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Biomedical subjects

W K Goodman

Publications and source records attributed to W K Goodman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Symptoms of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder. METHOD: This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N = 208 and N = 98). A principal-components factor analysis with varimax rotation was performed, followed by a series of other exploratory analyses. RESULTS: The two data sets yielded nearly identical results. Four factors--obsessions and checking, symmetry and ordering, cleanliness and washing, and boarding--emerged in each data set, in total accounting for more than 60% of the variance. CONCLUSIONS: Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.

Adult↗
PubMed1997

Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to determine whether combined treatment with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30 patients with obsessive-compulsive disorder whose symptoms were refractory to SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There were no significant differences between the adjunctive desipramine and placebo groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine.

1-Naphthylamine↗
PubMed1997

A severity rating scale for body dysmorphic disorder: development, reliability, and validity of a modified version of the Yale-Brown Obsessive Compulsive Scale.

The authors developed the Yale Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS), a 12-item semistructured clinician-rated instrument designed to rate severity of body dysmorphic disorder (BDD). The scale was administered to 125 subjects with BDD, and interviews with 15 subjects were rated by 3 other raters. Test-retest reliability was assessed in 30 subjects. Other scales were administered to assess convergent and discriminant validity, and sensitivity to change was evaluated in a study of fluvoxamine. Each item was frequently endorsed across a range of severity. Good interrater reliability, test-retest reliability, and internal consistency were obtained. BDD-YBOCS scores correlated with global severity scores but not with a measure of general psychopathology; they were modestly positively correlated with depression severity scores. Three factors accounted for 59.6 percent of the variance. The scale was sensitive to change in BDD severity. The BDD-YBOCS appears to be a reliable and valid measure of BDD severity and is a suitable outcome measure in treatment studies of BDD.

Adult↗
PubMed1997

Fluvoxamine in the treatment of obsessive-compulsive disorder and related conditions.

The mainstay of the pharmacologic treatment of obsessive-compulsive disorder (OCD) is a 10- to 12-week trial of a potent serotonin reuptake inhibitor (SRI) at an adequate dose. Double-blind, placebo-controlled trials have established the anti-obsessive-compulsive (OC) efficacy of five different SRIs. One of the most thoroughly studied of these SRIs is fluvoxamine, the focus of this article. Fluvoxamine's pharmacologic and pharmacokinetic properties, its efficacy, and guidelines for its clinical use in OCD and related disorders are briefly reviewed. Potential drug-drug interactions are discussed and placed in clinical perspective. The management of common SRI-induced side effects is also addressed. Recent comparative studies suggest that fluvoxamine may be equivalent in efficacy to clomipramine, yet better tolerated. Fluvoxamine shows promise in the treatment of several so-called OC-spectrum disorders, but additional controlled trials are needed.

Adolescent↗
PubMed1996

Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial.

One hundred and sixty patients with a primary diagnosis of obsessive-compulsive disorder were enrolled in a multicentre, randomized, double-blind, placebo-controlled study of fluvoxamine. After a placebo washout phase, patients were randomized to treatment with placebo or fluvoxamine (100-300 mg/day) for 10 weeks. Seventy-eight patients in each group were evaluable for efficacy. Fluvoxamine was significantly more effective than placebo as assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive (NIMH-OC) scale and the Global Improvement item of the Clinical Global Impression (CGI) scale. The percentage of patients classified as "responders" (much or very much improved according to the Global Improvement item) was also significantly higher in the fluvoxamine group from Week 6 onwards, with 33.3% of fluvoxamine-treated patients and 9.0% of those given placebo classified as "responders" at endpoint. The "responders" to fluvoxamine experienced a substantial clinical benefit as reflected in decreases in their Y-BOCS and NIMH-OC scores. Fluvoxamine was well tolerated with the majority of adverse events considered mild or moderate.

Adult↗
PubMed1995

m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: absence of symptom exacerbation.

Oral administration of the serotonin mixed agonist-antagonist meta-chlorophenylpiperazine (mCPP) at 0.5 mg/kg has been reported to exacerbate symptoms of obsessive-compulsive disorder (OCD). In an attempt to replicate these findings, double-blind behavioral and biochemical measures were obtained in 12 drug-free patients (9 men, 3 women) with OCD who received either oral mCPP (0.5 mg/kg), intravenous (IV) mCPP (0.1 mg/kg over 20 min), or placebo in random order on 3 separate test days. Neither oral nor IV mCPP had significant effects on the severity of OCD symptoms. The magnitude of the mCPP-induced plasma prolactin response and plasma mCPP levels were similar to those values obtained in other published studies in which mCPP exacerbated OCD symptoms. In contrast, both oral and IV mCPP were associated with significant increases in ratings of anxiety. These findings suggest that mCPP, whether administered by an oral or intravenous route (as a slow infusion), may not be a reliable probe for investigating obsessive-compulsive symptoms. It is possible, however, that more reproducible behavioral findings might be obtained by identifying susceptible subgroups of OCD or by including a behavioral exposure condition.

Administration, Oral↗
PubMed1995

Effects of tryptophan depletion on responses to yohimbine in healthy human subjects.

There is considerable evidence that both the norepinephrine (NE) and serotonin (5-HT) systems are involved in the regulation of human anxiety and fear responses. To assess the modulating effects of central 5-HT levels on NE function, 11 healthy human subjects were studied with placebo-controlled challenge tests involving tryptophan depletion followed by administration of the alpha-2-adrenergic antagonist yohimbine 0.4 mg/kg IV. Five of the 11 subjects reported a marked increase in feelings of nervousness (> or = 25 mm on a 100 mm analog scale) following the combination test, while 1/11 had this response to yohimbine alone. No subjects had an increase in nervousness during other control tests. The increase in nervousness after the tryptophan depletion-yohimbine test was statistically significant for the whole group, but there were no other unique changes in behavioral, physiologic or biochemical (MHPG, cortisol) variables with this test. These data are discussed in terms of possible functional interactions between the 5-HT and NE neurotransmitter systems.

Adrenergic alpha-Antagonists↗
PubMed1995

Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls.

To examine the role of noradrenergic, dopaminergic, and serotonergic mechanisms in the pathobiology of obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), concentrations of tyrosine (TYR), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the lumbar cerebrospinal fluid (CSF) of 39 medication-free OCD patients, 33 medication-free TS patients, and 44 healthy volunteers. CSF TYR concentrations were reduced (p < .05) in the OCD patients compared to the healthy subjects. CSF NE in TS patients was 55% higher than in healthy controls (p < .001) and 35% higher than in OCD patients (p < .001). After covarying for height, CSF HVA levels were reduced (p < .05) in the OCD group compared to TS patients but not compared to the normal volunteers. No mean differences in CSF MHPG, TRP, and 5-HIAA were observed in this study across the three groups. The CSF NE data support the hypothesis that noradrenergic mechanisms are involved in the pathobiology of TS. Alterations in the balance of noradrenergic, dopaminergic, and serotonergic systems are likely involved in the pathobiology of OCD.

Adolescent↗
PubMed1995

DSM-IV field trial: obsessive-compulsive disorder.

OBJECTIVE: Three issues relevant to revising the DSM-III-R criteria for obsessive-compulsive disorder were examined in a field trial: 1) the requirement that symptoms of obsessive-compulsive disorder be viewed by the patient as excessive or unreasonable, 2) the presence of mental compulsions in addition to behavioral compulsions, and 3) ICD-10 subcategories. METHOD: The authors studied symptom patterns of obsessive-compulsive disorder as well as strength of obsessive belief among 431 patients with obsessive-compulsive disorder at seven hospital outpatient clinics. Two methods of subject selection were used: consecutive entry of everyone who contacted the clinics for evaluation of obsessive-compulsive disorder and entry of patients with obsessive-compulsive disorder who had continuing contact with the clinics since before the field trial and who were still symptomatic. Primary measures were the Yale-Brown Obsessive Compulsive Scale and face-valid questions about fixity of obsessive-compulsive beliefs. RESULTS: The large majority of patients were uncertain about whether their obsessive-compulsive symptoms were unreasonable or excessive, and most had both mental and behavioral compulsions. Results on the ICD-10 subcategories were equivocal. CONCLUSIONS: The present results converge with previous findings to indicate a broad range of insight among patients with obsessive-compulsive disorder. The DSM-III-R requirement for insight should be de-emphasized in DSM-IV, and mental rituals should be included in the definition of compulsions.

Adult↗
PubMed1995

Lack of efficacy of clozapine monotherapy in refractory obsessive-compulsive disorder.

OBJECTIVE: The authors assessed the efficacy of clozapine monotherapy for adults with treatment-resistant obsessive-compulsive disorder. METHOD: Twelve adults with refractory obsessive-compulsive disorder participated in a 10-week, open-label, systematic trial of clozapine. They were assessed with the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, and the global improvement item of the Clinical Global Impression (CGI) scale. RESULTS: None of the 10 patients who completed the trial was a responder. No significant change was observed in obsessive-compulsive or depressive symptoms or in scores on the CGI global improvement item. CONCLUSIONS: These findings suggest that clozapine monotherapy is not effective for most adult patients with treatment-resistant obsessive-compulsive disorder.

Adult↗
PubMed1995

Family accommodation in obsessive-compulsive disorder.

OBJECTIVE: Family accommodation of patients with obsessive-compulsive disorder, i.e., participation in symptoms and modification of personal and family routines, was assessed in relation to family stress, functioning, and attitudes toward the patient. METHOD: Primary caretakers for 34 patients with obsessive-compulsive disorder were interviewed to assess the nature and frequency of accommodating behaviors. The caretakers also completed several measures of family functioning. RESULTS: Of the 34 spouses or parents, 30 (88.2%) reported accommodating the patient. Family accommodation correlated with poor family functioning, rejecting attitudes toward the patient, and several types of family stress. CONCLUSIONS: Family accommodation of patients with obsessive-compulsive disorder was associated with global family dysfunction and stress. This study suggests that families' efforts to accommodate patients may be intended to reduce patient anxiety or anger directed at relatives.

Adult↗
PubMed1995

A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to investigate the types of repetitive thoughts and behavior demonstrated by adults with autistic disorder and compare them with those of age- and sex-matched adults with obsessive-compulsive disorder. METHOD: Fifty consecutive patients admitted to the Yale Adult Pervasive Developmental Disorders (Autism) Clinic with a primary diagnosis of autistic disorder (DSM-III-R and DSM-IV) completed the symptom checklist of the Yale-Brown Obsessive Compulsive Scale. Types of current obsessions and compulsions were evaluated. The comparison group consisted of 50 age- and sex-matched adults with obsessive-compulsive disorder (without tics) (DSM-III-R and DSM-IV). RESULTS: Direct discriminant function analysis showed that the patients with autistic disorder could be distinguished from those with obsessive-compulsive disorder on the basis of the types of current repetitive thoughts and behavior that they demonstrated. Compared to the obsessive-compulsive group, the autistic patients were significantly less likely to experience thoughts with aggressive, contamination, sexual, religious, symmetry, and somatic content. Repetitive ordering; hoarding; telling or asking (trend); touching, tapping, or rubbing; and self-damaging or self-mutilating behavior occurred significantly more frequently in the autistic patients, whereas cleaning, checking, and counting behavior was less common in the autistic group than in the patients with obsessive-compulsive disorder. In addition, a specific subset of seven obsessive-compulsive variables from the Yale-Brown Obsessive Compulsive Scale symptom checklist was identified that reliably predicted membership in the autistic group. CONCLUSIONS: These results suggest that the repetitive thoughts and behavior characteristics of autism differ significantly from the obsessive-compulsive symptoms displayed by patients with obsessive-compulsive disorder. Future studies are warranted to assess the treatment response and neurobiological underpinnings of repetitive thoughts and behavior in patients with autism and obsessive-compulsive disorder.

Adolescent↗
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↗
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

Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls.

BACKGROUND: Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS: A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.

Adolescent↗