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Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder.

OBJECTIVE: No consistent predictors of outcome have been identified for the pharmaco-therapy of obsessive-compulsive disorder (OCD). Recent factor analytic studies have identified meaningful symptom dimensions that may be related to response to serotonin reuptake inhibitors and other treatments. METHOD: A total of 354 outpatients with primary OCD were administered the Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 main symptom categories were factor analyzed by using principal components analysis. The identified symptom dimensions were then entered into multiple regression models as outcome predictors of response to serotonin reuptake inhibitors and placebo response in a group of 150 nondepressed subjects who completed six double-blind, placebo-controlled trials with a serotonin reuptake inhibitor (clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine). Eighty-four patients received a serotonin reuptake inhibitor and 66, placebo. RESULTS: The principal components analysis identified five factors that explained 65.5% of variance in outcome: symmetry/ordering, hoarding, contamination/cleaning, aggressive/checking, and sexual/religious obsessions. Serotonin reuptake inhibitors were significantly superior to placebo on all outcome measures. Initial severity of OCD was related to greater posttreatment severity of OCD. Higher scores on the hoarding dimension predicted poorer outcome following treatment with serotonin reuptake inhibitors, after control for baseline severity. No predictors of placebo response were identified. Exclusion of clomipramine did not modify the overall results, suggesting a cross-serotonin reuptake inhibitor effect. CONCLUSIONS: The identified symptom dimensions are largely congruent with those identified in earlier reports. Patients with OCD vary in their response to treatment with serotonin reuptake inhibitors. The presence of hoarding obsessions and compulsions is associated with poorer response to serotonin reuptake inhibitors.

Adolescent↗

A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder.

OBJECTIVE: Reductions in the level of N-acetylaspartate within subcortical structures of patients with obsessive-compulsive disorder (OCD) have been reported in several studies. However, there have been, as yet, no reports regarding N-acetylaspartate levels in the prefrontal cortex of adult drug-naive OCD patients. The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to investigate regional N-acetylaspartate level abnormalities and changes after 12 weeks of pharmacotherapy with citalopram in drug-naive OCD patients. METHOD: Thirteen drug-naive OCD patients and 13 age- and sex-matched healthy comparison subjects were included in this study. N-acetylaspartate levels (obtained from ratios of N-acetylaspartate with creatine, choline, and creatine plus choline) in the prefrontal cortex, parietal cortex, anterior cingulate, posterior cingulate, frontal white matter, and parietal white matter were measured by (1)H-MRSI. In OCD patients, measurements were taken before and after 12 weeks of citalopram treatment. Correlations between N-acetylaspartate concentrations in regions of interest and clinical measures were also assessed. RESULTS: Drug-naive OCD patients exhibited significantly lower N-acetylaspartate levels in the prefrontal cortex, frontal white matter, and anterior cingulate at baseline than did comparison subjects. Significant increases in N-acetylaspartate level were detected in the prefrontal cortex and frontal white matter in OCD patients after 12 weeks of citalopram treatment. CONCLUSIONS: These data suggest that reductions in neuronal viability occur in the frontal region of OCD patients and that these reductions may be partly reversible.

Adult↗

Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder.

OBJECTIVE: The authors conducted a meta-analysis of published randomized, controlled medication trials in children and adolescents with obsessive-compulsive disorder (OCD) to assess evidence for differential efficacy based on type of drug, study design, and outcome measure. METHOD: A systematic literature search was performed for articles pertaining to the pharmacological treatment of pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores with standard deviations reported in each study were included in the analyses. Effect sizes for dependent measures were expressed as standardized mean differences. The analysis included data on efficacy for four selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine, four study designs, four dependent outcome measures, and two types of outcome scores (change and posttreatment scores). Multivariate regression was performed to assess the degree to which the effect sizes varied with the methodological features of each study. RESULTS: Twelve studies with a total of 1,044 participants met all inclusion criteria for the analysis. The pooled standardized mean difference for the results of all studies was 0.46 and showed a highly significant difference between drug and placebo treatment. Only one of the four outcome measures evaluated was not sensitive to change with treatment. A multivariate regression analysis of drug effect with other variables controlled showed that clomipramine was significantly superior to each of the SSRIs but that the SSRIs were comparably effective. CONCLUSIONS: Although highly significant, the overall effect sizes for medication were modest. Similarities and differences between the variables studied that emerged in the meta-analysis may have implications for both clinical care and future research.

Adolescent↗

The relation between eating disorders and components of perfectionism.

OBJECTIVE: The authors' goal was to explore the relation between perfectionism and psychopathology, including eating disorders. METHOD: Using logistic regression, the authors calculated odds ratios for the associations between perfectionism subscale scores and psychiatric disorders in 1,010 female twins who completed the Multidimensional Perfectionism Scale and participated in diagnostic interviews. RESULTS: Elevated concern over mistakes was associated with anorexia and bulimia nervosa but not with other psychiatric disorders. Doubts about actions was associated with eating and anxiety disorders. Multivariable models confirmed that higher scores on the subscales for concern over mistakes and doubts about actions were most strongly associated with eating disorders. CONCLUSIONS: The aspect of perfectionism captured by scores on a subscale measuring concern over mistakes may be particularly associated with eating disorders and not generically predictive of psychopathology.

Adult↗

A multidimensional model of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. This heterogeneity can reduce the power and obscure the findings from natural history studies to genome scans, neuroimaging, and clinical trials. The authors review the evidence supporting a multidimensional model of OCD. METHOD: Computerized and manual literature searches were performed to identify factor-analytic studies of obsessive-compulsive symptoms before data from disciplines that bear on the potential usefulness of these dimensions were considered. Selection criteria included the novelty and importance of studies and their relevance to outcomes of interest to well-informed mental health professionals. RESULTS: Twelve factor-analytic studies involving more than 2,000 patients were identified that consistently extracted at least four symptom dimensions: symmetry/ordering, hoarding, contamination/cleaning, and obsessions/checking. These dimensions were associated with distinct patterns of comorbidity, genetic transmission, neural substrates, and treatment response. The evidence supporting the hoarding dimension is particularly robust. CONCLUSIONS: The complex clinical presentation of OCD can be summarized with a few consistent, temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping syndromes that may 1) coexist in any patient, 2) be continuous with normal obsessive-compulsive phenomena, and 3) extend beyond the traditional nosological boundaries of OCD. Although the dimensional structure of obsessive-compulsive symptoms is imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. The need for a dimensional rating scale and suggestions for future research aimed at reducing the burden of this disorder are discussed.

Brain↗

Adaptive, emotional, and family functioning of children with obsessive-compulsive disorder and comorbid attention deficit hyperactivity disorder.

OBJECTIVE: The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains. METHOD: The study group included 287 children and adolescents (191 boys, 96 girls) ages 7-18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment. RESULTS: The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD. CONCLUSIONS: Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.

Adaptation, Psychological↗

Marital therapy of couples in which the husband is a physician.

This paper is concerned with the therapeutic problems posed by the troubled "medical" marriage. Based on the authors' clinical experiences, certain common characteristics of these marriages are identified. Obstacles to early referral such as self-diagnosis and self-treatment are discussed, two illustrative case vignettes are presented, and therapeutic recommendations are outlined.

Affective Symptoms↗

Psychogenic impotence and the black man's burden.

Clinical material is presented on a single case of impotence in a middle-aged black man. The symbolic meanings of the symptom in terms of the patient's aggression, feelings about his racial self-image, and the options that allow for male identity are discussed, along with some aspects of an interracial treatment situation in these changing times.

Adult↗

Psychotherapy of the obsessional.

Obsessional defenses require a confronting, active therapist in order to break through the intellectualized, ritualized, and highly distracting productions of the patients. The tendency to obfuscate through details and rigid adherence to the instructions demands a loose, flexible, and direct interaction from a therapist who is not too obessional and willing to forego his own perfectionistic expectations from therapy.

Anxiety↗

Patients' reactions to humorous interventions in psychotherapy.

This study explores the preference of patients for humorous or nonhumorous therapist interventions. Hysterical, obsessive, and depressive patients were presented with three functional kinds of humorous interventions: emotional confrontation, anxiety reduction and perspective development. The data indicate that the patients consistently favored the nonhumorous interventions, but the degree of this preference varied according to personality style. Obsessive patients stood out in their ardent repudiation of humorous interventions. The results suggest that the desirability of utilizing humor in therapy depends on a multiplicity of parameters.

Adult↗

Item-by-item factor analysis of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist.

Clinical subtypes of obsessive-compulsive disorder may have differing pathophysiological mechanisms and treatment outcomes. The subtypes identified by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom Checklist, clustered by clinical consensus, have never been subject to statistical validation. A factor analysis using a sample of 160 patients with OCD was conducted to determine whether factor analytically derived categories are identical to extant clinically determined categories. Our analysis revealed that the contamination subtype of the Y-BOCS Symptom Checklist contains two distinct subgroups: one relating to discomfort and the other to fear of harm. If replicated on a larger scale, the finding of new subtype groupings would have important implications for future research in obsessive-compulsive disorder.

Adolescent↗

Neurological soft signs as predictors of treatment response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.

Double-Blind Method↗

A pilot follow-up study of childhood soft signs and the development of adult psychopathology.

A subgroup of subjects (4 of 12) with childhood soft signs and adolescent anxiety-withdrawal disorders were followed up into adulthood and assessed for soft signs and psychiatric diagnoses. These subjects continued to have soft-sign abnormalities and most had adult anxiety or affective disorders, including obsessive-compulsive disorder (OCD). In contrast, control subjects with childhood soft signs but no adolescent anxiety disorders had fewer soft signs at follow-up and no discrete adult anxiety or affective disorders, but they did have obsessive-compulsive symptoms that did not meet criteria for OCD.

Adolescent↗

Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.

Administration, Oral↗