Faculty Bibliography

Women have a higher prevalence of generalized anxiety disorder (GAD) than do men, but few studies have assessed gender differences in response to pharmacotherapy. In this study we examined gender as a correlate of response to 6 weeks of open, prospective fluoxetine treatment in 23 men and 22 women with a primary diagnosis of GAD. There was no difference by gender in age or prevalence of mood and anxiety comorbidity; however, GAD onset occurred at a significantly younger age in women compared with men. Despite a lack of difference in baseline severity measures, women had a significantly poorer response to fluoxetine as measured by both the Hamilton Anxiety Rating Scale (HAM-A) and Clinician Global Impression-Severity Scale (CGI-S). In multivariate analyses, there was a significant interaction between age of onset and gender: men with younger age of onset and women with older age of onset exhibited poorer response on the HAM-A. These data, though limited in sample size and by the post hoc nature of our analyses, offer preliminary support that women with GAD, particularly those with a later age of onset, may have a poorer response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Larger placebo-controlled trials are needed to more definitively examine gender and treatment response in anxiety disorders.

Little is known about factors that mediate the relationship between anxiety and respiratory-related distress and disability. We hypothesized that elevations in anxiety sensitivity would be associated with greater severity of dyspnea, greater dyspnea-related avoidance, and poorer subjective assessment of health in patients with dyspnea referred for pulmonary function testing, regardless of objective evidence of pulmonary dysfunction. A total of 182 consecutive patients receiving pulmonary function tests to evaluate dyspnea were screened with a patient-rated Primary Care Evaluation of Mental Disorders and completed the Anxiety Sensitivity Index and questionnaires assessing symptom severity and avoidance. Anxiety Sensitivity Index score predicted more severe subjective dyspnea and greater dyspnea-related avoidance, even after adjustment for anxiety disorders and pulmonary dysfunction. Despite some limitations, these data provide preliminary support that strategies to identify, measure, and address high levels of anxiety sensitivity should be examined to reduce subjective distress and improve functioning for patients with dyspnea.

Little is known about cultural differences in the expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," t[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy.

BACKGROUND: Little is known about the biological mechanisms underlying the excess medical morbidity and mortality associated with mood disorders. Substantial evidence supports abnormalities in stress-related biological systems in depression. Accelerated telomere shortening may reflect stress-related oxidative damage to cells and accelerated aging, and severe psychosocial stress has been linked to telomere shortening. We propose that chronic stress associated with mood disorders may contribute to excess vulnerability for diseases of aging such as cardiovascular disease and possibly some cancers through accelerated organismal aging. METHODS: Telomere length was measured by Southern Analysis in 44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age-matched control subjects. RESULTS: Telomere length was significantly shorter in those with mood disorders, representing as much as 10 years of accelerated aging. CONCLUSIONS: These results provide preliminary evidence that mood disorders are associated with accelerated aging and may suggest a novel mechanism for mood disorder-associated morbidity and mortality.

The frequent presentation of patients with panic disorder in medical settings may, in part, be explained by the physical symptoms inherent in panic disorder. However, a number of medical disorders have symptoms that overlap with panic disorder symptoms, and elevated panic disorder prevalence is comorbid with a number of medical illnesses, including respiratory disorders, vestibular dysfunction, and hyperthyroidism and hypothyroidism. The presence of medical comorbidity complicates the identification, presentation, and treatment of panic disorder. In addition, comorbid mood disorders occur commonly and result in greater severity, poorer quality of life, and greater impairment. Recent work suggests that panic disorder occurs more commonly with bipolar disorder than major depressive disorder, resulting in substantial impairment, as well as poorer response to treatment. The implications of mood disorder and its medical comorbidity for the identification and treatment of panic disorder are discussed.

BACKGROUND: Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. METHODS: We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder (n=110) or major depressive disorder (n=92). RESULTS: Current mood state was significantly associated with ASI score (Chi-square=21.2, df=4, p=0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores (p<0.04). Current mixed state tended toward a similar association (p<0.10). LIMITATIONS: Conclusions are limited by the study's cross-sectional nature and relatively small sample size. CONCLUSIONS: These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder.

BACKGROUND: Systematic studies of children and adolescents with a diagnosis of bipolar disorder show that rates of attention-deficit/hyperactivity disorder (ADHD) range from 60% to 90%, but the prevalence and implications of ADHD in adults with bipolar disorder are less clear. METHODS: The first consecutive 1000 adults with bipolar disorder enrolled in the National Institute of Mental Health's Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were assessed for lifetime ADHD. The retrospective course of bipolar disorder, current mood state, and prevalence of other comorbid psychiatric diagnoses were compared for the groups with and without lifetime comorbid ADHD. RESULTS: The overall lifetime prevalence of comorbid ADHD in this large cohort of bipolar patients was 9.5% (95% confidence interval 7.6%-11.4%); 14.7% of male patients and 5.8% of female patients with bipolar disorder had lifetime ADHD. Patients with bipolar disorder and ADHD had the onset of their mood disorder approximately 5 years earlier. After adjusting for age of onset, those with ADHD comorbidity had shorter periods of wellness and were more frequently depressed. We found that patients with bipolar disorder comorbid with ADHD had a greater number of other comorbid psychiatric diagnoses compared with those without comorbid ADHD, with substantially higher rates of several anxiety disorders and alcohol and substance abuse and dependence. CONCLUSIONS: Lifetime ADHD is a frequent comorbid condition in adults with bipolar disorder, associated with a worse course of bipolar disorder and greater burden of other psychiatric comorbid conditions. Studies are needed that focus on the efficacy and safety of treating ADHD comorbid with bipolar disorder.

OBJECTIVE: To examine the potential impact of recovery from substance use disorder (SUD) on the course of bipolar disorder among patients diagnosed with both bipolar and substance use disorders according to DSM-IV criteria. METHOD: As part of the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we examined bipolar disorder status (i.e., whether the patient is recovering or recovered), role functioning, and quality of life in the first 1000 patients to enter the STEP-BD study. We compared patients with no history of SUD, current SUD, and past SUD (i.e., lifetime SUD, but no current SUD) on these parameters. Data were collected between November 1999 and April 2001. RESULTS: A current clinical status of recovering or recovered from bipolar disorder was less likely among patients with current or past SUD compared to patients with no SUD (p < .002). Recovering/recovered status did not differ significantly between patients with current SUD versus past SUD. All 3 groups differed significantly on measures of role functioning as assessed by the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT), with poorest role functioning among patients with current SUD, followed by patients with past SUD (p = .0002). Patients with current or past SUD reported significantly lower quality of life as measured by the LIFE-RIFT and the Quality of Life Enjoyment and Satisfaction Questionnaire and more lifetime suicide attempts (p < .001) than patients without an SUD; patients with past versus current SUD did not differ significantly on these measures. CONCLUSION: The results suggest that patients with bipolar disorder who experience sustained remission from an SUD fare better than patients with current SUD, but not as well as subjects with no history of SUD; differences among the 3 groups appear greatest in the area of role functioning.

Anxiety states and disorders amplify the symptoms and impairment associated with vestibular dysfunction. Five patients with inner ear vestibular dysfunction and anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and received an extensive battery of assessments at baseline and after 12 weeks of treatment. Fluoxetine led to significant or near significant reductions in anxiety measures and in impairment due to dizziness; improvements in clinical balance function and vestibular function were less clear. The data add to the literature suggesting a role for selective serotonin reuptake inhibitors in the treatment of dizziness and anxiety.

BACKGROUND: While the recent loss of a loved one has been identified as a risk factor for suicide in patients with bipolar disorder, and complicated grief (CG) has been associated with elevated rates of suicidality compared with loss without CG, little is known about the frequency or impact of CG in bipolar disorder. We investigated the frequency and implications of loss of loved ones in an ongoing study of bipolar disorder. METHOD: We conducted a survey of 120 patients with well-characterized DSM-IV bipolar disorder participating in Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a large naturalistic study, in order to identify frequency of loss and to examine the presence of CG and its clinical correlates. Survey data were gathered from October 2003 to March 2004. RESULTS: A lifetime history of a significant loss was reported by 86% (103/120) of participants; 24.3% (25/103) of those met criteria for CG, defined as a score > or = 25 on the Inventory of Complicated Grief (ICG), with a mean +/- SD ICG score of 33.7 +/- 6.9. The presence of CG was associated with elevated rates of panic disorder and alcohol abuse comorbidity, as well as other measures of panic symptoms and phobic avoidance. CG was also associated with a higher rate of lifetime suicide attempts, greater functional impairment, and poorer social support. CONCLUSION: Our findings suggest the presence of a substantial burden of comorbid grief-related illness and impairment in patients with bipolar disorder. Further research is needed to understand the overlap of anxiety disorders and phobic avoidance in bipolar patients with complicated grief.