 |
|
Diagnostic Reliability of Bipolar II Disorder
Sylvia G. Simpson, MD;
Francis J. McMahon, MD;
Melvin G. McInnis, MD;
Dean F. MacKinnon, MD;
David Edwin, PhD;
Susan E. Folstein, MD;
J. Raymond DePaulo, MD
Arch Gen Psychiatry. 2002;59:736-740.
ABSTRACT
| |
Background Although the diagnostic reliability of major depression and mania has
been well established, that of hypomania and bipolar II (BPII) disorder has
not. This remains an important issue for clinicians, especially for those
undertaking genetic studies of BP disorder since bipolar I (BPI) and BPII
disorders often cluster in the same families. We have assessed our diagnostic
reliability of BP disorders, recurrent unipolar disorder, and their constituent
episodes (major depression, mania, and hypomania) using interview and best-estimate
diagnostic procedures used in a genetic study of families with BPI disorder.
Methods Reliability was assessed for (1) co-rated Schedule for Affective Disorders
and Schizophrenia–Lifetime version interviews of 37 subjects including
15 with BP disorders; (2) test-retest Schedule for Affective Disorders and
Schizophrenia–Lifetime version interviews of 26 subjects including 13
with BP disorders; and (3) best-estimate diagnoses made by 2 noninterviewing
psychiatrists on 524 subjects in a genetic linkage study of BPI disorder.
Diagnoses were based on Research Diagnostic Criteria for
a Selected Group of Functional Disorders, except that recurrent major
depression as well as hypomania was required for a diagnosis of BPII disorder.
Results On co-rated interviews, we observed complete agreement between interviewers
for diagnosing major depressive, manic, and hypomanic episodes. For test-retest
interviews, the Cohen  coefficients were 0.83 for manic, 0.72 for hypomanic,
and 1.0 for major depressive episodes. At the best-estimate level, the Cohen
coefficients were 0.99 for BPI, 0.99 for BPII, and 0.98 for recurrent unipolar
disorder.
Conclusion Good interrater reliability for BPII can be achieved when the interviews
and best-estimate diagnoses are done by experienced psychiatrists.
INTRODUCTION
ALTHOUGH THE reliability of mania and major depression and their derivative
diagnoses, bipolar I (BPI) and recurrent unipolar (RUP) disorder, is well
established,1-2 there is controversy
about the reliability of the diagnosis of hypomania and bipolar II (BPII)
disorder.1 In clinical settings, individuals
with BPII usually present for treatment of depression. If the history of hypomanic
symptoms goes undetected, there is concern about the risks of treatment with
antidepressants alone. When asked about hypomanic symptoms, many patients
do not report them, either because the symptoms are not commented on by others
or because there is little impairment, and sometimes improved function, associated
with them.3 The symptoms of grandiosity and
poor judgment are often absent. There is a further source of doubt about the
diagnosis of BP disorder in these patients since they tend to have more comorbidity,
especially in the form of Axis II psychopathology.4-5
Individuals with BPII are prevalent in the families of probands with
BPI6-8 and represent
a large proportion of affectively ill relatives in our family study of BPI.9 The National Institute of Mental Health Collaborative
Study of the Psychobiology of Depression8, 10
and a later study by Heun and Maier11 reported
that relatives of probands with BPII are at significantly higher risk for
developing BPII than are relatives of probands with BPI or probands with RUP
disorders. Findings from these studies and 2 reports of single large sibships
in which BPII is the only affective disorder12-13
suggest that BPII should be considered as distinct from BPI and RUP disorders.
The concern about the reliability of the hypomania diagnosis was most
clearly presented by Andreasen et al1 in the
National Institute of Mental Health Psychobiology of Depression Study. This
study reported a reliability coefficient that was no greater than chance,
based on Schedule for Affective Disorders and Schizophrenia–Lifetime
version (SADS-L)14 interviews on a few subjects
done 6 months apart by trained nonphysician interviewers.
Experienced psychiatrists conduct the interviews in our family study
of BPI.7 We present reliability data at the
interview and best-estimate levels for BPI, BPII, and RUP diagnoses, based
on Research Diagnostic Criteria for a Selected Group of
Functional Disorders (RDC).15 The interview
data were collected specifically as a preparatory reliability exercise for
our family study of BPI, while the duplicate best-estimate diagnoses were
done primarily to ensure the accuracy of diagnoses used for our linkage analyses.
Molecular genetic data supporting the validity of our BPII diagnoses have
been reported by McMahon et al.16
SUBJECTS AND METHODS
SUBJECTS
In part 1 of the reliability study, we conducted 37 co-rated SADS-L
and 26 test-retest SADS-L interviews. The group of 37 co-rated subjects consisted
of 12 patients selected from the Johns Hopkins Hospital psychiatric inpatient
units and 25 participants from the family study of BPI. Six of the inpatients
had BP disorders (3 with BPI and 3 with BPII) compared with 9 of the family
subjects (5 of whom had BPI and 4 of whom had BPII). Sixty-one percent of
the co-rated subjects were female and 61% had been married (ie, "had been
married" includes currently married, separated, divorced, and widowed individuals).
Their mean age was 34.5 years and mean years of education was 13. Most of
the inpatients were recruited from units other than the affective disorders
unit. Subjects were excluded if their primary diagnosis was a substance use
disorder but not if this was a comorbid diagnosis. Most of the patients or
subjects with BP disorder and RUP had 1 or more comorbid diagnoses.
The 26 test-retest subjects consisted of inpatients, day-hospital patients,
and healthy control subjects and included 13 subjects with BP disorders (7
with BPI, and 6 with BPII). Of the 26, 17 (65%) were female and 16 (62%) had
been married; their mean age was 40 years and mean years of education was
14. Four of the 6 subjects having the diagnosis of BPII in the test-retest
study were young people in their early to mid-20s. This was the first hospitalization
for only 1 of the subjects, but for most it was the first time they had been
diagnosed as having BPII. These subjects with BPII were quite complex. Five
of the 6 had 1 or more substance use disorders, 3 had 1 or more anxiety disorders,
and 3 had an eating disorder. Healthy controls were recruited from among friends
and acquaintances of the research staff.
The subjects for part 2 of the reliability study, the assessment of
agreement between pairs of best-estimate diagnoses, were 524 relatives from
71 families in the Johns Hopkins BPI disorder family study.16
Fifty-five percent were female, 80% had ever been married, their mean age
was 45 years, and their mean years of education was 14.5. Forty-seven percent
were affected with a major affective disorder, 27% were unaffected, and 26%
had an uncertain phenotype. Twenty percent of the sample (104 subjects) had
BPI, 16% (86 subjects) had BPII, and 10% (55 subjects) had RUP. Family study
subjects were given information about BP disorder during the consent procedure
just prior to the interview but had not been otherwise educated by us regarding
BP disorders.
DIAGNOSTIC PROCEDURES
Diagnostic reliability was tested for interview diagnoses and best-estimate
diagnoses. All SADS-L interviews were done by 5 psychiatrists (S.G.S., F.J.M.,
M.G.M., D.F.M., and J.R.D.). Interviewers were blind to the subjects' diagnoses.
All pertinent RDC diagnoses, current and lifetime,
were made on all subjects. The paired test-retest interviews were done within
72 hours of each other, most of them within a 24-hour period. Interviews were
done by the first available psychiatrist, with no formal randomization as
to who did the test or retest interviews. Fifteen of the 26 test-retest interviews
were done by a more junior psychiatrist (S.G.S.), but this is unlikely to
introduce a systematic bias in favor of diagnosing hypomania. The interviewing
psychiatrists had no knowledge of family history or medical records on these
subjects.
The pairs of best-estimate diagnoses were made by the same 5 psychiatrists
(other than the interviewing psychiatrist) and a sixth senior psychiatrist
(S.E.F.) and were based on family-history data, treatment records, and the
direct interview,17 including a narrative summary
done by the interviewing psychiatrist. Specific best-estimate diagnoses were
assigned for major recurrent affective disorder diagnoses, while a best-estimate
diagnosis of "uncertain phenotype" was assigned if a subject had a single
episode of major depression or a minor affective diagnosis such as hypomania
or minor depression.
After each diagnostician separately assigned a best-estimate diagnosis,
the diagnosticians were allowed to discuss the case. In cases where the diagnosticians
did not agree, they were encouraged to rectify any incomplete or misreading
of family history data, medical records, or SADS-L data, and were also able
to question the interviewing psychiatrist to clarify information in the narrative
summary or to correct coding discrepancies in the interview.
If the diagnosticians still did not agree after a guided review of the
data, we did not encourage much less force agreement. For the purposes of
the linkage study, the subject was assigned the more "conservative" of the
2 diagnoses as the final consensus best-estimate diagnosis. For example, if
there was disagreement as to whether the subject had an affective disorder,
the subject was designated as having an uncertain phenotype. Nearly one quarter
of our sample has been so designated; in most cases, this was because they
either had a single episode of major depression or hypomania without recurrent
major depression. If there was disagreement between 2 affective disorder diagnoses,
for example, if one reviewer assigned a diagnosis of BPI and the other BPII,
the consensus final best-estimate would be BPII. The final diagnosis of each
reviewer, however, is retained in the database as a record of their disagreement.
STATISTICAL ANALYSES
Reliability was assessed using the unweighted Cohen statistic18 that measures agreement on nominal categories such
as diagnosis and that incorporates a correction for chance agreement. The
asymptotic SEs of the values and 2-tailed level of statistical significance
over a 95% confidence interval were calculated using the SPSS software package.19-20
RESULTS
DIAGNOSTIC RELIABILITY AT THE SADS-L INTERVIEW LEVEL
In the group of 37 subjects interviewed with co-rated SADS-L, there
was complete agreement between raters on the diagnoses of major depressive,
manic, and hypomanic episodes, with a score of 1.0 for each. Among
the 26 subjects evaluated by test-retest interviews, there was agreement among
raters that 19 had at least 1 major affective episode, 18 had recurrent episodes,
12 had a BP subtype, and 6 had BPII disorder. The values (SE) were
0.83 (0.11) for manic episodes, 0.72 (0.15) for hypomanic, and 1.0 (<0.001)
for major depressive episodes. All values were significant at the P<.001 level (see Table 1 for agreement on the hypomania diagnosis). There was disagreement
over the hypomania diagnosis in 3 of the 26 test-retest subjects. In 2 cases,
the interviewers differed on whether the subjects had ever experienced a hypomanic
episode. In the third, one interviewer diagnosed mania and the other diagnosed
hypomania.
|
|
|
|
Table 1. Agreement on Hypomania Diagnoses in Test-Retest SADS-L Interviews*
|
|
|
DIAGNOSTIC RELIABILITY AT THE BEST-ESTIMATE LEVEL
We compared affective disorder diagnoses assigned by pairs of noninterviewing
psychiatrists making best-estimate diagnoses on 524 members of families ascertained
through probands with BP disorder (Table
2). There was agreement on 98% of the affective disorder diagnoses.
The values (SE) for best-estimate diagnoses were 0.99 (0.006) for
BPI, 0.99 (0.007) for BPII, and 0.98 (0.014) for RUP. All values were
significant at the P<.001 level.
|
|
|
|
Table 2. Agreement Between Diagnosticians 1 and 2 on 524 Best-Estimate
Diagnoses
|
|
|
COMMENT
Our findings from the co-rated and test-retest SADS-L interviews indicate
that good interrater diagnostic reliability can be achieved for BPII if experienced
clinicians (in this case, psychiatrists) conduct the interviews. These results
are consistent with those of Dunner and Tay,21
but challenge the prevalent view that BPII cannot be diagnosed reliably. Although
our sample size for the test-retest study was modest and included mainly inpatients,
it included twice as many subjects with BPII as the sample that has been considered
the benchmark for reliability of the BPII diagnosis. The prevalent view that
the hypomania diagnosis has low reliability was based on a sample of 50 subjects
from the National Institute of Mental Health Psychobiology of Depression Study,1 only 3 of whom were diagnosed as having BPII. Those
subjects were interviewed twice, 6 months apart, and at time 2 they were interviewed
twice on the same day. There was good diagnostic agreement on hypomania on
the same-day interviews, with an intraclass correlation coefficient of 0.6,
but poor diagnostic agreement between the interviews done 6 months apart,
with an intraclass correlation coefficient of 0.06. In another study of similar
size, Mazure and Gershon22 did test-retest
SADS-L interviews 6 months apart and reported relatively good agreement, with
an overall of 0.79. Of the 3 subjects with hypomania, 2 were diagnosed
as hypomanic at both assessments, compared with 6 of 6 subjects diagnosed
with mania.
The hypomania diagnosis has been shown to have predictive power even
if made on only 1 of 2 interviews. In a group of relatives from the Psychobiology
of Depression Study who were interviewed 5 years apart,23
9 of 10 subjects who were diagnosed as having hypomania at one interview were
not diagnosed with it at the other interview, but all 10 cases predicted a
proband with BPI or BPII.
Conclusions regarding the reliability of the best-estimate diagnoses
must consider the limited independence of the best-estimate diagnosticians
in this study. Our procedures, which were devised to maximize diagnostic validity
for genetic studies, allow for some communication between reviewers. We compared
our best-estimate reliability study to a recent study by Maziade et al.24 They compared diagnoses made by psychiatrists in
the field based on a summary of all of the clinical data, to diagnoses made
by a board of research psychiatrists who were blind to the probands' and relatives'
diagnoses. Two research psychiatrists reviewed all available clinical data
and made best-estimate diagnoses independently, after which they discussed
the case. If they agreed, the complete record was presented to the board for
a final consensus diagnosis. If they disagreed, the complete record was reviewed
by 2 other psychiatrists, who made independent diagnoses and sent the case
to the board.
While there are many similarities with our diagnostic procedure, there
are also some differences. Our psychiatrist-interviewers make diagnoses based
only on the SADS-L interview. We have a panel of 6 psychiatrists (composed
of 6 of us) who serve as best-estimate diagnosticians, except on subjects
whom they had interviewed. Any 2 psychiatrists separately review all sources
of data and make their diagnoses. If there is a difference of opinion between
diagnosticians, they are allowed to discuss the case. This process allows
correctable errors, such as misreading of the clinical data, to be detected.
If the diagnosticians still do not agree, agreement is not forced, nor is
a third psychiatrist brought in as a tiebreaker. Instead, for the purpose
of assigning a phenotype for genetic study, the subject is given the more
"conservative" of the 2 diagnoses. By conservative we mean that if 1 reviewer
made the diagnosis of BPII (with recurrent major depression) and the other
made the diagnosis of RUP, we would assign RUP as the diagnosis. We, thus,
would capture the part of the diagnosis agreed on and would exclude the subject
from the narrowest affection status in the genetic analyses.
Applicability of our findings to clinical samples must be qualified
as follows. While most of the test-retest subjects and some of the co-rated
subjects were drawn from the general psychiatry inpatient units and are, therefore,
likely to reflect a representative clinical population, some of the co-rated
subjects were relatives of patients but not patients themselves. In addition,
the sample for the best-estimate reliability study consisted of patients with
BP and their relatives, some of whom were affected and some of whom were not,
and may not be representative of clinical samples. Our findings may not be
applicable to community-based, nontreatment seeking samples where reliability
might be considerably more variable.
In addition to using DSM-IV25
criteria, we believe it is important to continue to use the RDC in genetic studies of BP disorder so that findings can be compared
with those of earlier studies. "Probable hypomania" as defined by RDC requires a minimum of 2 manic symptoms for at least 2 days without
associated impairment, while DSM-IV requires 3 symptoms
for at least 4 days and an associated change in function that is observable
by others. While raising the diagnostic threshold will improve the reliability
of the hypomania diagnosis, raising the threshold may also decrease the sensitivity,
with milder episodes going undiagnosed.
CONCLUSIONS
We have demonstrated that experienced psychiatrists using a semistructured
interview such as the SADS-L can reliably diagnose BPII. This has important
implications for genetic studies of BP disorders since individuals with BPII
are prevalent in families ascertained through probands with BPI. Based on
clinical data from our family studies, we have proposed that BPII may be genetically
less complex than BPI and that identifying the subjects with BPII in these
families may be crucial to understanding the genetics of BP disorder generally.7 Furthermore, misdiagnosing BPII as recurrent unipolar
depression decreases the power of the sample to identify genes for BP disorder.
Misdiagnosing BPII as unipolar depression also has important clinical
implications, both for training of clinicians and for treatment. Treatment
with antidepressant medications alone may lead to a worsening of the course
of illness (with the possible development of mixed states or rapid-cycling)
and may also deprive the patient of the potential benefits of mood stabilizing
medications.
AUTHOR INFORMATION
Submitted for publication April 11, 2000; final revision received September
26, 2001; accepted October 1, 2001.
This study was supported by grants from the National Institute of Mental
Health, Rockville, Md; the Charles A. Dana Foundation, New York, NY; the National
Alliance for Research on Schizophrenia and Depression, Great Neck, NY (Dr
Simpson); the Ted and Varda Stanley Foundation, Arlington, Va; and contributors
to the Affective Disorders Fund and the George Browne Laboratory Fund at The
Johns Hopkins Hospital.
This study was presented as a poster at the 1995 World Congress of Psychiatric
Genetics, Cardiff, Wales, August 30, 1995.
We thank the many research assistants, technicians, secretaries, and
medical students who have contributed their energies to this study. We also
thank the clinicians who referred families for study and the family volunteers
and individuals who volunteered, without whose collaboration this research
would not have been possible.
Corresponding author and reprints: Sylvia G. Simpson, MD, University
of Colorado Health Sciences Center, 4200 E Ninth Ave, Box C268-71, Denver,
CO 80262 (e-mail: sylvia.simpson{at}uchsc.edu).
From the Departments of Psychiatry and Behavioral Sciences at The Johns
Hopkins University, Baltimore, Md (Drs Simpson, McInnis, MacKinnon, Edwin,
and DePaulo); The University of Chicago, Chicago, Ill (Dr McMahon); and Tufts
University, Boston, Mass (Dr Folstein).
REFERENCES
| |
1. Andreasen NC, Grove WM, Shapiro RW, Keller MB, Hirschfeld RM, McDonald-Scott P. Reliability of lifetime diagnosis: a multicenter collaborative perspective. Arch Gen Psychiatry. 1981;38:400-405.
FREE FULL TEXT
2. Rice JP, Rochberg N, Endicott J, Lavori PW, Miller C. Stability of psychiatric diagnoses: an application to the affective
disorders. Arch Gen Psychiatry. 1992;49:824-830.
FREE FULL TEXT
3. DePaulo JR Jr, Simpson SG. Therapeutic and genetic prospects of an atypical affective disorder. J Clin Psychopharmacol. 1987;7(suppl 6):50S-54S.
4. Coryell W, Endicott J, Andreasen N, Keller M. Bipolar I, bipolar II, and nonbipolar major depression among the relatives
of affectively ill probands. Am J Psychiatry. 1985;142:817-821.
FREE FULL TEXT
5. Akiskal HS, Chen SE, Davis GC, Puzantian VR, Kashgarian M, Bolinger JM. Borderline: an adjective in search of a noun. J Clin Psychiatry. 1985;46:41-48.
ISI
| PUBMED
6. Dunner DL, Gershon ES, Goodwin FK. Heritable factors in the severity of affective illness. Biol Psychiatry. 1976;11:31-42.
ISI
| PUBMED
7. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr. A family study of schizoaffective, bipolar I, bipolar II, unipolar,
and normal control probands. Arch Gen Psychiatry. 1982;39:1157-1167.
FREE FULL TEXT
8. Endicott J, Nee J, Andreasen N, Clayton P, Keller M, Coryell W. Bipolar II. Combine or keep separate? J Affect Disord. 1985;8:17-28.
FULL TEXT
|
ISI
| PUBMED
9. Simpson SG, Folstein SE, Meyers DA, McMahon FJ, Brusco DM, DePaulo JR Jr. Bipolar II: the most common bipolar phenotype? Am J Psychiatry. 1993;150:901-903.
FREE FULL TEXT
10. Coryell W, Endicott J, Reich T, Andreasen N, Keller M. A family study of bipolar II disorder. Br J Psychiatry. 1984;145:49-54.
FREE FULL TEXT
11. Heun R, Maier W. The distinction of bipolar II disorder from bipolar I and recurrent
unipolar depression: results of a controlled family study. Acta Psychiatr Scand. 1993;87:279-284.
ISI
| PUBMED
12. DePaulo JR Jr, Simpson SG, Gayle JO, Folstein SE. Bipolar II disorder in six sisters. J Affect Disord. 1990;19:259-264.
PUBMED
13. Heun R, Maier W. Bipolar II disorders in six first-degree relatives. Biol Psychiatry. 1993;34:274-276.
PUBMED
14. Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry. 1978;35:837-844.
FREE FULL TEXT
15. Spitzer RL, Endicott J, Robins E. Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry. 1978;35:773-782.
FREE FULL TEXT
16. McMahon FJ, Simpson SG, McInnis MG, Badner JA, MacKinnon DF, DePaulo JR. Linkage of bipolar disorder to chromosome 18q and the validity of bipolar
II disorder. Arch Gen Psychiatry. 2001;58:1025-1031.
FREE FULL TEXT
17. Simpson SG, Folstein SE, Meyers DA, DePaulo JR. Assessment of lineality in bipolar I linkage studies. Am J Psychiatry. 1992;149:1660-1665.
FREE FULL TEXT
18. Leckman JF, Sholomskas D, Thompson W, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39:879-883.
FREE FULL TEXT
19. Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons; 1981.
20. SPSS Base 7.0 Applications Guide. Chicago, Ill: SPSS Inc; 1996.
21. Dunner DL, Tay LK. Diagnostic reliability of the history of hypomania in bipolar II patients
and patients with major depression. Compr Psychiatry. 1993;34:303-307.
FULL TEXT
|
ISI
| PUBMED
22. Mazure C, Gershon ES. Blindness and reliability in lifetime psychiatric diagnoses. Arch Gen Psychiatry. 1979;36:521-525.
FREE FULL TEXT
23. Rice JP, McDonald-Scott P, Endicott J, Coryell W, Grove WM, Keller MB, Altis D. The stability of diagnosis with an application to bipolar II disorder. Psychiatry Res. 1986;19:285-296.
FULL TEXT
|
ISI
| PUBMED
24. Maziade M, Roy MA, Fournier JP, Cliche D, Merette C, Caron C, Garneau Y, Montgrain N, Shriqui C, Dion C, Nicole L, Potvin A, Lavallee JC, Pires A, Raymond V. Reliability of best-estimate diagnosis in genetic linkage studies of
major psychoses: results from the Quebec pedigree studies. Am J Psychiatry. 1992;149:1674-1686.
FREE FULL TEXT
25. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition. Washington, DC: American Psychiatric Association; 1994.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Association Study of Wnt Signaling Pathway Genes in Bipolar Disorder
Zandi et al.
Arch Gen Psychiatry 2008;65:785-793.
ABSTRACT
| FULL TEXT
What Is Familial About Familial Bipolar Disorder?: Resemblance Among Relatives Across a Broad Spectrum of Phenotypic Characteristics
Schulze et al.
Arch Gen Psychiatry 2006;63:1368-1376.
ABSTRACT
| FULL TEXT
Familial Variation in Episode Frequency in Bipolar Affective Disorder
Fisfalen et al.
Am. J. Psychiatry 2005;162:1266-1272.
ABSTRACT
| FULL TEXT
Impact of childhood abuse on the clinical course of bipolar disorder
GARNO et al.
Br. J. Psychiatry 2005;186:121-125.
ABSTRACT
| FULL TEXT
|
