics. CONCLUSIONS: Potent SSRIs are the pharmacotherapy of choice for OCD, with a more limited role reserved for monoamine oxidase inhibitors. If one SSRI is ineffective, others may be beneficial. Non-drug therapies are also important in OCD: behaviour therapy is frequently helpful but infrequently available and neurosurgery is sometimes helpful when all other treatments have failed.     

The Children's Yale-Brown Obsessive-Compulsive Scale: Item Structure in an Outpatient Setting.

The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is one of the most popular measures of symptom severity for childhood obsessive-compulsive disorder (OCD). This study describes the factor structure of the CY-BOCS. A total of 233 children diagnosed with OCD were evaluated with the CY-BOCS. The results indicated that 2 alternate 2-factor solutions (obsessions and compulsions; severity and disturbance) fit the data set best. The results also suggested that items assessing resistance to obsessions and compulsions provide unreliable evaluations of these symptoms in children with OCD. Recommendations for modifications to the CY-BOCS as well as clinical applications and for future research with the measure are made. (PsycINFO Database Record (c) 2010 APA, all rights reserved)