Enhancing outcomes in patients with bipolar disorder: results from the Bipolar Disorder Center for Pennsylvanians Study.

INTRODUCTION: We developed models of Specialized Care for Bipolar Disorder (SCBD) and a psychosocial treatment [Enhanced Clinical Intervention (ECI)] that is delivered in combination with SCBD. We investigated whether SCBD and ECI + SCBD are able to improve outcomes and reduce health disparities for young and elderly individuals, African Americans, and rural residents with bipolar disorder. METHOD: Subjects were 463 individuals with bipolar disorder, type I, II, or not otherwise specified, or schizoaffective disorder, bipolar type, randomly assigned to SCBD or ECI + SCBD and followed longitudinally for a period of one to three years at four clinical sites. RESULTS: Both treatment groups significantly improved over time, with no significant differences based on age, race, or place of residence, except for significantly greater improvement among elderly versus adult subjects. Improvement in quality of life was greater in the ECI + SCBD group. Of the 299 participants who were symptomatic at study entry, 213 achieved recovery within 24 months, during which 86 of the 213 subjects developed a new episode. No significant difference was found for race, place of residence, or age between the participants who experienced a recurrence and those who did not. However, the adolescent patients were less likely than the adult and elderly patients to experience a recurrence. CONCLUSION: This study demonstrated the effectiveness of SCBD and the additional benefit of ECI independent of age, race, or place of residence. It also demonstrated that new mood episodes are frequent in individuals with bipolar disorder who achieve recovery and are likely to occur in spite of specialized, guideline-based treatments.

The Career Development Institute for Psychiatry: an innovative, longitudinal program for physician-scientists.

OBJECTIVES: The Research Career Development Institute for Psychiatry is a collaboration between the University of Pittsburgh and Stanford University to recruit and train a broad-based group of promising junior physicians by providing the necessary skills and support for successful research careers in academic psychiatry. METHODS: Participants whose interests span the spectrum of clinical and intervention research attend a multiday career development institute workshop and follow-up annual booster sessions conducted with the American College of Neuropsychopharmacology. The program identifies and trains 20 new physician-researchers each year, with particular emphasis on women, minorities, and those from less research-intensive psychiatry departments, and provides booster sessions for all trainees. An annual evaluation is used to renew and update the content of the institutes and to measure the long-term value in research and career success. RESULTS: This report is based on the results of 77 participants from the first four Career Development Institute classes. Qualitative assessment of the program content and process led to improvements in each successive year's workshop. Preliminary quantitative follow-up assessment of participants indicated successful career progress toward individual objectives. CONCLUSION: By providing early career investigators with skills to cope with local and national forces in academic medical centers, the Career Development Institute is significantly contributing to the development of the next generation of leading academic clinical researchers in mental health and can serve as a model for other biomedical research arenas.

Using computerized adaptive testing to reduce the burden of mental health assessment.

OBJECTIVE: This study investigated the combination of item response theory and computerized adaptive testing (CAT) for psychiatric measurement as a means of reducing the burden of research and clinical assessments. METHODS: Data were from 800 participants in outpatient treatment for a mood or anxiety disorder; they completed 616 items of the 626-item Mood and Anxiety Spectrum Scales (MASS) at two times. The first administration was used to design and evaluate a CAT version of the MASS by using post hoc simulation. The second confirmed the functioning of CAT in live testing. RESULTS: Tests of competing models based on item response theory supported the scale's bifactor structure, consisting of a primary dimension and four group factors (mood, panic-agoraphobia, obsessive-compulsive, and social phobia). Both simulated and live CAT showed a 95% average reduction (585 items) in items administered (24 and 30 items, respectively) compared with administration of the full MASS. The correlation between scores on the full MASS and the CAT version was .93. For the mood disorder subscale, differences in scores between two groups of depressed patients--one with bipolar disorder and one without--on the full scale and on the CAT showed effect sizes of .63 (p<.003) and 1.19 (p<.001) standard deviation units, respectively, indicating better discriminant validity for CAT. CONCLUSIONS: Instead of using small fixed-length tests, clinicians can create item banks with a large item pool, and a small set of the items most relevant for a given individual can be administered with no loss of information, yielding a dramatic reduction in administration time and patient and clinician burden.

Randomized trial of weekly, twice-monthly, and monthly interpersonal psychotherapy as maintenance treatment for women with recurrent depression.

OBJECTIVE: The authors sought to determine whether a greater frequency of interpersonal psychotherapy (IPT) sessions during maintenance treatment has a greater prophylactic effect than a previously validated once-a-month treatment. METHOD: A total of 233 women 20-60 years of age with recurrent unipolar depression were treated in an outpatient research clinic. After participants had achieved remission with weekly IPT or, if required, with weekly IPT plus antidepressant pharmacotherapy, they were randomly assigned to weekly, twice-monthly, or monthly maintenance IPT monotherapy for 2 years or until a recurrence of their depression occurred. RESULTS: Among participants who remitted with IPT alone and entered maintenance treatment (N=99), 19 (26%) of the 74 who remained in the study throughout the 2-year maintenance phase experienced a recurrence of depression. Among participants who required the addition of a selective serotonin reuptake inhibitor to achieve remission (N=90), 32 (36%) sustained that remission through continuation treatment and drug discontinuation and began maintenance treatment; of these, 13 (50%) of the 26 who remained in the study throughout the maintenance phase experienced a recurrence. Survival analysis of time to recurrence by randomized treatment frequency showed no effect on recurrence-free survival in either treatment subgroup. CONCLUSIONS: These results suggest that maintenance IPT, even at a frequency of only one visit per month, is a good method of prophylaxis for women who can achieve remission with IPT alone. In contrast, among those who require the addition of pharmacotherapy, IPT monotherapy represents a significantly less efficacious approach to maintenance treatment.

Clinical significance of lifetime panic spectrum symptoms in the treatment of patients with bipolar I disorder.

BACKGROUND: Given the observed association between panic disorder and bipolar disorder and the potential negative influence of panic symptoms on the course of bipolar illness, we were interested in the effects of what we have defined as "panic spectrum" conditions on the clinical course and treatment outcome in patients with bipolar I (BPI) disorder. We hypothesized that lifetime panic spectrum features would be associated with higher levels of suicidal ideation and a poorer response to acute treatment of the index mood episode in this patient population. METHODS: A sample of 66 patients with BPI disorder completed a self-report measure of lifetime panic-agoraphobic spectrum symptoms. Patients falling above and below a predefined clinical threshold for panic spectrum were compared for clinical characteristics, the presence of suicidal ideation during acute treatment, and acute treatment response. RESULTS: Half of this outpatient sample reported panic spectrum features above the predefined threshold. These lifetime features were associated with more prior depressive episodes, higher levels of depressive symptoms, and greater suicidal ideation during the acute-treatment phase. Patients with BPI disorder who reported high lifetime panic-agoraphobic spectrum symptom scores took 27 weeks longer than those who reported low scores to remit with acute treatment (44 vs 17 weeks, respectively). CONCLUSIONS: The presence of lifetime panic spectrum symptoms in this sample of patients with BPI disorder was associated with greater levels of depression, more suicidal ideation, and a marked (6-month) delay in time to remission with acute treatment. Alternate treatment strategies are needed for patients with BPI disorder who endorse lifetime panic spectrum features.

Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry.

OBJECTIVE: Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959. METHOD: Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. CONCLUSIONS: Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment.

Demographic and clinical characteristics of individuals in a bipolar disorder case registry.

BACKGROUND: The goal of this analysis was to characterize a cohort of 3000 persons who self-identified as having bipolar disorder by demographic, clinical, and treatment characteristics and to document the burden that this disorder imposed on their lives. METHOD: The Stanley Center Bipolar Disorder Registry used a variety of recruitment methods to reach people with bipolar disorder. The cohort included those currently in treatment and those active in support groups. Registrants completed an interviewer-administered questionnaire to obtain information on demographic characteristics, clinical history, and treatment history. RESULTS: The median age of the 2839 patients who were analyzed was 40.1 years, 64.5% were women, and over 90% were white. The median age at onset was 17.5 years, and the mean was 19.8 years. Despite the fact that over 60% completed at least some college and 30% completed college, 64% were currently unemployed. The patients' family histories point to a high prevalence of mental disorder in the families, especially mood disorders. Patients were concurrently taking multiple medications, and more than one third were taking at least 3 types of psychotropic medications. This pattern of pharmacotherapy was consistent with participants' overall mood ratings, which demonstrated how unusual it was for them to be symptom-free over a 6-month period. CONCLUSION: Our present findings point to the chronicity and severity of bipolar disorder as experienced in the community. We still need to develop better interventions, ensure access to care consistent with current consensus guidelines, and initiate care as early as possible in the course of the condition.

Adult separation anxiety: psychometric properties of a new structured clinical interview.

Separation anxiety has traditionally been characterized and assessed as a disorder that is unique to childhood. Yet the core symptoms of separation anxiety, i.e. excessive and often disabling distress when faced with actual or perceived separation from major attachment figures, may persist or even arise during adulthood. We report on the psychometric properties of a new structured clinical interview designed to assess symptoms of separation anxiety as experienced both during childhood and adulthood. This instrument, called the Structured Clinical Interview for Separation Anxiety Symptoms (or SCI-SAS), was administered as part of an assessment battery to 91 adult psychiatric outpatients and 20 non-psychiatric controls. Results indicate that this instrument displays excellent psychometric properties, including good internal consistency, a clear factor structure, and exceptional levels of convergent and discriminate validity. These results highlight the feasibility and potential clinical utility of assessing age-appropriate symptoms of separation anxiety experienced during adulthood.

Microstructure of sleep in depressed patients according to the cyclic alternating pattern.

BACKGROUND: The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS: 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS: A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION: In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Bipolar disorder center for Pennsylvanians: implementing an effectiveness trial to improve treatment for at-risk patients.

OBJECTIVE: Adolescents, elderly persons, African Americans, and rural residents with bipolar disorder are less likely than their middle-aged, white, urban counterparts to be diagnosed, receive adequate treatment, remain in treatment once identified, and have positive outcomes. The Bipolar Disorder Center for Pennsylvanians (BDCP) study was designed to address these disparities. This report highlights the methods used to recruit, screen, and enroll a cohort of difficult-to-recruit individuals with bipolar disorder. METHODS: Study sites included three specialty clinics for bipolar disorder in a university setting and a rural behavioral health clinic. Study operations were standardized, and all study personnel were trained in study procedures. Several strategies were used for recruitment. RESULTS: It was possible to introduce the identical assessment and screening protocol in settings regardless of whether they had a history of implementing research protocols. This protocol was also able to be used across the age spectrum, in urban and rural areas, and in a racially diverse cohort of participants. Across the four sites 515 individuals with bipolar disorder were enrolled as a result of these methods (69 African Americans and 446 non-African Americans). Although clinical characteristics at study entry did not differ appreciably between African Americans and non-African Americans, the pathways into treatment differed significantly. CONCLUSIONS: Rigorous recruitment and assessment procedures can be successfully introduced in different settings and with different patient cohorts, thus facilitating access to high-quality treatment for individuals who frequently do not receive appropriate care for bipolar disorder.

The role of interpersonal and social rhythm therapy in improving occupational functioning in patients with bipolar I disorder.

OBJECTIVE: Recent studies demonstrate the poor psychosocial outcomes associated with bipolar disorder. Occupational functioning, a key indicator of psychosocial disability, is often severely affected by the disorder. The authors describe the effect of acute treatment with interpersonal and social rhythm therapy on occupational functioning over a period of approximately 2.5 years. METHOD: Patients with bipolar I disorder were randomly assigned to receive either acute and maintenance interpersonal and social rhythm therapy, acute and maintenance intensive clinical management, acute interpersonal and social rhythm therapy and maintenance intensive clinical management, or acute intensive clinical management and maintenance interpersonal and social rhythm therapy, all with appropriate pharmacotherapy. Occupational functioning was measured with the UCLA Social Attainment Scale at baseline, at the end of acute treatment, and after 1 and 2 years of maintenance treatment. RESULTS: The main effect of treatment did not reach conventional levels of statistical significance; however, the authors observed a significant time by initial treatment interaction. Participants initially assigned to interpersonal and social rhythm therapy showed more rapid improvement in occupational functioning than those initially assigned to intensive clinical management, primarily accounted for by greater improvement in occupational functioning during the acute treatment phase. At the end of 2 years of maintenance treatment, there were no differences between the treatment groups. A gender effect was also observed, with women who initially received interpersonal and social rhythm therapy showing more marked and rapid improvement. There was no effect of maintenance treatment assignment on occupational functioning outcomes. CONCLUSIONS: In this study, interpersonal and social rhythm therapy, with its emphasis on amelioration of interpersonal and role functioning, improved occupational functioning significantly more rapidly than did a psychoeducational and supportive approach with no such emphasis on functional capacities.

Addressing the challenges of a cross-national investigation: lessons from the Pittsburgh-Pisa study of treatment-relevant phenotypes of unipolar depression.

BACKGROUND: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. PURPOSE: This report describes how those challenges were met in the study "Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy. METHODS: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems. RESULTS: By having bilingual investigators and staff members who spent time at one another's sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year. LIMITATIONS: This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings. CONCLUSIONS: The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them.

African-American participants in a bipolar disorder registry: clinical and treatment characteristics.

OBJECTIVES: The goal of this paper was to compare clinical characteristics and treatment history of African-American and Caucasian participants in a bipolar disorder registry. METHODS: The Western Pennsylvania Bipolar Disorder Registry used several recruitment methods to reach individuals self-identified as having bipolar disorder. Individuals who contacted and joined the registry completed an interviewer-administered questionnaire on clinical characteristics and treatment history. A sample of 2,718 registry participants was analyzed in order to compare these characteristics and history by race. RESULTS: African-Americans in the registry reported a greater number of inpatient hospitalizations (9.8 versus 4.4) than Caucasians, as well as a higher suicide attempt rate (64% versus 49%). African-American participants were more likely to report a family member with schizophrenia. With respect to psychotropic medication, African-Americans were less likely to report taking antimanic medication or benzodiazepines, but more likely to report taking antipsychotics than Caucasians. CONCLUSIONS: The present findings reinforce previous reports regarding the chronicity and severity of bipolar disorder among African-Americans. They also support previous studies that found high rates of attempted suicide among African-Americans with bipolar disorder. These findings provide further impetus for specific community and mental health services delivery efforts to reduce barriers to early accurate diagnosis and to appropriate ambulatory treatment for bipolar disorder.

Measuring social anxiety and obsessive-compulsive spectra: comparison of interviews and self-report instruments.

The present report analyzes the agreement between the interview and the self-report formats of the instruments Structured Clinical Interview for Social Anxiety Spectrum (SCI-SHY) and Structured Clinical Interview for Obsessive Compulsive Spectrum (SCI-OBS), already validated, in three psychiatric patient samples and controls. Thirty patients (10 with obsessive-compulsive disorder [OCD], 10 with social anxiety disorder [SAD], 10 with recurrent unipolar depression in remission) and 20 control subjects (10 university students, 10 ophthalmologic patients) were assessed using the SCI-SHY, the SCI-OBS, and the self report version of the two instruments. Agreement between the two versions was very good for the seven SCI-OBS domains (with intraclass correlation coefficients [ICCs] ranging from 0.80 to 0.96) and the four SCI-SHY domains (ICCs from 0.74 to 0.90). When items were analyzed individually, subjects tended to under-report some phobia-related problems in the interview. The total number of items endorsed in the SCI-SHY, but not in the SCI-OBS, was affected by the order of administration: when the SCI-SHY interview was administered first, subjects reported a median of five more symptoms; when the self-report was administered first, there was no significant difference in the number of symptoms endorsed in the two formats. However, this difference is not clinically important, given the large number of items comprising the instruments, and might be explained by the fact that subjects are likely to overemphasize occasional symptoms or behaviors when they are asked by the interviewer to answer a long series of "new" questions as accurately as possible. Given the high agreement between domain scores in the two formats of the instruments and the fact that scores are virtually identical when the self-report is administered first, we recommend the use of the self-report versions in clinical and research settings.

Development and preliminary testing of the General 5-Spectrum Measure (GSM-V).

The Collaborative Spectrum Project has developed structured interviews and self-report instruments to assess the spectrum of symptomatology related to panic-agoraphobia, mood, social phobia, and obsessive-compulsive and eating disorders. In order to obtain a rapid pre-test on all five of these spectrum conditions, the authors sought to develop a brief instrument that would tap these conditions. This paper reports on 1) the procedures to derive this composite instrument, the General 5-Spectrum Measure (GSM-V), by selecting items from five existing spectrum instruments, and 2) preliminary testing of the internal consistency and test-retest reliability of the GSM-V. The GSM-V consists of 54 items grouped into scales that explore the five spectra described above. It was derived from existing data on five Structured Clinical Interviews that were designed to assess spectrum features by using multiple regression models. The GSM-V was administered as a stand-alone instrument along with the self-report versions of the spectrum interviews to a sample of 56 psychiatric patients in order to determine the internal consistency of its scales and the correlation with the parent spectrum measures. Moreover, to determine whether subjects would respond consistently to the same items on two different occasions (test-retest reliability), the GSM-V was re-administered within 1 month from the baseline. From each of the five spectrum interviews, items were selected that accounted for a significant proportion of variance of the total score of the parent instrument. The five sets of items so selected constitute separate scales. The scales of the GSM-V had a good to excellent internal consistency, excellent test-retest reliability, and proved to reproduce adequately the long-form measures. The GSM-V appears to provide a reliable alternative to the five longer spectrum interviews. It is envisaged that the instrument will be most useful as a pre-test to identify subjects with spectrum features that should be explored in greater detail. Additionally, it could provide a better characterization of patients with a syndromal level Axis-I disorder, who might require specific treatment strategies targeted to co-occurring subsyndromal conditions.

Measuring mood spectrum: comparison of interview (SCI-MOODS) and self-report (MOODS-SR) instruments.

Spectrum phenomena include, in addition to the typical DSM core symptoms, isolated or atypical symptoms, often of low severity, as well as trait-like behavioral features that arise as a result of coping with the psychopathology. We have demonstrated the psychometric properties of five Structured Clinical Interviews for the assessment of specific mood and anxiety spectrum conditions, including the Structured Clinical Interview for Mood Spectrum (SCI-MOODS). The present report describes the reliability of the self-report version (MOODS-SR) of the SCI-MOODS in a sample of 21 patients with a mood disorder and 20 control subjects. Agreement between the self-report and the interview formats was substantial. Intraclass correlation coefficients (ICC) ranged from 0.88 to 0.97. Our findings provide support for the reliability of the MOODS-SR questionnaire.