Biomedical subjects

Michael W Otto

Publications and source records attributed to Michael W Otto.

At least 19 recordsLinked to original sources

PubMed2007

Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders.

In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.

Animals↗

PubMed2007

Prediction of "fear" acquisition in healthy control participants in a de novo fear-conditioning paradigm.

Studies using fear-conditioning paradigms have found that anxiety patients are more conditionable than individuals without these disorders, but these effects have been demonstrated inconsistently. It is unclear whether these findings have etiological significance or whether enhanced conditionability is linked only to certain anxiety characteristics. To further examine these issues, the authors assessed the predictive significance of relevant subsyndromal characteristics in 72 healthy adults, including measures of worry, avoidance, anxious mood, depressed mood, and fears of anxiety symptoms (anxiety sensitivity), as well as the dimensions of Neuroticism and Extraversion. Of these variables, the authors found that the combination of higher levels of subsyndromal worry and lower levels of behavioral avoidance predicted heightened conditionability, raising questions about the etiological significance of these variables in the acquisition or maintenance of anxiety disorders. In contrast, the authors found that anxiety sensitivity was more linked to individual differences in orienting response than differences in conditioning per se.

Adult↗

PubMed2006

The association of comorbid anxiety disorders with suicide attempts and suicidal ideation in outpatients with bipolar disorder.

Individuals with bipolar disorder are at increased risk for suicide attempts and completion. Although anxiety may be a modifiable suicide risk factor among bipolar patients, anxiety disorder comorbidity has not been highlighted as critical in identification of high-risk individuals nor has its treatment been integrated into suicide prevention strategies. In this study, ancillary to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 120 outpatients with bipolar disorder completed detailed assessment of suicidal ideation and behaviors. We examined the association of current and lifetime comorbid anxiety disorders with suicidal ideation and behaviors univariately and with adjustment for potential confounders in regression models. Lifetime anxiety disorders were associated with a more than doubling of the odds of a past suicide attempt, and current anxiety comorbidity was associated with a more than doubling of the odds of current suicidal ideation. Individuals with current anxiety disorders had more severe suicidal ideation, a greater belief suicide would provide relief, and a higher expectancy of future suicidal behaviors. However, some of these associations appeared to be better accounted for by measures of bipolar severity including an earlier age at bipolar onset and a lack of current bipolar recovery. Comorbid anxiety disorders may play a role in characteristics of bipolar disorder that then elevate risk for suicidal ideation and attempts. While further research is needed to establish the precise nature of these associations, our data support that the presence of comorbid anxiety disorders in individuals with bipolar disorder should trigger careful clinical assessment of suicide risk.

Adult↗

PubMed2006

Understanding the link between anxiety symptoms and suicidal ideation and behaviors in outpatients with bipolar disorder.

BACKGROUND: Prior studies suggest an association between anxiety comorbidity and suicidal ideation and behaviors in bipolar disorder. However, the nature of this association remains unclear. METHODS: We examined a range of anxiety symptoms, including panic, phobic avoidance, anxiety sensitivity, worry and fear of negative evaluation, in 98 patients with bipolar disorder. We predicted that each anxiety dimension would be linked to greater suicidal ideation and behavior as measured by Linehan's Suicide Behaviors Questionnaire (SBQ), greater depressive rumination, and poorer emotional processing and expression. RESULTS: Each anxiety dimension except fear of negative evaluation was associated with greater SBQ score, greater rumination, and lower levels of emotional processing in univariate analyses. Depressive rumination was a significant predictor of higher SBQ scores in a stepwise multivariate model controlling for age, gender, bipolar subtype, and bipolar recovery status; the association between the anxiety symptom dimensions and SBQ score was found to be redundant with depressive rumination. Emotional processing emerged as protective against suicidal ideation and behaviors in men only, while emotional expression was a significant predictor of lower SBQ scores for women and for the full sample; however, emotional expression was not significantly correlated with anxiety symptoms. Confirmatory analyses examining only those in recovery or recovered (n=68) indicated that the link between rumination and suicidality was not explained by depression. LIMITATIONS: Interpretation is limited by the cross-sectional study design. CONCLUSIONS: These findings indicate that increased ruminations may mediate the association between anxiety and suicidal ideation/behavior. In men, lower emotional processing may also play a role in this relationship.

Adaptation, Psychological↗

PubMed2006

Prevention of missing data in clinical research studies.

Missing data is a problem that is ubiquitous to all clinical studies and a source of multiple problems from an analytic point of view (reduced statistical power, increased the type I error, bias) Statistical approaches have been developed to analyze data collected from trials with missing data. Understanding and implementing the appropriate statistical technique is essential but should be differentiated from preventive approaches that are designed to reduce rates of missing data In this article, we draw attention to these preventive efforts. Seven steps to minimizing the amount of missing data are defined as documentation, training, monitoring reports, patient contact, data entry and management, pilot studies, and communication. Although the implementation of these approaches is time consuming and costly, the overall quality of the study is increased. Despite efforts devoted to areas, no study is without missing data. Once the study is completed, it is essential to assess the pattern of missing data and apply the appropriate statistical analysis.

Bias↗

PubMed2006

Augmentation of exposure therapy with D-cycloserine for social anxiety disorder.

CONTEXT: Social anxiety disorder (SAD) is common and debilitating. Although exposure therapy is one of the most effective forms of psychotherapy for this disorder, many patients remain symptomatic. Fear reduction in exposure therapy is similar to extinction learning, and early clinical data with specific phobias suggest that the treatment effects of exposure therapy for SAD may be enhanced with d-cycloserine, an agonist at the glutamatergic N-methyl-d-aspartate receptor. OBJECTIVE: To determine whether short-term treatment with 50 mg of d-cycloserine enhances the efficacy of exposure therapy for SAD. DESIGN: Randomized, double-blind, placebo-controlled augmentation trial examining the combination of d-cycloserine or pill placebo with exposure therapy for SAD. SETTING: Patients were self-referred from the general community to 1 of 3 research clinics. PARTICIPANTS: Twenty-seven participants meeting DSM-IV criteria for SAD with significant public speaking anxiety. INTERVENTIONS: Following a diagnostic interview and pretreatment assessment, participants received 5 therapy sessions delivered in either an individual or group therapy format. The first session provided an introduction to the treatment model and was followed by 4 sessions emphasizing exposure to increasingly challenging public speech situations with videotaped feedback of performances. One hour prior to each session, participants received single doses of d-cycloserine or placebo. MAIN OUTCOME MEASURES: Symptoms were assessed by patient self-report and by clinicians blind to the randomization condition before treatment, after treatment, and 1 month after the last session. RESULTS: Participants receiving d-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range. CONCLUSION: The pilot data provide preliminary support for the use of short-term dosing of d-cycloserine as an adjunctive intervention to exposure therapy for SAD.

Adult↗

PubMed2006

Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles.

CONTEXT: Transition to menopause has long been considered a period of increased risk for depressive symptoms. However, it is unclear whether this period is one of increased risk for major depressive disorder, particularly for women who have not had a previous episode of depression. OBJECTIVE: To examine the association between the menopausal transition and onset of first lifetime episode of depression among women with no history of mood disturbance. DESIGN: Longitudinal, prospective cohort study. SETTING: A population-based cross-sectional sample. PARTICIPANTS: Premenopausal women, 36 to 45 years of age, with no lifetime diagnosis of major depression (N = 460), residing in 7 Boston, Mass, metropolitan area communities. Main Outcome Measure Incidence of new onset of depression based on structured clinical interviews, Center for Epidemiologic Studies Depression Scale scores, and an operational construct for depression. RESULTS: Premenopausal women with no lifetime history of major depression who entered the perimenopause were twice as likely to develop significant depressive symptoms as women who remained premenopausal, after adjustment for age at study enrollment and history of negative life events. The increased risk for depression was somewhat greater in women with self-reported vasomotor symptoms. CONCLUSIONS: The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness.

Adult↗

PubMed2006

Do baseline client characteristics predict the therapeutic alliance in the treatment of schizophrenia?

This study examined clinical predictors of client and therapist alliance ratings early in therapy, the relationship between client and therapist alliance ratings, and the psychometric properties of the Working Alliance Inventory in individuals with schizophrenia receiving manual-based treatment. Assessment of clinical symptoms and social functioning were conducted at baseline, and alliance ratings were obtained at 5 weeks. The Working Alliance Inventory had high internal consistency, but there were low correlations between client and therapist ratings. Results also indicated that social functioning and the activation and autistic preoccupation factors on the Positive and Negative Syndrome Scale were significant predictors of therapists' alliance ratings. There were no significant relationships between clinical predictors and clients' therapeutic alliance ratings. The findings indicate that client interpersonal factors are significant predictors of the therapist-rated alliance in the treatment of schizophrenia. Low correlations between clients' and therapists' ratings of the alliance should be examined in future research.

Adult↗

PubMed2006

The relationship of anxiety disorders, anxiety sensitivity and pulmonary dysfunction with dyspnea-related distress and avoidance.

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.

Anxiety Disorders↗

PubMed2006

Prospective predictors of suicide and suicide attempts in 1,556 patients with bipolar disorders followed for up to 2 years.

OBJECTIVES: Bipolar disorders are associated with high rates of suicide attempts (SAs) and completions. Several factors have been reported to be associated with suicide in persons with bipolar disorder, but most studies to date have been retrospective and have not utilized multivariate statistics to account for the redundant prediction among variables submitted for analysis. METHODS: This study examined the association between baseline clinical and demographic variables and subsequent SAs and completions through 2 years of follow-up of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern-mixture model. RESULTS: Of the sample with complete data (n = 1,556), 57 patients (3.66%) experienced an SA or completion (CS). Several variables predicted suicidality (SA + CS) in this data set when considered alone, but after controlling for redundant prediction from other baseline characteristics, only history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days depressed in the past year (OR = 1.16, p = 0.036) were significantly associated with SAs and completions. A secondary analysis included a greater number of variables but a smaller sample size (n = 1,014). In the secondary analyses, only prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). CONCLUSIONS: These results indicate that patients with bipolar disorder who present with a history of SAs are over four times as likely to have a subsequent SA or completion. Further studies are needed to evaluate and prevent future attempts in this high-risk cohort.

Adolescent↗

PubMed2006

Quality of life and treatment outcome in panic disorder: cognitive behavior group therapy effects in patients refractory to medication treatment.

BACKGROUND: Improvements in quality of life (QoL) as well as symptomatic relief are important outcomes for the treatment of panic disorder (PD). The aim of this study is to assess the impact of brief cognitive behavior group therapy (CBGT) for panic disorder on QoL and to identify the clinical features associated with these changes. METHODS: Thirty-six patients with PD refractory to pharmacological treatment took part in a treatment protocol consisting of 12 sessions of CBGT. To evaluate the changes in QoL, the WHOQOL-bref was administered before and after treatment. RESULTS: Thirty-two patients completed the treatment. Significant improvement in all domains of QoL was observed (p< 0.001), which was associated with reductions in general and anticipatory anxiety (p = 0.018) and agoraphobic avoidance (p = 0.046). Consistent with previous findings, associations between QoL and panic-free status did not reach significance in this small study (p = 0.094). CONCLUSIONS: CBGT was efficacious in the treatment of PD; the symptoms of anticipatory anxiety and avoidance appear to be more important than episodic panic episodes in affecting QoL.

Adult↗

PubMed2006

Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE: Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence. METHOD: The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression. RESULTS: Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence. CONCLUSIONS: Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence.

Adolescent↗

PubMed2006

Psychotherapy, symptom outcomes, and role functioning over one year among patients with bipolar disorder.

OBJECTIVE: Randomized trials indicate that psychosocial interventions effective adjuncts to pharmacotherapy in bipolar disorder (1,2). A one-year naturalistic-prospective design was used to examine the association between psychotherapy use and the symptomatic and functional outcomes of patients with bipolar disorder. METHODS: Patients with bipolar disorder in a depressed phase (N=248) were drawn from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic Treatment Enhancement Program (STEP-BD), a study of patients with bipolar disorder receiving best-practice pharmacotherapy. Patients were seen clinics and interviewed every three months over one year regarding of psychotherapy services, symptoms, and role functioning. Mixed-effects regression models were used to examine whether the amount of psychotherapy the patients received during each three-month interval was associated with symptomatic or psychosocial functioning during the same or a subsequent three-month interval. RESULTS: During the study year, percent of the patients had at least one psychotherapy session. Among patients who began an interval with severe depressive symptoms or low functioning, having more frequent sessions of psychotherapy was associated with less severe mood symptoms and better functioning in the same or a subsequent study interval. In contrast, among patients who began interval with less severe depressive symptoms or higher functioning, fewer psychotherapy sessions were associated with less severe depressive symptoms and greater functioning in the same or a subsequent interval. CONCLUSIONS: Intensive psychotherapy may be most applicable to severely ill patients with bipolar disorder, whereas briefer treatments may be adequate for less severely ill patients.

Activities of Daily Living↗

PubMed2006

Persistent posttraumatic stress disorder following September 11 in patients with bipolar disorder.

OBJECTIVE: We examined the development of posttraumatic stress disorder (PTSD) following indirect exposure to the September 11, 2001, terrorist attacks in a cohort at high risk for adverse trauma-related sequelae as a result of having bipolar disorder. METHOD: Subjects (N = 137) were participants in the ongoing, naturalistic, longitudinal study Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) prior to September 11, 2001. The present study examined prospectively collected pre-event information about bipolar disorder and other potential predictors of PTSD, along with assessment of the level of indirect trauma exposure (i.e., via media) and peritraumatic distress in the aftermath of September 11, and their association with 9/11-related, new-onset PTSD as assessed by a self-report measure, the Posttraumatic Stress Diagnostic Scale. RESULTS: Posttrauma assessments were completed a mean +/- SD of 430.6 +/- 78.7 days (range, 0.5-1.5 years) after September 11. Twenty percent (N = 27) of patients reported development of new-onset PTSD in response to the September 11 attacks. Rates of PTSD were significantly associated with the presence of a hypomanic, manic, or mixed mood state at the time of trauma (chi(2) = 4.25; p < .05); 62% of patients in these states developed PTSD. Mania/hypomania remained a significant predictor of PTSD in response to the September 11 attacks after controlling for peritraumatic exposure and distress variables, suggestive of a substantial increase in risk compared with those in recovery (OR = 17; 95% CI = 2.6 to 115.6; p = .0034). CONCLUSIONS: Rates of persistent new-onset PTSD among bipolar patients were elevated in the aftermath of the September 11 attacks. Our findings suggest that the presence of a manic state may be the most critical risk factor for adverse sequelae following indirect traumatic exposure in bipolar individuals.

Adult↗

PubMed2005

Anxiety disorders among patients with co-occurring bipolar and substance use disorders.

Bipolar and substance use disorders are known to co-occur frequently, but limited attention has been paid to anxiety disorders that may accompany this dual diagnosis. Therefore, we examined the prevalence and nature of anxiety disorders among treatment-seeking patients diagnosed with current bipolar and substance use disorders, and investigated the association between anxiety disorders and substance use. Among 90 participants diagnosed with bipolar disorder I (n = 75, 78%) or II (n = 15, 22%), 43 (48%) had a lifetime anxiety disorder, with post-traumatic stress disorder (PTSD) occurring most frequently (n = 21, 23%). We found that those with PTSD, but not with the other anxiety disorders assessed, began using drugs at an earlier age and had more lifetime substance use disorders, particularly cocaine and amphetamine use disorders, than those without PTSD. Further examination revealed that (1) most participants with PTSD were women, (2) sexual abuse was the most frequently reported index trauma, and (3) the mean age of the earliest index trauma occurred before the mean age of initiation of drug use. Our findings point to the importance of further investigating the ramifications of a trauma history among those who are dually diagnosed with bipolar and substance use disorders.

Adult↗

PubMed2005

Perceived criticism from family members as a predictor of the one-year course of bipolar disorder.

Few studies have examined the prognostic value of family factors in the course of bipolar affective disorder. The current study examined a self-report measure of expressed emotion as a predictor of the 1-year course of the illness. Patients with bipolar disorder (N=360) filled out the four-item Perceived Criticism Scale concerning one or more relatives or close friends. Independent evaluators followed patients over 1 year and rated them on measures of depressive and manic symptoms and the percentage of days in recovery status. Patients' ratings of the severity of criticisms from relatives did not predict patients' mood disorder symptoms at follow-up. However, patients who were more distressed by their relatives' criticisms had more severe depressive and manic symptoms and proportionately fewer days well during the study year than patients who were less distressed by criticisms. Patients who reported that their relatives became more upset by the patients' criticisms had less severe depressive symptoms at follow-up. Results indicate that a brief rating of subjective distress in response to familial criticism is a useful prognostic device and may aid in planning psychosocial interventions for patients with bipolar disorder.

Adult↗

PubMed2005

Rates of isolated sleep paralysis in outpatients with anxiety disorders.

Initial research suggests that rates of isolated sleep paralysis (ISP) are elevated in individuals with panic disorder and particularly low in individuals with other anxiety disorders. To further evaluate these findings, we examined rates of ISP in a sample outpatients with primary diagnoses of panic disorder (n=24), social anxiety disorder (n=18), or generalized anxiety disorder (n=18). We obtained an overall rate of ISP of 19.7%; rates for patients with panic disorder (20.8%) fell between those with generalized anxiety disorder (15.8%) and social phobia (22.2%). Analysis of comorbidities failed to provide evidence of link between depressive disorders and ISP, but did indicate a significant association between anxiety comorbidity and higher rates of ISP. Results are discussed relative to other variables predicting variability in the occurrence of ISP.

Adult↗

PubMed2005

One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission.

Non-response to pharmacotherapy for panic disorder (PD) is a well-documented problem. However, little information exists to guide next-step strategies for these non-responders. In addition to pharmacologic augmentation strategies, several studies support the efficacy of cognitive-behavior therapy (CBT) for these patients, although data on long-term outcomes has been lacking. In this study, we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy. Sustained significant benefit was found for all dimensional outcome scores, and nearly two-thirds of the sample met remission criteria. This occurred with reductions in medication use over the follow-up period. Negative predictors of remission status included comorbid dysthymia, social phobia, and generalized anxiety disorder. These results provide additional evidence for the efficacy of CBT for medication non-responders with PD.

Adult↗