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Original Article |

Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative FREE

Kathleen R. Merikangas, PhD; Robert Jin, MA; Jian-Ping He, MD; Ronald C. Kessler, PhD; Sing Lee, MB, BS, FRCPsych; Nancy A. Sampson, BA; Maria Carmen Viana, MD, PhD; Laura Helena Andrade, MD, PhD; Chiyi Hu, MD, PhD; Elie G. Karam, MD; Maria Ladea, MD, PhD; Maria Elena Medina-Mora, PhD; Yutaka Ono, MD; Jose Posada-Villa, MD; Rajesh Sagar, MD; J. Elisabeth Wells, PhD; Zahari Zarkov, MD
[+] Author Affiliations

Author Affiliations: National Institute of Mental Health, Bethesda, Maryland (Drs Merikangas and He); Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts (Mr Jin, Dr Kessler, and Ms Sampson); Department of Psychiatry; The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (Dr Lee) and Shenzhen Institute of Mental Health and Shenzhen Kangning Hospital, Shenzhen (Dr Hu), People's Republic of China; Section of Psychiatric Epidemiology (Drs Viana and Andrade) and Laboratory of Medical Investigation 23 (Dr Andrade), Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil; St George Hospital University Medical Center, Balamand University, Faculty of Medicine, Institute for Development, Research, Advocacy and Applied Care, Medical Institute for Neuropsychological Disorders, Beirut, Lebanon (Dr Karam); Department of Psychiatry, University of Medicine and Pharmacy “Carol Davila,” Bucharest, Romania (Dr Ladea); National Institute of Psychiatry, Mexico City, Mexico (Dr Medina-Mora); Health Center, Keio University, Yokohama, Japan (Dr Ono); Colegio Mayor de Cundinamarca University, Bogota, Colombia (Dr Posada-Villa); Department of Psychiatry, All India Institute of Medical Sciences, Delhi, India (Dr Sagar); Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand (Dr Wells); and National Center of Public Health Protection, Directorate Mental Health, Sofia, Bulgaria (Dr Zarkov).


Arch Gen Psychiatry. 2011;68(3):241-251. doi:10.1001/archgenpsychiatry.2011.12.
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Context  There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods.

Objectives  To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative.

Design, Setting, and Participants  Cross-sectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview.

Main Outcome Measures  Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment.

Results  The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system.

Conclusions  Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.

Figures in this Article

Bipolar disorder (BP) is responsible for the loss of more disability-adjusted life-years than all forms of cancer or major neurologic conditions such as epilepsy and Alzheimer disease,1 primarily because of its early onset and chronicity across the life span. Aggregate estimates of the prevalence of BP indicate that approximately 1.0% of the general population meet lifetime criteria for BP type I (BP-I).27 Estimates of the lifetime prevalence of BP-II have been provided by only 1 investigation, which reported a median lifetime prevalence of 1.2%.3 A recent international review8 of both DSM-IV BP-I and BP-II in population studies yielded an aggregate cross-study lifetime prevalence estimate of 1.2%, ranging from 0.1% in Nigeria9 to 3.3% in the United States.10

Divergence in cross-country prevalence rates4 may reflect methodologic differences in diagnostic procedures or assessment methods as well as true differences in disease prevalence. As highlighted by the classic US-UK study that demonstrated that differential diagnostic practices primarily explained the wide divergence in rates of schizophrenia and manic depressive psychosis in the United States and United Kingdom,1113 the application of standardized diagnostic criteria for mental disorders has facilitated international comparisons. Likewise, the development of common diagnostic assessment methods such as the Composite International Diagnostic Interview (CIDI)14 has also reduced methodologic sources of variation in international prevalence estimates.

In addition to the need for common methods, converging evidence from clinical and epidemiologic studies suggests that current diagnostic criteria for BP fail to include milder but clinically significant syndromes. The application of the subthreshold bipolarity concept in a growing number of population surveys reveals that between 4% and 6% of adults may in fact manifest these conditions.1518 However, a significant percentage of subthreshold BP cases are diagnosed by default as unipolar major depression using current criteria.17,19,20 Expanding the definition of bipolarity is supported by prospective findings for a high probability of conversion to BP in youths with subthreshold mania18 as well as by findings from the National Comorbidity Survey Replication that indicate uniform increases in spectrum of severity and impairment across subthreshold BP, BP-II, and BP-I categories.17 Investigations of depression and mania symptom severity associated with subthreshold BP conditions further suggest that this category encompasses clinically significant manifestations that are comparable to people seeking treatment for BP in outpatient settings.21

Few prior international studies of BP have included information on severity or disability associated with this condition. Such information is necessary to facilitate cross-country analyses of comparable disorders and to help inform allocation of health services to populations with poor access to treatment, particularly in low-income countries.22 This article presents the lifetime and 12-month prevalence rates, patterns of comorbidity, impact, and use of mental health services for the BP spectrum (BPS) (BP-I, BP-II, and subthreshold BP) in the World Mental Health (WMH) Survey Initiative, a project of the World Health Organization that aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders in high-, middle-, and low-income countries (http://www.hcp.med.harvard.edu/wmh/). The major aims of this article are the following: (1) to present the cross-national prevalence estimates of BP using common diagnostic methods; (2) to test the validity of the spectrum concept of BP based on clinical severity, impairment, and comorbidity patterns; and (3) to examine cross-national service patterns for BPS.

SAMPLES

Eleven population-based surveys were carried out in the Americas (São Paulo metropolitan area, Brazil; Colombia; Mexico; and United States), Europe (Bulgaria and Romania), Asia (Shenzhen, People's Republic of China; Pondicherry region, India; and 9 metropolitan areas in Japan), Lebanon, and New Zealand. With the exception of Japan (unclustered 2-stage probability sample), all surveys were based on stratified multistage clustered area probability samples. Interviews were carried out face-to-face by trained lay interviewers on household residents aged 18 years and older (except aged ≥16 years in New Zealand and ≥20 years in Japan). Sample sizes ranged from 2357 (Romania) to 12 790 (New Zealand). Response rates ranged from 59.2% (Japan) to 98.8% (India), with an average response rate of 75.0%23 (Table 1).

Table Graphic Jump LocationTable 1. World Mental Health Surveys Sample Characteristics
PROCEDURES

In each participating country, the survey investigators and supervisors who were fluent in English and their local languages received standardized World Health Organization CIDI training at the Institute for Social Research, University of Michigan, Ann Arbor, on the use of the survey instrument and survey procedures.25 They were also involved in translation of the instrument and training materials for interviewers in their survey sites according to the translation protocol of the World Health Organization Surveys, carried out exclusively in the official languages of each country. Persons who could not speak these languages were excluded. Quality control protocols were standardized across countries to check interviewers' reliability and to specify data cleaning and coding procedures. The institutional review board of the organization that coordinated the survey in each country approved and monitored compliance with procedures for obtaining informed consent and protecting participants' identification.

MEASURES

All surveys used the WMH Survey Initiation version of the World Health Organization CIDI, version 3.0, a fully structured diagnostic interview composed of 2 parts to reduce respondent burden and survey costs. Part 1 constituted the core diagnostic assessment of various mental disorders including major depressive disorder and BPs. Part 2 included additional information relevant to a wide range of survey objectives. All respondents completed part 1, and those meeting criteria for any core mental disorder plus a probability sample of other respondents were administered part 2. The part 1 sample was weighted to adjust for the probability of selection and nonresponse and was poststratified to approximate the general population distribution regarding sex and age among other characteristics. Part 2 respondents were also weighted by the inverse of their probability of selection for part 2 of the interview to adjust for differential sampling. Methodological evidence collected in the WMH CIDI field trials and later clinical calibration studies showed that all of the disorders considered here were assessed with acceptable reliability and validity. Manic episodes, hypomanic episodes, and major depressive episodes (MDEs) were assessed according to DSM-IV criteria.

BP DISORDERS

Respondents were classified as having lifetime BP-I if they ever had a manic episode, defined by a period of 7 days or longer with elevated mood plus 3 other mania-related symptoms or with irritable mood plus 4 other mania-related symptoms, with the mood disturbance resulting in marked impairment, need for hospitalization, or psychotic features. Respondents were classified as having lifetime BP-II if they had both MDEs and a hypomanic episode, defined by a period of 4 days or longer with symptom criteria similar to mania and with an unequivocal change in functioning but without a manic episode. Criteria for subthreshold hypomania included the presence of at least 1 symptom on the screening questions for mania and failure to meet the full diagnostic criteria for hypomania. In the remainder of this article, BPD refers to people with either BP-I or BP-II, and BPS refers to those with BP spectrum comprised of BP-I, BP-II, or subthreshold BP. The DSM-IV requirement that symptoms do not meet criteria for a mixed episode was not operationalized in making these diagnoses.

Among respondents with lifetime BP-I or BP-II, those reporting an MDE or a manic or hypomanic episode at any time in the 12 months before the interview were classified as having 12-month BPD. The number of manic or hypomanic episodes and MDEs in this 12-month period was assessed. For those having episodes in the past 12 months, symptom severity and role impairment were also assessed. Symptom severity for the most severe month in the past 12 months was assessed with the self-report versions of the Young Mania Rating Scale (YMRS)26,27 for mania or hypomania and the Quick Inventory of Depressive Symptoms (QIDS)28 for MDEs. We defined the level of severity for manic or hypomanic episodes and MDEs as severe (YMRS score >24, QIDS score >15), moderate (YMRS score >14 to 24, QIDS score >10 to 15), mild (YMRS score >8 to 14, QIDS score >5 to 10), or clinically nonsignificant (YMRS score 0-8, QIDS score 0-5). Role impairment was assessed with the Sheehan Disability Scale.29 Respondents were asked to focus on the months in the past year when their manic or hypomanic episode or MDE was most severe and to rate how much the condition interfered with their home management, work, social life, and close relationships using a visual analogue scale scored from 1 to 10. Impairment was scored as none (0), mild (1-3), moderate (4-6), severe (7-9), or very severe (10). Clinical features such as age at onset, course, longest lifetime episode, and number of months in the episode during the previous year were assessed separately for manic or hypomanic episodes and MDEs.

OTHER DISORDERS

Assessment of other DSM-IV disorders or symptoms included anxiety disorders (generalized anxiety disorder, panic attacks, panic disorder and/or agoraphobia, posttraumatic stress disorder, obsessive-compulsive disorder, specific phobia, social phobia, separation anxiety disorder), impulse control disorders (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, intermittent explosive disorder), and substance-related disorders (alcohol abuse and dependence, drug abuse and dependence). Organic exclusion rules and diagnostic hierarchy rules were used in making all diagnoses (ie, the diagnosis was not made if the respondent indicated that the episode of depression or mania was due to physical illness or injury or use of medication, drugs, or alcohol).

CLINICAL REAPPRAISAL OF CIDI DISORDER

Blinded clinical reappraisal interviews using the nonpatient version of the Structured Clinical Interview for DSM-IV30 with a probability subsample of respondents in the US National Comorbidity Survey Replication found generally good concordance of CIDI and DSM-IV diagnoses of anxiety, mood, and substance-related disorders with independent clinical assessments.14 Systematic evaluation of the validity of the assessment of BPS in the WMH CIDI yielded excellent concordance between the Structured Clinical Interview for DSM-IV and CIDI diagnoses of BP-I and either BP-II or subthreshold BP21 but poor ability to distinguish between the latter 2 categories. This demonstrates the importance of including subthreshold BP in characterizing the full spectrum of expression of BP in community settings.

OTHER MEASURES

We also considered the association of BPD with sociodemographic variables at the time of interview, such as sex, age (ages 18-34, 35-49, 50-64, ≥65 years), marital status (married, previously married, never married), education level compared with the local country standard (low, low-average, high-average, high), employment status (working, student, homemaker, retired, other [including unemployed]), and household income compared with the local country standard (low, low-average, high-average, high). Results are not presented by income level for all of the analyses, but differences are described in the text when relevant. Cross-country treatment rates are presented by income levels because of international variation in the availability of mental health services. All part 2 respondents were asked about 12-month and lifetime treatment of any problem concerning emotions, nerves, or substance use by a psychiatrist, other mental health professional (psychologist, psychotherapist, psychiatric nurse), general medical provider, human services professional, and complementary and alternative medicine provider (eg, acupuncturist, chiropractor, spiritual healer). They were also asked about treatment specific to MDE and/or mania or hypomania, whether the treatment was helpful or effective, hospitalization for MDE and/or mania or hypomania, and use of indicated medications such as mood stabilizers, antidepressants, or antipsychotics.

STATISTICAL ANALYSIS

Age at onset and projected lifetime risk as of age 75 years were estimated using the actuarial method implemented in SAS version 8.2 statistical software (SAS Institute, Inc, Cary, North Carolina).31 Standard errors were estimated using the Taylor series linearization method implemented in the SUDAAN software system (Research Triangle Institute, Research Triangle Park, North Carolina). Multivariate significance tests were made with Wald χ2 tests using Taylor series design-based coefficient variance-covariance matrices. Standard errors of lifetime risk were estimated using the jackknife repeated replication method32,33 implemented in an SAS macro.33 Significance tests were all evaluated at the P = .05 level with 2-sided tests.

LIFETIME AND 12-MONTH PREVALENCE AND AGE AT ONSET

The lifetime prevalence rates of BP-I, BP-II, and subthreshold BP from the pooled sample of 11 countries were 0.6%, 0.4%, and 1.4%, respectively (Table 2). The 12-month prevalences of BP-I, BP-II, and subthreshold BP were 0.4%, 0.3%, and 0.8%, respectively. The United States had the highest lifetime and 12-month prevalence of BPS (4.4% and 2.8%, respectively), while India had the lowest (both 0.1%). Exceptions were found for Japan, a high-income country with very low lifetime and 12-month prevalences of BPS (0.7% and 0.2%, respectively), and Colombia, a low-income country with high lifetime prevalence of BPS (2.6%). Lifetime rates of BP-I and subthreshold BP were greater in males than in females, whereas females had higher rates of BP-II than their male counterparts. Marital status and employment status but not family income were significantly associated with BPS.

Table Graphic Jump LocationTable 2. Cross-National Lifetime and 12-Month Prevalence of Major Depressive Episodes and Bipolar Spectrum Disorders

The cumulative lifetime risk of BPS subtypes is shown in the Figure. Approximately half of those with BP-I and subthreshold BP report onset before age 25 years, and those with BP-II report a slightly later age at onset. However, there was a direct increase in the mean age at onset with less severe subtypes of BPS; the mean (SE) ages at onset were 18.4 (0.7) years for BP-I, 20.0 (0.6) years for BP-II, and 21.9 (0.4) years for subthreshold BP.

Place holder to copy figure label and caption
Figure.

Cumulative age-at-onset distributions of bipolar disorder type I (BP-I), bipolar disorder type II (BP-II), and subthreshold bipolar disorder (BP) among respondents projected to develop these disorders in their lifetime.

Graphic Jump Location
LIFETIME COMORBIDITY WITH OTHER DSM-IV DISORDERS

Three-quarters of those with BPS also met criteria for another lifetime disorder, more than half of whom had 3 or more other disorders (Table 3). Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (62.9%), followed by behavior disorders (44.8%) and substance use disorders (36.6%). There were significantly greater rates of comorbid disorders among those with BP-I (88.2%) and BP-II (83.1%) than among those with subthreshold BP (69.1%), although the odds of comorbid disorders were still significantly elevated for those with subthreshold BP relative to those without BP. Patterns of comorbidity with anxiety disorders and substance use disorders were remarkably similar across countries, whereas rates of comorbid behavior disorders were substantially higher in the United States and New Zealand compared with most other countries.

Table Graphic Jump LocationTable 3. Lifetime Comorbidity of DSM-IV and Composite International Diagnostic Interview Bipolar Spectrum Disorders With Other Disorders
CLINICAL SEVERITY

The vast majority of persons with BPS during the past 12 months reported severe or moderate manic or hypomanic episodes or MDEs in the past year (Table 4). Combined manic or hypomanic episodes and MDEs in the past 12 months were more severe among persons with BP-I (74.5%) and BP-II (68.8%) than among those with subthreshold BP (42.5%). The severity of MDEs was greater among those from low-income countries (95.5%) and medium-income countries (77.4%) than those in high-income countries (68.5%), whereas the severity of mania was comparable across low- and middle-income countries and slightly higher in high-income countries.

Table Graphic Jump LocationTable 4. Clinical Characteristics of Respondents With 12-Month DSM-IV Bipolar Spectrum Disorders
ROLE IMPAIRMENT

The aggregate proportions of severity levels of role impairment as assessed by the Sheehan Disability Scale by BP subtypes are presented in Table 4. The proportion of respondents with severe and very severe role impairment was greater for depression (74.0%) than for mania (50.9%). Severe and very severe role impairment was greater in high-income countries for both mania (57.3%) and depression (84.9%) than in medium-income countries (49.0% for mania; 58.7% for depression) and low-income countries (30.4% for mania; 55.1% for depression).

SUICIDE ATTEMPTS

Suicidal behaviors among those with BPS during the past 12 months are shown in Table 4. Similar to the other clinical indicators of severity, there was an increasing proportion of persons with suicidal behaviors with increasing levels of BPS. One in every 4 persons with BP-I, 1 in 5 of those with BP-II, and 1 in 10 of those with subthreshold BP reported a history of suicide attempts.

LIFETIME AND 12-MONTH TREATMENT

A substantially greater proportion of respondents with any BPS from high-income countries reported mental health service use (50.2% lifetime; 28.4% in the past 12 months) than those in middle-income countries (33.9% lifetime; 15.9% in the past 12 months) or low-income countries (25.2% lifetime; 13.0% in the past 12 months) (Table 5 and Table 6). Most respondents used mental health specialty sectors, followed by the general medical sector, and smaller proportions used human services and complementary and alternative medicine. Significantly greater proportions of those with BP-I (51.6%) and BP-II (59.9%) reported mental health specialty treatment than those with subthreshold BP (33.3%). Similar findings emerged for 12-month treatment.

Table Graphic Jump LocationTable 5. Lifetime Treatment of Bipolar Spectrum Disorders
Table Graphic Jump LocationTable 6. Twelve-Month Treatment of Bipolar Spectrum Disorders

To our knowledge, this article presents the first international data on the prevalence of DSM-IV BP and the broader BPS using common diagnostic procedures and methods. In a combined sample of 61 392 adults from 11 countries, the total lifetime prevalences were 0.6% for BP-I, 0.4% for BP-II, and 1.4% for subthreshold BP, yielding a total BPS prevalence estimate of 2.4% worldwide. Comparable 12-month prevalence rates were 0.4% for BP-I, 0.3% for BP-II, and 0.8% for subthreshold BP, with a total 12-month BPS prevalence of 1.5%. These rates are somewhat lower than those from earlier reviews of European studies4 and international studies,8 which yielded aggregate estimates of 1.5% and 0.8% for BP-I and BP-II, respectively, but with a far wider range of estimates than those reported here. In fact, variation in prevalence rates in these studies was attributed primarily to differences in the diagnostic interviews and definitions that were used to characterize BP.6 The use of common diagnostic definitions in the WMH reduces the methodologic diversity that has hindered international prevalence estimates and prevented accurate descriptions of the personal and economic impacts of this disorder.4

These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity.34 There was a direct association between increasingly restrictive definitions of BP and indicators of clinical severity including symptom severity, role impairment, comorbidity, suicidality, and treatment. For example, the proportion of mood episodes rated as clinically severe increased from 42.5% for subthreshold BP to 68.8% for BP-II to 74.5% for BP-I, and the proportion of cases reporting severe role impairment ranged from 46.3% for subthreshold BP to 57.1% for BP-I. These findings also confirm those of previous epidemiologic surveys that have highlighted pervasive comorbidity between BP and other mental disorders.10,35 Despite the differences in prevalence rates of comorbid disorders across countries, nearly three-quarters of those with BP-I or BP-II and more than half of those with BPS have a history of 3 or more disorders. With respect to specific types of conditions, the association of BP with anxiety disorders, particularly panic attacks, was notable; 62.9% of those with BPS have an anxiety disorder, with nearly half reporting panic attacks and about one-third meeting criteria for a phobic disorder. Confirmation of a strong link between BP and anxiety is particularly interesting in light of results from prospective studies of adolescents36 and follow-up studies of children of parents with BP suggesting that anxiety disorders may constitute an early form of expression of the developmental pathway of BPs.37,38

There was striking similarity in patterns of comorbidity of BPS with substance use disorders despite large differences in cross-national prevalence rates of substance use and abuse. The strong association of BP with substance use disorders has also been widely described in both community and clinical samples.39 Recent findings from a 20-year prospective cohort study revealed a dramatic increase in risk of alcohol dependence associated with symptoms of mania and BP in early adulthood.40 This suggests that BP can be considered a risk factor for the development of substance use disorders, which has important implications for prevention efforts. These findings also support the need for careful probing of a history of bipolarity among those with substance use disorders.

Finally, the large proportion of those with severe symptoms and role impairment demonstrates the serious nature of BP that has been well established in prior clinical and population-based surveys. Three-quarters of those with BPS reported severe levels of depressive symptoms and a comparable magnitude of severe role impairment. Most striking, 1 in every 4 or 5 persons with BPD had made suicide attempts. When taken together with the early age at onset and strong association with other mental disorders, these results provide further documentation of the individual and societal disability associated with this disorder.17,41,42 The finding that more than half of those with BP in adulthood date their onset to adolescence highlights the importance of early detection and intervention and possibly the importance of prevention of subsequent comorbid disorders. Because BP has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability. In light of the disability associated with BP, the lack of mental health treatment among those with BP, particularly in low-income countries, is alarming. Only one-quarter of those with BP in low-income countries and only half of those in high-income countries had contacted mental health services. Previous findings of service use in the WMH surveys described the large gap between the burden of mental disorders and mental health care in the studies participating in the WMH Survey Initiative.22 However, it is notable that most of those with BP received treatment in the mental health sector, even in low-income countries.

Interpretations of our findings must take account of the following conceptual and methodological issues. First, the surveys are cross-sectional, so the findings are based on retrospective recall of symptoms, age at onset, and clinical correlates. Such recall bias may differ by variation in the age composition across countries. Second, despite the use of common interview and diagnostic methods, there was still substantial cross-national variation in the rates of BPS. Although it is possible that these differences reflect real variation in prevalence perhaps owing to higher false-negatives in countries with greater stigma associated with mental illness, further inspection of these differences suggested that there was also variation in the translation, implementation, and quality control in some countries that may have led to reduced prevalence rates. Because there were major cross-country differences in social structure, we could not adequately control for social status, income, educational level, and other potentially relevant correlates of mental disorders. Third, although we found evidence for the validity of the diagnosis of BPS based on the CIDI compared with clinical reappraisal interviews (k = 0.94),21 comparable clinical validation studies were not carried out in all of the participating WMH countries. Fourth, the lack of information on mixed episodes of BP may have led to inaccurate estimates of the aggregate prevalence of either BP or major depression.

There are also several features of the WMH Survey Initiative that represent advances over prior cross-national studies in psychiatric epidemiology. First, the WMH initiative includes a far larger representation of several regions of the world, including low-income countries. Second, the high degree of coordination across studies enhanced the validity of the cross-national comparisons. Third, the inclusion of standardized methods for assessing severity and role impairment facilitates estimation that can provide a context for the public health significance of the prevalence estimates.

These findings demonstrate the important growth of international collaborations that permit investigation of cultural and regional differences in prevalence and risk factors for mental disorders. Recent efforts such as the proposal of a common global nomenclature to define the course and outcome in BPs as proposed by a task force under the auspices of the International Society for Bipolar Disorders43 should facilitate outcome studies across geographic areas. Contemporary issues concerning BP that warrant further study include the following: further evaluation of the thresholds and boundaries of BP; better integration of adult and child epidemiology of BP and its evolution in light of its onset in adolescence; and further investigation of explanations for the patterns of comorbidity between BP and other disorders. In summary, this article reports the first data, to our knowledge, on the prevalence and correlates of the full spectrum of BP in a series of nationally representative surveys using common methods. As such, it documents the magnitude and major impact of BP worldwide and underscores the urgent need for increased recognition and treatment facilitation.

Correspondence: Kathleen R. Merikangas, PhD, National Institute of Mental Health, Genetic Epidemiology Research Branch, Bldg 35, Room 1A201, 35 Convent Dr, MSC 3720, Bethesda, MD 20892 (kathleen.merikangas@nih.gov).

Submitted for Publication: May 16, 2010; final revision received November 17, 2010; accepted November 19, 2010.

Financial Disclosure: Drs Merikangas and He are with the Intramural Research Program of the National Institute of Mental Health. Dr Kessler has been a consultant for GlaxoSmithKline, Kaiser Permanente, Pfizer, Sanofi-Aventis, Shire Pharmaceuticals, and Wyeth-Ayerst; has served on advisory boards for Eli Lilly and Co and Wyeth-Ayerst; and has received research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, Johnson and Johnson Pharmaceuticals, Ortho-McNeil Pharmaceutical, Pfizer, and Sanofi-Aventis.

Funding/Support: This work was supported in part by the Intramural Research Program of the National Institute of Mental Health and was supported by grant R01MH070884 from the National Institute of Mental Health, the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, grants R13-MH066849, R01-MH069864, and R01 DA016558 from the US Public Health Service, grant FIRCA R03-TW006481 from the Fogarty International Center, the Pan American Health Organization, the Eli Lilly and Co Foundation, Ortho-McNeil Pharmaceutical, GlaxoSmithKline, Sanofi-Aventis, and Bristol-Myers Squibb. The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation Thematic Project Grant 03/00204-3. The Bulgarian Epidemiological Study of common mental disorders is supported by the Ministry of Health and the National Center for Public Health Protection. The Shenzhen Mental Health Survey is supported by the Shenzhen Bureau of Health and the Shenzhen Bureau of Science, Technology, and Information. The Colombian National Study of Mental Health is supported by the Ministry of Social Protection. World Mental Health India was funded by the World Health Organization (India) and helped by Dr R. Chandrasekaran, Jawaharlal Institute of Postgraduate Medical Education and Research. The World Mental Health Japan Survey is supported by Grants for Research on Psychiatric and Neurological Diseases and Mental Health H13-SHOGAI-023, H14-TOKUBETSU-026, and H16-KOKORO-013 from the Japan Ministry of Health, Labour and Welfare. The Lebanese National Mental Health Survey is supported by the Lebanese Ministry of Public Health, the World Health Organization (Lebanon), Fogarty International, anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from Janssen Cilag, Eli Lilly and Co, GlaxoSmithKline, Roche, and Novartis. The Mexican National Comorbidity Survey is supported by grant INPRFMDIES 4280 from the National Institute of Psychiatry Ramon de la Fuente and grant CONACyT-G30544-H from the National Council on Science and Technology, with supplemental support from the Pan American Health Organization. Te Rau Hinengaro: The New Zealand Mental Health Survey is supported by the New Zealand Ministry of Health, the Alcohol Advisory Council, and the Health Research Council. The Romania WMH study projects “Policies in Mental Health Area” and “National Study Regarding Mental Health and Services Use” were carried out by the National School of Public Health and Health Services Management (formerly the National Institute for Research and Development in Health), received technical support from Metro Media Transilvania, the National Institute of Statistics–National Centre for Training in Statistics, SC Cheyenne Services SRL, and Statistics Netherlands, and were funded by the Ministry of Public Health (formerly the Ministry of Health), with supplemental support from Eli Lilly Romania SRL. The US National Comorbidity Survey Replication is supported by grant U01-MH60220 from the National Institute of Mental Health, with supplemental support from the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, grant 044708 from the Robert Wood Johnson Foundation, and the John W. Alden Trust.

Disclaimer: The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or US government.

Additional Information: A complete list of WMH publications can be found at http://www.hcp.med.harvard.edu/wmh/.

Additional Contributions: The WMH Surveys are carried out in conjunction with the World Health Organization WMH Survey Initiative. We thank the WMH staff for assistance with instrumentation, fieldwork, and data analysis.

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Bauer  MPfennig  A Epidemiology of bipolar disorders. Epilepsia 2005;46(suppl 4)8- 13
PubMed
Pini  Sde Queiroz  VPagnin  DPezawas  LAngst  JCassano  GBWittchen  HU Prevalence and burden of bipolar disorders in European countries. Eur Neuropsychopharmacol 2005;15 (4) 425- 434
PubMed
Sherazi  RMcKeon  PMcDonough  MDaly  IKennedy  N What's new? the clinical epidemiology of bipolar I disorder. Harv Rev Psychiatry 2006;14 (6) 273- 284
PubMed
Waraich  PGoldner  EMSomers  JMHsu  L Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry 2004;49 (2) 124- 138
PubMed
Goodwin  FJamison  K Manic-Depressive Illness. 2nd London, England Oxford University Press2007;
Merikangas  KRPato  M Recent developments in the epidemiology of bipolar disorder in adults and children: magnitude, correlates, and future directions. Clin Psychol Sci Pract 2009;16 (2) 121- 133doi:10.1111/j.1468-2850.2009.01152.x
Gureje  OLasebikan  VOKola  LMakanjuola  VA Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of Mental Health and Well-Being. Br J Psychiatry 2006;188465- 471
PubMed
Grant  BFStinson  FSHasin  DSDawson  DAChou  SPRuan  WJHuang  B Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66 (10) 1205- 1215
PubMed
Kramer  M Cross-national study of diagnosis of the mental disorders: origin of the problem. Am J Psychiatry 1969;10(suppl)1- 11
PubMed
Zubin  J Cross-national study of diagnosis of the mental disorders: methodology and planning. Am J Psychiatry 1969;10(suppl)12- 20
PubMed
Cooper  JEKendell  REGurland  BSharpe  LCopeland  JRMSimon  R Psychiatric Diagnosis in New York and London: A Comparative Study of Mental Hospital Admissions.  London, England Oxford University Press1972;
Kessler  RCAbelson  JDemler  OEscobar  JIGibbon  MGuyer  MEHowes  MJJin  RVega  WAWalters  EEWang  PZaslavsky  AZheng  H Clinical calibration of DSM-IV diagnoses in the World Mental Health (WMH) version of the World Health Organization (WHO) Composite International Diagnostic Interview (WMHCIDI). Int J Methods Psychiatr Res 2004;13 (2) 122- 139
PubMed
Angst  JGamma  ALewinsohn  P The evolving epidemiology of bipolar disorder. World Psychiatry 2002;1 (3) 146- 148
PubMed
Judd  LLAkiskal  HS The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases. J Affect Disord 2003;73 (1-2) 123- 131
PubMed
Merikangas  KRAkiskal  HSAngst  JGreenberg  PEHirschfeld  RMPetukhova  MKessler  RC Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007;64 (5) 543- 552
PubMed
Zimmermann  PBrückl  TNocon  APfister  HLieb  RWittchen  HUHolsboer  FAngst  J Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry 2009;66 (12) 1341- 1352
PubMed
Angst  JGamma  ABenazzi  FAjdacic  VEich  DRössler  W Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord 2003;73 (1-2) 133- 146
PubMed
Angst  J The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50 (2-3) 143- 151
PubMed
Kessler  RCAkiskal  HSAngst  JGuyer  MHirschfeld  RMMerikangas  KRStang  PE Validity of the assessment of bipolar spectrum disorders in the WHO CIDI 3.0. J Affect Disord 2006;96 (3) 259- 269
PubMed
Wang  PSAngermeyer  MBorges  GBruffaerts  RTat Chiu  Wde Girolamo  GFayyad  JGureje  OHaro  JMHuang  YKessler  RCKovess  VLevinson  DNakane  YOakley Brown  MAOrmel  JHPosada-Villa  JAguilar-Gaxiola  SAlonso  JLee  SHeeringa  SPennell  BEChatterji  SUstün  TB Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization's World Mental Health Survey Initiative. World Psychiatry 2007;6 (3) 177- 185
PubMed
Heeringa  S Sampling designs and sampling procedures. RC  KesslerIn: eds.The WHO World Mental Health Surveys: Global Perspectives on the Epidemiology of Mental Disorders. New York, NY Cambridge University Press2008;14- 32
World Bank, Data and statistics, 2008. http://data.worldbank.org/about/country-classifications/country-and-lending-groupsAccessed September 172008;
Pennell  BE Implementation of the World Mental Health Surveys. RC  KesslerIn: eds.The WHO World Mental Health Surveys: Global Perspectives on the Epidemiology of Mental Disorders. New York, NY Cambridge University Press2008;33- 57
Young  RCBiggs  JTZiegler  VEMeyer  DA A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978;133429- 435
PubMed
Gracious  BLYoungstrom  EAFindling  RLCalabrese  JR Discriminative validity of a parent version of the Young Mania Rating Scale. J Am Acad Child Adolesc Psychiatry 2002;41 (11) 1350- 1359
PubMed
Rush  AJTrivedi  MHIbrahim  HMCarmody  TJArnow  BKlein  DNMarkowitz  JCNinan  PTKornstein  SManber  RThase  MEKocsis  JHKeller  MB The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54 (5) 573- 583
PubMed
Leon  ACOlfson  MPortera  LFarber  LSheehan  DV Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med 1997;27 (2) 93- 105
PubMed
First  MSpitzer  RGibbon  MWilliams  J Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP).  New York Biometrics Research Dept, New York State Psychiatric Institute2002;
SAS Institute, Inc, SAS/STAT Software: Changes and Enhancements, Release 8.2.  Cary, NC SAS Publishing2001;
Halli  SRao  KHalli  S Advanced Techniques of Population Analysis.  New York, NY Plenum Press1992;
Wolter  K Introduction to Variance Estimation.  New York, NY Springer-Verlag1985;
Angst  JCui  LSwendsen  JRothen  SCravchik  AKessler  RCMerikangas  KR Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry 2010;167 (10) 1194- 1201
PubMed
Keller  MB Prevalence and impact of comorbid anxiety and bipolar disorder. J Clin Psychiatry 2006;67(suppl 1)5- 7
PubMed
Lewinsohn  PMSeeley  JRBuckley  MEKlein  DN Bipolar disorder in adolescence and young adulthood. Child Adolesc Psychiatr Clin N Am 2002;11 (3) 461- 475, vii
PubMed
Duffy  AAlda  MCrawford  LMilin  RGrof  P The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents. Bipolar Disord 2007;9 (8) 828- 838
PubMed
Henin  ABiederman  JMick  ESachs  GSHirshfeld-Becker  DRSiegel  RSMcMurrich  SGrandin  LNierenberg  AA Psychopathology in the offspring of parents with bipolar disorder: a controlled study. Biol Psychiatry 2005;58 (7) 554- 561
PubMed
Strakowski  SMDelBello  MP The co-occurrence of bipolar and substance use disorders. Clin Psychol Rev 2000;20 (2) 191- 206
PubMed
Merikangas  KRHerrell  RSwendsen  JRössler  WAjdacic-Gross  VAngst  J Specificity of bipolar spectrum conditions in the comorbidity of mood and substance use disorders: results from the Zurich cohort study. Arch Gen Psychiatry 2008;65 (1) 47- 52
PubMed
Wittchen  HUMhlig  SPezawas  L Natural course and burden of bipolar disorders. Int J Neuropsychopharmacol 2003;6 (2) 145- 154
PubMed
Morgan  VAMitchell  PBJablensky  AV The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) Disorders. Bipolar Disord 2005;7 (4) 326- 337
PubMed
Tohen  MFrank  EBowden  CLColom  FGhaemi  SNYatham  LNMalhi  GSCalabrese  JRNolen  WAVieta  EKapczinski  FGoodwin  GMSuppes  TSachs  GSChengappa  KRGrunze  HMitchell  PBKanba  SBerk  M The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 2009;11 (5) 453- 473
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Cumulative age-at-onset distributions of bipolar disorder type I (BP-I), bipolar disorder type II (BP-II), and subthreshold bipolar disorder (BP) among respondents projected to develop these disorders in their lifetime.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. World Mental Health Surveys Sample Characteristics
Table Graphic Jump LocationTable 2. Cross-National Lifetime and 12-Month Prevalence of Major Depressive Episodes and Bipolar Spectrum Disorders
Table Graphic Jump LocationTable 3. Lifetime Comorbidity of DSM-IV and Composite International Diagnostic Interview Bipolar Spectrum Disorders With Other Disorders
Table Graphic Jump LocationTable 4. Clinical Characteristics of Respondents With 12-Month DSM-IV Bipolar Spectrum Disorders
Table Graphic Jump LocationTable 5. Lifetime Treatment of Bipolar Spectrum Disorders
Table Graphic Jump LocationTable 6. Twelve-Month Treatment of Bipolar Spectrum Disorders

References

World Health Organization, The World Health Report 2002: Reducing Risks, Promoting Healthy Life.  Geneva, Switzerland World Health Organization2002;
Weissman  MMBland  RCCanino  GJFaravelli  CGreenwald  SHwu  HGJoyce  PRKaram  EGLee  CKLellouch  JLépine  JPNewman  SCRubio-Stipec  MWells  JEWickramaratne  PJWittchen  HYeh  EK Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276 (4) 293- 299
PubMed
Bauer  MPfennig  A Epidemiology of bipolar disorders. Epilepsia 2005;46(suppl 4)8- 13
PubMed
Pini  Sde Queiroz  VPagnin  DPezawas  LAngst  JCassano  GBWittchen  HU Prevalence and burden of bipolar disorders in European countries. Eur Neuropsychopharmacol 2005;15 (4) 425- 434
PubMed
Sherazi  RMcKeon  PMcDonough  MDaly  IKennedy  N What's new? the clinical epidemiology of bipolar I disorder. Harv Rev Psychiatry 2006;14 (6) 273- 284
PubMed
Waraich  PGoldner  EMSomers  JMHsu  L Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry 2004;49 (2) 124- 138
PubMed
Goodwin  FJamison  K Manic-Depressive Illness. 2nd London, England Oxford University Press2007;
Merikangas  KRPato  M Recent developments in the epidemiology of bipolar disorder in adults and children: magnitude, correlates, and future directions. Clin Psychol Sci Pract 2009;16 (2) 121- 133doi:10.1111/j.1468-2850.2009.01152.x
Gureje  OLasebikan  VOKola  LMakanjuola  VA Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of Mental Health and Well-Being. Br J Psychiatry 2006;188465- 471
PubMed
Grant  BFStinson  FSHasin  DSDawson  DAChou  SPRuan  WJHuang  B Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66 (10) 1205- 1215
PubMed
Kramer  M Cross-national study of diagnosis of the mental disorders: origin of the problem. Am J Psychiatry 1969;10(suppl)1- 11
PubMed
Zubin  J Cross-national study of diagnosis of the mental disorders: methodology and planning. Am J Psychiatry 1969;10(suppl)12- 20
PubMed
Cooper  JEKendell  REGurland  BSharpe  LCopeland  JRMSimon  R Psychiatric Diagnosis in New York and London: A Comparative Study of Mental Hospital Admissions.  London, England Oxford University Press1972;
Kessler  RCAbelson  JDemler  OEscobar  JIGibbon  MGuyer  MEHowes  MJJin  RVega  WAWalters  EEWang  PZaslavsky  AZheng  H Clinical calibration of DSM-IV diagnoses in the World Mental Health (WMH) version of the World Health Organization (WHO) Composite International Diagnostic Interview (WMHCIDI). Int J Methods Psychiatr Res 2004;13 (2) 122- 139
PubMed
Angst  JGamma  ALewinsohn  P The evolving epidemiology of bipolar disorder. World Psychiatry 2002;1 (3) 146- 148
PubMed
Judd  LLAkiskal  HS The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases. J Affect Disord 2003;73 (1-2) 123- 131
PubMed
Merikangas  KRAkiskal  HSAngst  JGreenberg  PEHirschfeld  RMPetukhova  MKessler  RC Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007;64 (5) 543- 552
PubMed
Zimmermann  PBrückl  TNocon  APfister  HLieb  RWittchen  HUHolsboer  FAngst  J Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry 2009;66 (12) 1341- 1352
PubMed
Angst  JGamma  ABenazzi  FAjdacic  VEich  DRössler  W Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord 2003;73 (1-2) 133- 146
PubMed
Angst  J The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50 (2-3) 143- 151
PubMed
Kessler  RCAkiskal  HSAngst  JGuyer  MHirschfeld  RMMerikangas  KRStang  PE Validity of the assessment of bipolar spectrum disorders in the WHO CIDI 3.0. J Affect Disord 2006;96 (3) 259- 269
PubMed
Wang  PSAngermeyer  MBorges  GBruffaerts  RTat Chiu  Wde Girolamo  GFayyad  JGureje  OHaro  JMHuang  YKessler  RCKovess  VLevinson  DNakane  YOakley Brown  MAOrmel  JHPosada-Villa  JAguilar-Gaxiola  SAlonso  JLee  SHeeringa  SPennell  BEChatterji  SUstün  TB Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization's World Mental Health Survey Initiative. World Psychiatry 2007;6 (3) 177- 185
PubMed
Heeringa  S Sampling designs and sampling procedures. RC  KesslerIn: eds.The WHO World Mental Health Surveys: Global Perspectives on the Epidemiology of Mental Disorders. New York, NY Cambridge University Press2008;14- 32
World Bank, Data and statistics, 2008. http://data.worldbank.org/about/country-classifications/country-and-lending-groupsAccessed September 172008;
Pennell  BE Implementation of the World Mental Health Surveys. RC  KesslerIn: eds.The WHO World Mental Health Surveys: Global Perspectives on the Epidemiology of Mental Disorders. New York, NY Cambridge University Press2008;33- 57
Young  RCBiggs  JTZiegler  VEMeyer  DA A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978;133429- 435
PubMed
Gracious  BLYoungstrom  EAFindling  RLCalabrese  JR Discriminative validity of a parent version of the Young Mania Rating Scale. J Am Acad Child Adolesc Psychiatry 2002;41 (11) 1350- 1359
PubMed
Rush  AJTrivedi  MHIbrahim  HMCarmody  TJArnow  BKlein  DNMarkowitz  JCNinan  PTKornstein  SManber  RThase  MEKocsis  JHKeller  MB The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54 (5) 573- 583
PubMed
Leon  ACOlfson  MPortera  LFarber  LSheehan  DV Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med 1997;27 (2) 93- 105
PubMed
First  MSpitzer  RGibbon  MWilliams  J Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP).  New York Biometrics Research Dept, New York State Psychiatric Institute2002;
SAS Institute, Inc, SAS/STAT Software: Changes and Enhancements, Release 8.2.  Cary, NC SAS Publishing2001;
Halli  SRao  KHalli  S Advanced Techniques of Population Analysis.  New York, NY Plenum Press1992;
Wolter  K Introduction to Variance Estimation.  New York, NY Springer-Verlag1985;
Angst  JCui  LSwendsen  JRothen  SCravchik  AKessler  RCMerikangas  KR Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry 2010;167 (10) 1194- 1201
PubMed
Keller  MB Prevalence and impact of comorbid anxiety and bipolar disorder. J Clin Psychiatry 2006;67(suppl 1)5- 7
PubMed
Lewinsohn  PMSeeley  JRBuckley  MEKlein  DN Bipolar disorder in adolescence and young adulthood. Child Adolesc Psychiatr Clin N Am 2002;11 (3) 461- 475, vii
PubMed
Duffy  AAlda  MCrawford  LMilin  RGrof  P The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents. Bipolar Disord 2007;9 (8) 828- 838
PubMed
Henin  ABiederman  JMick  ESachs  GSHirshfeld-Becker  DRSiegel  RSMcMurrich  SGrandin  LNierenberg  AA Psychopathology in the offspring of parents with bipolar disorder: a controlled study. Biol Psychiatry 2005;58 (7) 554- 561
PubMed
Strakowski  SMDelBello  MP The co-occurrence of bipolar and substance use disorders. Clin Psychol Rev 2000;20 (2) 191- 206
PubMed
Merikangas  KRHerrell  RSwendsen  JRössler  WAjdacic-Gross  VAngst  J Specificity of bipolar spectrum conditions in the comorbidity of mood and substance use disorders: results from the Zurich cohort study. Arch Gen Psychiatry 2008;65 (1) 47- 52
PubMed
Wittchen  HUMhlig  SPezawas  L Natural course and burden of bipolar disorders. Int J Neuropsychopharmacol 2003;6 (2) 145- 154
PubMed
Morgan  VAMitchell  PBJablensky  AV The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) Disorders. Bipolar Disord 2005;7 (4) 326- 337
PubMed
Tohen  MFrank  EBowden  CLColom  FGhaemi  SNYatham  LNMalhi  GSCalabrese  JRNolen  WAVieta  EKapczinski  FGoodwin  GMSuppes  TSachs  GSChengappa  KRGrunze  HMitchell  PBKanba  SBerk  M The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 2009;11 (5) 453- 473
PubMed

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