Biomedical subjects

Michael R Liebowitz

Publications and source records attributed to Michael R Liebowitz.

36 records · Page 2Linked to original sources

PubMed2004

Psychobiological dysregulation in violence-exposed mothers: salivary cortisol of mothers with very young children pre- and post-separation stress.

UNLABELLED: To understand the determinants of frightening/frightened and other atypical maternal behavior, the authors studied a sample of 41 inner-city mothers of very young children (ages 8-50 months), the mothers of whom had lifetime histories of interpersonal violent trauma (i.e., physical or sexual abuse, and domestic violence) and related posttraumatic stress. METHOD: The authors measured (1) maternal salivary cortisol levels before and 30 minutes after a videotaped play paradigm with their children, involving two separations and reunions; and (2) cortisol reactivity 30 minutes after separation stress. Data were analyzed using Pearson bivariate correlations, ANOVA, and multiple linear regressions. RESULTS: Salivary cortisol "baseline" values were significantly negatively correlated with childhood interpersonal violent trauma severity (i.e., trauma severity prior to age 16). However, cortisol reactivity was not significantly correlated with interpersonal violent trauma severity at this level of analysis. Although baseline salivary cortisol values were not significantly correlated with current overall psychiatric or depressive symptoms, they were negatively correlated with severity of current posttraumatic stress symptoms (PTSS) and with dissociative symptoms. Neither dimensions of negativity nor distortion of maternal attributions showed any significant association with prestress or poststress salivary cortisol levels. Salivary cortisol baseline was negatively correlated with atypical maternal behavior via measurement of the level of disrupted communication, at a trend-level of significance. CONCLUSIONS: Violent trauma-associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may be a marker for increased risk for intergenerational transmission via parenting behavior with young children. Low salivary cortisol prior to separation stress and blunted cortisol reactivity to separation may also be markers for posttraumatic stress.

Adult↗

PubMed2004

Overview of panic and social anxiety disorders.

Panic disorder and social anxiety disorder are often-overlooked but debilitating disorders that share some common symptoms and treatments. Patients with panic disorder experience unexpected panic attacks and then worry about having more attacks. Those with social anxiety disorder fear doing or saying something embarrassing in social situations. The prevalence of these conditions is about 3% for panic disorder and 13% for social anxiety disorder in the United States and is higher in women than in men. Both disorders are thought to have a familial link and to be related to dysregulation of neurotransmitter systems. Panic and social anxiety disorders are often comorbid with other psychiatric disorders. Medication treatment and/or cognitive-behavioral therapy might need to be continued over the long term to prevent relapse.

Comorbidity↗

PubMed2003

Serotonin transporters in obsessive-compulsive disorder: a positron emission tomography study with [(11)C]McN 5652.

BACKGROUND: Serotonergic abnormalities have been hypothesized to contribute to obsessive-compulsive disorder (OCD). This study examined whether brain serotonin transporter (SERT) availability is altered in OCD using positron emission tomography (PET) and the SERT PET radiotracer [(11)C]McN 5652. METHODS: Eleven OCD subjects, free of psychiatric medications and comorbid depression, and 11 matched healthy control subjects underwent PET scans following injection of [(11)C]McN 5652 and magnetic resonance imaging (MRI) scans. Total distribution volumes (V(T)) were derived by kinetic analysis (one tissue compartment model) using the arterial input function. Two measures of SERT availability were computed: binding potential (BP) and specific to nonspecific partition coefficient (V(3)"). Groups were compared using region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps; ROIs were selected based on their relatively high SERT density and included subcortical (dorsal caudate, dorsal putamen, ventral striatum, midbrain, thalamus) and limbic (hippocampus, amygdala, anterior cingulate cortex) regions. RESULTS: No significant group differences were observed in [(11)C]McN 5652 BP or V(3)" in the ROIs. No significant group differences were detected in the voxelwise analysis of BP or V(3)" maps. CONCLUSIONS: OCD without comorbid depression, may not be associated with major changes in SERT availability in subcortical and limbic regions.

Adolescent↗

PubMed2003

Pharmacological treatment of social anxiety disorder: a meta-analysis.

Placebo-controlled trials have evaluated the efficacy of several medications in the treatment of social anxiety disorder but information regarding their relative efficacy is lacking. We compared the efficacy of medications systematically studied for the treatment of social anxiety disorder using meta-analytic techniques. The methodology included a database search of articles published between January 1980 and June 2001 and manual searches of bibliographies in published manuscripts. Trials were included if they reported outcome data on the Liebowitz Social Anxiety Scale (LSAS) or a categorical measure of responder status. Data were extracted independently by two authors. The Q statistic was used to assess homogeneity across trials. All analyses were conducted using intent-to-treat data. There was substantial heterogeneity across trials. The medications with largest effect sizes were phenelzine [effect size, 1.02; 95% Confidence Interval (CI), 0.52-1.52], clonazepam (effect size, 0.97; 95% CI, 0.49-1.45), gabapentin (effect size, 0.78; 95% CI, 0.29-1.27), brofaromine (effect size, 0.66; 95% CI, 0.38-0.94), and the selective serotonin reuptake inhibitors (SSRIs; effect size, 0.65; 95% CI, 0.50-0.81). There were no statistically significant differences between medications or medication groups. However, formal methods of interim monitoring adapted for meta-analyses suggested strongest evidence of efficacy for SSRIs and brofaromine. Several medications are efficacious for the treatment of social anxiety disorder. The stability of the SSRI effect size estimate in conjunction with other evidence for safety and tolerability and their ability to treat comorbid conditions supports the use of SSRIs as the first-line treatment. Direct comparisons of SSRIs vs. other promising medications deserve consideration.

Acetates↗

PubMed2003

The experience of disability and quality of life in social anxiety disorder.

Although disability is a concept most often associated with role dysfunction, and quality of life is most often associated with life satisfaction, these terms are frequently used interchangeably in the literature. In contrast, this study proposes that disability and quality of life are independent but related constructs. Additionally, we propose that disability partially mediates the relationship between symptoms and quality of life. That is, greater symptoms are associated with more impairment, which is, in turn, associated with less satisfaction with one's life. Ninety-six individuals with social anxiety disorder were given measures of social anxiety symptoms, disability, and quality of life. The results of the study suggest that disability and quality of life are, in fact, distinct concepts, and the experience of disability partially mediates the relationship between a patient's experience of symptoms and his or her perceived life satisfaction.

Anxiety Disorders↗

PubMed2003

Citalopram treatment of social anxiety disorder with comorbid major depression.

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.

Adult↗

PubMed2003

The evidence-based pharmacological treatment of social anxiety disorder.

Social anxiety disorder (SAD) is a highly prevalent and often disabling disorder. This paper reviews the pharmacological treatment of SAD based on published placebo-controlled studies and published meta-analyses. It addresses three specific questions: What is the first-line treatment of SAD? How long should treatment last? What should be the management of treatment-resistant cases? Based on their efficacy for SAD and common comorbid disorders, tolerability, and safety, SSRIs should be considered as the first-line treatment for most patients. Less information is available regarding the optimal length of treatment, although individuals who discontinue treatment after 12-20 wk appear more likely to relapse than those who continue on medication. Even less empirical evidence is available to support strategies for treatment-resistant cases. Clinical experience suggests that SSRI non-responders may benefit from augmentation with benzodiazepines or gabapentin, or from switching to MAOIs, RIMAs, benzodiazepines or gabapentin. Cognitive-behavioural therapy may also be a helpful adjunct or alternative.

Anti-Anxiety Agents↗

PubMed2003

The Liebowitz social anxiety scale for children and adolescents: an initial psychometric investigation.

OBJECTIVE: To examine the psychometric properties of a newly developed clinician rating scale, the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA). METHOD: A total of 154 children and adolescents participated in an assessment consisting of a diagnostic interview, the LSAS-CA, and other measures of psychopathology and impairment. Sixty-one of these children also participated in a second LSAS-CA administration, by a different rater blind to diagnosis, within 7 days of the initial assessment. RESULTS: High internal consistency (alpha =.90-.97 for full sample and.83-.95 for social phobia group) and test-retest reliability (intraclass correlation coefficient = 0.89-0.94) were obtained for LSAS-CA total and subscale scores. LSAS-CA scores had stronger associations with measures of social anxiety and general impairment than with a measure of depression. Subjects with social anxiety disorder had significantly higher LSAS-CA scores than subjects with other anxiety disorders and healthy controls. A LSAS-CA cutoff score of 22.5 represented the best balance of sensitivity and specificity when distinguishing between individuals with social phobia and normal controls, whereas a cutoff of 29.5 was optimal for distinguishing social phobia from other anxiety disorders. CONCLUSION: Initial findings suggest that the LSAS-CA is a reliable and valid instrument for the assessment of social anxiety disorder.

Adolescent↗

PubMed2003

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↗

PubMed2003

Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study.

BACKGROUND: Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults. METHOD: After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score </= 2. Data were collected in 2000 and 2001. RESULTS: 211 patients were randomly assigned to sertraline (intent-to-treat [ITT] sample, 205), and 204 patients, to placebo (ITT sample, 196). At week 12, sertraline produced a significantly greater reduction in LSAS total score compared with placebo (mean last-observation-carried-forward [LOCF] change from baseline: -31.0 vs. -21.7; p =.001) and a greater proportion of responders (CGI-I score </= 2: 55.6% vs. 29% among week 12 completers and 46.8% vs. 25.5% in the ITT-LOCF sample; p <.001 for both comparisons). Sertraline was well tolerated, with 7.6% of patients discontinuing due to adverse events versus 2.9% of placebo-treated patients. CONCLUSION: The results of the current study confirm the efficacy of sertraline in the treatment of severe social anxiety disorder.

Adult↗

PubMed2002

A pilot study of noradrenergic and HPA axis functioning in PTSD vs. panic disorder.

The biological literature in the anxiety disorders has focused on comparisons between patient groups and normal volunteers, with relatively little comparative study of the anxiety disorders. We therefore conducted this pilot study to compare a group of patients with post-traumatic stress disorder (PTSD) (n = 7) to a contiguously studied panic disorder group (n = 17) and healthy control subjects (n = 16) on baseline levels of cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG), and response to clonidine challenge. Despite the small sample size, highly significant differences were found on the following measures: PTSD patients had lower cortisol, lower MHPG, reduced MHPG volatility to clonidine challenge, and marginally reduced cortisol volatility compared to patients with panic disorder. These biological findings support existing clinical, epidemiologic, family study, and clinical trial findings that distinguish these two disorders as distinct syndromes.

Adolescent↗

PubMed2002

Pharmacotherapy of social anxiety disorder.

Over the last few years, a number of medications have demonstrated their efficacy in the acute treatment of social anxiety disorder. At present, selective serotonin reuptake inhibitors probably constitute the first line treatment, based on their safety, tolerability, and efficacy in the treatment of social anxiety disorder and common comorbid conditions. Data from single trials suggest that clonazepam, bromazepam, and gabapentin may have efficacy similar to the serotonin reuptake inhibitors, but further studies are needed to confirm these findings. The monoamine oxidase inhibitor phenelzine appears to be at least as efficacious as these other agents, but should be reserved for cases that fail to respond to these safer medications. Among the reversible inhibitors of monoamine oxidase A, brofaromine may also be an effective drug, while moclobemide appears to be less potent. Future research directions should include delineating ways to achieve remission (as opposed to response); developing strategies for augmenting partial responders and treating nonresponders to first line approaches; studying the long-term response to medication and prevention of relapse when medication is discontinued; clarifying ways to integrate psychosocial and pharmacological treatment approaches; developing predictors of which patients do best with which treatments; and the treatment of social anxiety disorder in children and adolescents.

Humans↗

PubMed2002

The social anxiety spectrum.

Social anxiety disorder is well suited to the spectrum concept because it has trait-like qualities of early onset, chronicity, and no empirically derived threshold that demarcates normal from clinically significant trait social anxiety. Social anxiety disorder has been shown to respond to relatively specific pharmacologic and cognitive-behavioral therapies, which makes identification of other conditions that may lie on the social anxiety disorder spectrum important because of possible treatment implications. Biologic markers associated with social anxiety disorder also may be shared by similar but nonidentical traits, such as behavioral inhibition and detachment. Clarification of the trait spectrums associated with specific biologic systems offers an opportunity for improving the understanding of the origin of these conditions. Strong evidence exists that at least some forms of shyness, avoidant personality disorder, and selective mutism lie on a social anxiety disorder spectrum. For several other disorders that share a prominent focus on social comparison, significant subgroups of patients seem to have features of social anxiety disorder. These disorders include major depression (especially the atypical subtype), body dysmorphic disorder, and eating disorders. Several other disorders marked by social dysfunction or inhibition, including substance use disorders (especially alcoholism), paranoid disorder, bipolar disorder, autism, and Asperger's disorder, also may show some overlap with social anxiety disorder features (e.g., social anxiety as a cause or complication of substance abuse, social avoidance in paranoid disorder, social disinhibiton in bipolar disorder, and social communication deficits in autism and Asperger's disorder). Social anxiety disorder also is associated with other anxiety disorders in general and other phobias in particular. In respect to traits, a growing body of evidence links behavioral inhibition to the unfamiliar to a social anxiety disorder spectrum with some specificity. Biologic measures of dopamine system hypoactivity have been linked to social anxiety disorder, trait detachment, and general deficits in reward and incentive function. It remains to be clarified, however, whether this brain system function is best characterized by a social anxiety disorder spectrum or some variant that incorporates social reward deficits or social avoidance behavior. Social anxiety disorder, shyness, and behavioral inhibition all seem to have a genetic component, but more research is needed to attempt to identify a more specifically heritable temperament associated with these conditions. Finally, the emergent concept of a social anxiety spectrum needs maturation. Although the notion of a single social anxiety disorder spectrum currently has some clinical use, the authors believe that exclusive focus on the notion of a single continuum with two extremes--from social disinhibition in mania to the most severe form of social anxiety, avoidant personality disorder--is premature and limiting in respect to etiologic research. An alternative approach is to conceptualize multiple, probably overlapping spectra in this area of social psychopathology. Individual dimensions might be based on various core phenomenologic, cognitive, or biologic characteristics. A bottom-up biologic approach holds promise for identifying spectra with a common etiology that might respond to specific treatments. Taking a pluralistic view of the concept of spectrum at this stage may help accelerate our understanding of social anxiety and related disorders.

Brain↗

PubMed2002

Screening for social anxiety disorder in the clinical setting: using the Liebowitz Social Anxiety Scale.

OBJECTIVE: We sought to determine optimal cutoff values for the Liebowitz Social Anxiety Scale (LSAS) total and subscale scores for the diagnosis of social anxiety disorder (SAD) and designation of the generalized subtype of SAD. METHOD: Three hundred and sixty-four patients from a multi-site sample who met criteria for SAD according to structured diagnostic interview, 262 of whom met criteria for the generalized subtype, and 34 control participants free of current Axis I disorders participated in this study. All participants were given the Liebowitz Social Anxiety Scale by an independent assessor. RESULTS: Receiver Operating Characteristics analysis revealed that the LSAS performed well in identifying individuals who met criteria for SAD and for the generalized subtype of SAD. Cutoffs of 30 for SAD and 60 for its generalized subtype on the LSAS total score represented the best balance of specificity and sensitivity. CONCLUSIONS: These findings provide support for the use of the Liebowitz Social Anxiety Scale for the identification of individuals with SAD and its generalized subtype in clinical settings. Identification of patients with SAD should increase the percentage of these patients who receive appropriate treatment for this impairing disorder.

Adolescent↗

PubMed2002

Fluoxetine in children and adolescents with OCD: a placebo-controlled trial.

OBJECTIVE: To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD). METHOD: Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample. RESULTS: Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p <.05). No patient terminated the study because of adverse medication effects. CONCLUSION: Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop.

Adolescent↗

PubMed2002

A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder.

BACKGROUND: This multicenter, double-blind, placebo-controlled study was carried out to determine the effectiveness and safety of various daily dosages of paroxetine for the treatment of generalized social anxiety disorder. METHOD: A 1-week, single-blind, placebo run-in was followed by 12 weeks of double-blind treatment. 384 eligible patients meeting DSM-IV criteria for social anxiety disorder were randomly assigned to receive paroxetine, 20 (N = 97), 40 (N = 95), or 60 mg (N = 97), or placebo (N = 95) once daily in a 1:1:1:1 ratio. Primary efficacy variables included mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and proportion of patients exhibiting a therapeutic response (defined as a Clinical Global Impressions-Global Improvement scale [CGI-1] score of 1 or 2). RESULTS: In the last-observation-carried-forward analyses, patients treated with paroxetine, 20 mg/day, had significantly greater improvement on mean LSAS total scores compared with those receiving placebo (p < .001), while the incidence of responders, based on the CGI-I rating, was significantly greater with paroxetine, 40 mg/day, than with placebo (p = .012). Patients treated with paroxetine, 20 and 60 mg, also had significantly better responses on the social item of the Sheehan Disability Scale than did patients treated with placebo (p < .019). The completer analyses showed a significant difference between the placebo group and the 20-mg and 40-mg paroxetine groups on LSAS total score and rate of response (p < or = .006). There were no serious adverse experiences attributed to paroxetine treatment. CONCLUSION: Paroxetine, 20 mg/day, is an effective and safe treatment for patients with generalized social anxiety disorder and significantly improves social anxiety, avoidance of social interactions, social disability, and overall clinical condition. Further data analyses are needed to determine whether more specific guidelines for paroxetine dosage escalation in social anxiety disorder can be drawn.

Adolescent↗

PubMed2002

Social anxiety disorder and generalized anxiety disorder: serotonergic and dopaminergic neurocircuitry.

Awareness that an amygdala-based fear circuit plays a crucial role in mediating fear conditioning as well as anxiety symptoms is growing. The efficacy of selective serotonin reuptake inhibitors in certain anxiety disorders has been argued to reflect their ability to modulate this circuit. Whether additional neurocircuits play a differentiating role in specific anxiety disorders, such as social anxiety disorder and generalized anxiety disorder (GAD), is an ongoing subject of investigation. A review of the literature suggests that in social anxiety disorder, dopaminergically mediated striatal circuits may also be important, while in GAD, there may be abnormalities of prefrontal areas. Future work will undoubtedly clarify how genetic and environmental factors interact to fashion the neurocircuitry that mediates anxiety symptoms.

Amygdala↗

PubMedDate not supplied

An open trial of fluvoxamine for hypochondriasis.

The authors conducted a 12-week, open-label trial of fluvoxamine among 18 patients with DSM-IV hypochondriasis. Response was defined as a physician-rated CGI improvement rating of at least "much improved." Four patients discontinued during the 2-week placebo run-in phase. Among 14 patients given fluvoxamine, the response rate was 72.7% (N=8 of 11) for those completing at least 6 weeks of the trial (minimum-treatment analysis) and 57.1% (N=8 of 14) for the intent-to-treat analysis; these are comparable to rates reported previously for fluoxetine. Significant improvement was also noted on each of the self-report and physician-administered hypochondriasis measures. Fluvoxamine was also well tolerated. A controlled trial is needed.

Adult↗