[Note that research conducted prior to 2002 is not included on this page.]
Diagnosis of bipolar disorders: focus on bipolar disorder I and
bipolar disorder II.
MedGenMed. 2002 Aug 16;4(3):17.
disorders are currently divided into 4 entities: bipolar I, bipolar II, cyclothymic
disorder, and bipolar disorder not otherwise specified, as described in the fourth
edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
These subtypes of bipolar disorders cover a spectrum of severities, frequencies,
and durations of manic and depressive symptoms. The differential diagnosis among
these and with regard to other disorders with similar symptom features remains
the foundation for treatment of bipolar disorders. It is clear that much diversity
exists within these major subtypes, such that designations like "rapid cycling"
and "bipolar III" are being put forward and probed for clinical relevance.
Some of the concerns and advantages of including these less-established manifestations
of bipolar disorders in our diagnostic thinking are discussed here, and the utility
and drawbacks of our current diagnostic protocols are considered." [Full
Judd LL, Akiskal HS, Schettler PJ, Coryell
W, Maser J, Rice JA, Solomon DA, Keller MB.
The comparative clinical
phenotype and long term longitudinal episode course of bipolar I and II: a clinical
spectrum or distinct disorders?
J Affect Disord. 2003 Jan;73(1-2):19-32.
The present analyses were designed to compare the clinical characteristics and
long-term episode course of Bipolar-I and Bipolar-II patients in order to help
clarify the relationship between these disorders and to test the bipolar spectrum
hypothesis. METHODS: The patient sample consisted of 135 definite RDC Bipolar-I
(BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative
Depression Study (CDS) between 1978 and 1981; and were followed systematically
for up to 20 years. Groups were compared on demographic and clinical characteristics
at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets
of patients were compared on the number and type of affective episodes and the
duration of inter-episode well intervals observed during a 10-year period following
their resolution of the intake affective episode. RESULTS: BP-I and BP-II had
similar demographic characteristics and ages of onset of their first affective
episode. Both disorders had more lifetime comorbid substance abuse disorders than
the general population. BP-II had a significantly higher lifetime prevalence of
anxiety disorders in general, and social and simple phobias in particular, compared
to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II
patietns had a substantially more chronic course, with significantly more major
and minor depressive episodes and shorter inter-episode well intervals. BP-II
patients were prescribed somatic treatment a substantially lower percentage of
time during and between affective episodes. LIMITATIONS: BP-I patients with severe
manic course are less likely to be retained in long-term follow-up, whereas the
reverse might be true for BP-II patients who are significantly more prone to depression
(i.e., patients with less inclination to depression and with good prognosis may
have dropped out in greater proportions); this could increase the gap in long
term course characteristics between the two samples. The greater chronicity of
BP-II may be due, in part, to the fact that the patients were prescribed somatic
treatments substantially less often both during and between affective episodes.
CONCLUSIONS: The variety in severity of the affective episodes shows that bipolar
disorders, similar to unipolar disorders, are expressed longitudinally during
their course as a dimensional illness. The similarities of the clinical phenotypes
of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease
spectrum. They are, however, sufficiently distinct in terms of long-term course
(i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly
depressive course), that they are best classified as two separate subtypes in
the official classification systems." [Abstract]
LL, Schettler PJ, Akiskal HS, Maser J, Coryell W, Solomon D, Endicott J, Keller
Long-term symptomatic status of bipolar I vs. bipolar II disorders.
J Neuropsychopharmacol. 2003 Jun;6(2):127-137.
"Weekly affective symptom
severity and polarity were compared in 135 bipolar I (BP I) and 71 bipolar II
(BP II) patients during up to 20 yr of prospective symptomatic follow-up. The
course of BP I and BP II was chronic; patients were symptomatic approximately
half of all follow-up weeks (BP I 46.6% and BP II 55.8% of weeks). Most bipolar
disorder research has concentrated on episodes of MDD and mania and yet minor
and subsyndromal symptoms are three times more common during the long-term course.
Weeks with depressive symptoms predominated over manichypomanic symptoms in both
disorders (31) in BP I and BP II at 371 in a largely depressive course (depressive
symptoms=59.1% of weeks vs. hypomanic=1.9% of weeks). BP I patients had more weeks
of cyclingmixed polarity, hypomanic and subsyndromal hypomanic symptoms. Weekly
symptom severity and polarity fluctuated frequently within the same bipolar patient,
in which the longitudinal symptomatic expression of BP I and BP II is dimensional
in nature involving all levels of affective symptom severity of mania and depression.
Although BP I is more severe, BP II with its intensely chronic depressive features
is not simply the lesser of the bipolar disorders; it is also a serious illness,
more so than previously thought (for instance, as described in DSM-IV and ICP-10).
It is likely that this conventional view is the reason why BP II patients were
prescribed pharmacological treatments significantly less often when acutely symptomatic
and during intervals between episodes. Taken together with previous research by
us on the long-term structure of unipolar depression, we submit that the thrust
of our work during the past decade supports classic notions of a broader affective
disorder spectrum, bringing bipolarity and recurrent unipolarity closer together.
However the genetic variation underlying such a putative spectrum remains to be
A, Mandelli L, Lattuada E, Cusin C, Smeraldi E.
Clinical and demographic
features of mood disorder subtypes.
Psychiatry Res. 2002
"The aim of this study was to investigate demographic,
clinical and symptomatologic features of the following mood disorder subtypes:
bipolar disorder I (BP-I); bipolar disorder II (BP-II); major depressive disorder,
recurrent (MDR); and major depressive episode, single episode (MDSE). A total
of 1832 patients with mood disorders (BP-I=863, BP-II=141, MDR=708, and MDSE=120)
were included in our study. The patients were assessed using structured diagnostic
interviews and the operational criteria for psychotic illness checklist (n=885),
the Hamilton depression rating scale (n=167), and the social adjustment scale
(n=305). The BP-I patients were younger; had more hospital admissions; presented
a more severe form of symptomatology in terms of psychotic symptoms, disorganization,
and atypical features; and showed less insight into their disorder than patients
in the other groups. Compared with the major depressive subgroups, BP-I patients
were more likely to have an earlier age at onset, an earlier first lifetime psychiatric
treatment, and a greater number of illness episodes. BP-II patients had a higher
suicide risk than both BP-I and MDSE patients. MDSE patients presented less severe
symptomatology, lower age at observation, and a higher number of males. The retrospective
approach and the selection constraints due to the inclusion criteria are the main
limitations of the study. Our data support the view that BP-I disorder is quite
different from the remaining mood disorders from a demographic and clinical perspective,
with BP-II disorder having an intermediate position to MDR and MDSE, that is,
as a less severe disorder. This finding may help in the search for the biological
basis of mood disorders." [Abstract]
Clinical differences between bipolar II depression and unipolar
major depressive disorder: lack of an effect of age.
Disord. 2003 Jul;75(2):191-5.
"BACKGROUND: Inconsistent clinical differences
were reported in bipolar II versus unipolar depression. Age difference may be
a confounding factor. Study aims were to describe the clinical and family history
features of bipolar II versus unipolar depression, and to control for the possible
confounding effect of age on clinical features. METHODS: Consecutive 126 unipolar
and 187 bipolar II major depressive episode (MDE) outpatients were interviewed
with the Structured Clinical Interview for DSM-IV. Variables studied were gender,
age, age of onset, MDE recurrences, axis I comorbidity, MDE severity, psychotic,
melancholic, and atypical features, depression chronicity, melancholic, atypical,
and hypomanic symptoms, depressive mixed state-DMX3 (MDE+three or more concurrent
hypomanic symptoms), and mood disorders family history. The effect of age on clinical
differences was controlled by logistic regression (by adding age as an independent
variable after each independent variable). RESULTS: Bipolar II had significantly
lower age, lower age of onset, more recurrences, more atypical features, more
DMX3, more family history of bipolar II and MDE. Almost all the clinical differences
found significant in the first analysis resulted still significant when controlled
for age. LIMITATIONS: Single interviewer, non-blind, cross-sectional assessment,
bipolar II diagnosis based on history. CONCLUSIONS: Results confirmed previous
findings, and showed that bipolar II-unipolar MDE clinical differences were not
related to age." [Abstract]
S, Borgherini G, Conforti D, Scarso C, Magni G.
Depression in inpatients:
bipolar vs unipolar.
Psychol Rep. 2003 Jun;92(3 Pt 1):1031-9.
depressed inpatients were divided into three diagnostic groups to compare patterns
of sociodemographic characteristics, psychopathology, and psychosocial: 35 had
a single episode of major depression, 96 had recurrent major depression, and 31
had a bipolar disorder. Psychopathology and psychosocial functioning were measured
by clinician-rated scales, Montgomery-Asberg Depression Rating Scale, Hamilton
Rating Scale for Depression, Clinical Global Impression, and self-rating scales,
Symptom Checklist-90, Social Support Questionnaire, Social Adjustment Scale. The
three groups were comparable on sociodemographic variables, with the exception
of education. Univariate analyses showed a similar social impairment as measured
by Social Support Questionnaire, Social Adjustment Scale, and no significant differences
were recorded for the psychopathology when the total test scores (Montgomery-Asberg
Depression Rating Scale, Hamilton Rating Scale for Depression, Clinical Global
Index, Symptom Checklist-90) were evaluated. Some differences emerged for single
items in the Montgomery-Asberg Depression Rating Scale and Symptom Checklist-90.
These findings suggest a substantial similarity among the three groups. Results
are discussed in terms of the clinical similarities between unipolar and bipolar
patients during a depressive episode as well as the limitations of cross-sectional
study implies." [Abstract]
Bipolar II disorder and major depressive disorder: continuity
World J Biol Psychiatry. 2003 Oct;4(4):166-71.
To find if bipolar II disorder (BPII) and major depressive disorder (MDD) were
distinct categories or overlapping syndromes. METHODS: 308 BPII and 236 MDD outpatients,
presenting for major depressive episode (MDE) treatment, were interviewed with
the Structured Clinical Interview for DSM-IV. History of mania and hypomania,
and hypomanic symptoms present during MDE, were systematically investigated. Presence
of zones of rarity between BPII and MDD depressive syndromes was assessed. Atypical
and hypomanic symptoms were chosen because atypical features and depressive mixed
state (ie, MDE plus more than 2 concurrent hypomanic symptoms, according to Akiskal
and Benazzi 2003) were often reported to distinguish BPII from MDD depressive
syndromes (more common in BPII). If BPII were a distinct category, distributions
of these symptoms should show zones of rarity between BPII and MDD depressive
syndromes. Histograms and Kernel density estimate were used to study distributions
of these symptoms. RESULTS: BPII had significantly more atypical features and
depressive mixed state than MDD. Histograms and Kernel density estimate curves
of distributions of atypical and hypomanic symptoms in the entire sample did not
show zones of rarity. CONCLUSIONS: Finding no zones of rarity supports a continuity
between BPII and MDD (meaning partly overlapping disorders without clear boundaries)."
Bipolar II versus unipolar
chronic depression: a 312-case study.
"Differences between bipolar II depression
and unipolar depression have been reported, such as a lower age at onset and more
atypical features in bipolar II depression. The aim of the present study was to
compare chronic/nonchronic bipolar II depression with chronic/nonchronic unipolar
depression to determine whether the reported differences are present when chronicity
is taken into account. Three hundred twelve outpatients in a bipolar II/unipolar
major depressive episode were assessed with the Structured Clinical Interview
for DSM-IV-Clinician Version (SCID-CV), the Montgomery and Asberg Depression Rating
Scale (MADRS), and the Global Assessment of Functioning (GAF) Scale. No significant
difference was found between chronic bipolar II and chronic unipolar depression
(age at intake and onset, gender, duration of illness, recurrences, psychosis,
atypical features, axis I comorbidity, and severity). A significantly lower age
at onset and more atypical features were observed when comparing chronic/nonchronic
bipolar II with nonchronic unipolar depression. These findings suggest that differences
reported between bipolar II and unipolar depression are mainly due to nonchronic
unipolar depression. Chronic unipolar depression may be a subtype intermediate
between bipolar II depression and nonchronic unipolar depression." [Abstract]
S, Gex-Fabry M, Dayer A, Pardos ER, Roth L, Aubry JM, Bertschy G.
Retrospective Comparison of Inpatients with Mixed and Pure Depression.
2003 [Epub ahead of print]. Epub 2003 Nov 27.
"Some authors advocate a
broadening of the narrow concept of mixed episodes in the direction of mania leading
to the concept of mixed mania, and in the direction of depression leading to the
concept of mixed depression. The latter has been little investigated so far. In
the present article, we retrospectively compare 49 patients with pure depression
with 51 patients with mixed depression in terms of socio-demographic and clinical
variables in order to contribute to the validation of the distinction between
mixed and pure depression. Supporting this distinction, we observed that mixed
depressive patients more frequently had past histories of bipolar disorder and
alcohol abuse and had longer durations of hospital stay. These last two points
remain significant even when we control for the effect of the association with
J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rossler W.
Toward a re-definition
of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II,
minor bipolar disorders and hypomania.
J Affect Disord.
"BACKGROUND: The boundaries of bipolarity have
been expanding over the past decade. Using a well characterized epidemiologic
cohort, in this paper our objectives were: (1). to test the diagnostic criteria
of DSM-IV hypomania, (2). to develop and validate criteria for the definition
of softer expressions of bipolar-II (BP-II) disorder and hypomania, (3). to demonstrate
the prevalence, clinical validity and comorbidity of the entire soft bipolar spectrum.
METHODS: Data on the continuum from normal to pathological mood and overactivity,
collected from a 20-year prospective community cohort study of young adults, were
used. Clinical validity was analysed by family history, course and clinical characteristics,
including the association with depression and substance abuse. RESULTS: (1). Just
as euphoria and irritability, symptoms of overactivity should be included in the
stem criterion of hypomania; episode length should probably not be a criterion
for defining hypomania as long as three of seven signs and symptoms are present,
and a change in functioning should remain obligatory for a rigorous diagnosis.
(2). Below that threshold, 'hypomanic symptoms only' associated with major or
mild depression are important indicators of bipolarity. (3). A broad definition
of bipolar-II disorder gives a cumulative prevalence rate of 10.9%, compared to
11.4% for broadly defined major depression. A special group of minor bipolar disorder
(prevalence 9.4%) was identified, of whom 2.0% were cyclothymic; pure hypomania
occurred in 3.3%. The total prevalence of the soft bipolar spectrum was 23.7%,
comparable to that (24.6%) for the entire depressive spectrum (including dysthymia,
minor and recurrent brief depression). LIMITATION: A national cohort with a larger
number of subjects is needed to verify the numerical composition of the softest
bipolar subgroups proposed herein. CONCLUSION: The diagnostic criteria of hypomania
need revision. On the basis of its demonstrated clinical validity, a broader concept
of soft bipolarity is proposed, of which nearly 11% constitutes the spectrum of
bipolar disorders proper, and another 13% probably represent the softest expression
of bipolarity intermediate between bipolar disorder and normality." [Abstract]
Benazzi F, Akiskal HS.
The dual factor
structure of self-rated MDQ hypomania: energized-activity versus irritable-thought
J Affect Disord. 2003 Jan;73(1-2):59-64.
Bipolar II is diagnosed in a clinically depressed patient by documenting history
of hypomania. Therefore, it is of great significance for both clinical and research
purposes to characterize the factor structure of hypomania. METHODS: Among consecutive
depressive outpatients-126 major depressives and 187 bipolar II-diagnosed by the
Structured Clinical Interview for DSM-IV (Clinician Version), 181 who had clinically
recovered from depression were administered the Mood Disorder Questionnaire (MDQ
of. Am. J. Psychiatry 157, 1873). The MDQ is a newly developed, psychometrically
validated self-report screening instrument for bipolar spectrum disorders. It
screens for lifetime history of manic/hypomanic symptoms by including yes/no items
covering all DSM-IV symptoms of mania/hypomania. The MDQ symptom interrelationships
were studied by principal component analysis with varimax rotation. RESULTS: Hypomanic
symptoms occurring in >50% were racing thoughts, increased energy and social
activity, and irritability. Factor analysis revealed two factors: 'Energized-Activity'
(eigenvalue=3.1) and 'Irritability-Racing Thoughts' (eigenvalue=1.5). LIMITATIONS:
Cross-sectional assessment. CONCLUSIONS: Self-assessment of past hypomanic symptoms
by patients, during clinical remission from depression, revealed two independent
hypomanic factors, neither of which comprised euphoria. Hypomanic behavior appears
to be more fundamental for the diagnosis of hypomania than elated mood accorded
priority in DSM-IV; of hypomanic moods, irritability had greater significance
than elation. It would appear that self-report of euphoria is less likely when
hypomanias are brief (>or=2 vs. >or=4 days). The main implication for busy
clinical practice is that energized activity and irritable mood associated with
racing thoughts represent the modal experiences of hypomania among bipolar II
outpatients; euphoria is neither sensitive, nor pathognomonic, in the diagnosis
of these patients. These conclusions accord with recommendations made many years
ago for the diagnosis of hypomania among cyclothymic patients [. Am. J. Psychiatry
134, 1227]." [Abstract]
HS, Azorin JM, Hantouche EG.
Proposed multidimensional structure
of mania: beyond the euphoric-dysphoric dichotomy.
Disord. 2003 Jan;73(1-2):7-18.
"BACKGROUND: Although the construct of
depression has been subjected to numerous factor analytic studies and phenomenological
subtypes of clinical relevance have been delineated, this is not the case for
mania. The few available studies have reported at least two factors, which consist
of euphoric versus dysphoric-hostile subtypes. Our objective was to replicate
and further enrich this literature. METHODS: In the EPIMAN French National Study
we systematically evaluated 104 DSM-IV hospitalized manic patients in four university
centers in different regions of France. Psychiatrists completed the Beigel-Murphy
Manic State Rating Scale (MSRS), as well as the HAM-D(17), affective temperament
scales, and the GAF Axis V from DSM-IV. Categorization of patients into pure versus
dysphoric mania was made on the basis of clinical diagnosis, independent from
psychometric measures. RESULTS: On principal component analysis of the MSRS, three
factors explained the largest variance: a global manic (23.3% variance), paranoid-hostile
(14.8% variance), and psychotic (9.1% variance). After varimax rotation, we obtained
seven independent factors: F1 Disinhibition-instability, F2 Paranoia-hostility,
F3 Deficit, F4 Grandiosity-psychosis, F5 Elation-euphoria, F6 Depression, and
F7 (Hyper)sexuality. We could not demonstrate significant correlations between
the individual factors and impaired functioning on GAF. However, depressive and,
to some extent, cyclothymic temperaments correlated with F6 Depression. Finally,
intergroup comparisons between pure versus dysphoric mania diagnosed clinically
showed high levels of F3 Deficit and F5 Elation in the pure, and of F6 Depression
in dysphoric, mania; F2 Paranoia-hostility did not discriminate these two clinical
forms of mania. LIMITATIONS: Although the present analyses on the Beigel-Murphy
represent the largest sample studied to date, they are still underpowered and
do not guarantee a stable factorial structure. Our findings are cross-sectional
and require prospective validation. CONCLUSIONS: Our data suggest that 'dysphoria'
as used in the literature to qualify mania is insufficiently precise, and is best
further specified as 'depressive' versus 'irritable.' Moreover, our data extend
the rich multidimensional phenomenology of mania beyond the existing literature:
we submit that disinhibition-instability (a core 'activation' component) can,
on the one hand, be associated with distinct emotional presentations (euphoric,
depressive, or irritable-hostile), as well as psychotic and deficit symptomatology
on the other." [Abstract]
Gonzalez-Pinto A, Ballesteros J, Aldama A, Perez
de Heredia JL, Gutierrez M, Mosquera F, Gonzalez-Pinto A.
components of mania.
J Affect Disord. 2003 Sep;76(1-3):95-102.
An alternative to the categorical classification of psychiatric diseases is the
dimensional study of the signs and symptoms of psychiatric syndromes. To date,
there have been few reports about the dimensions of mania, and the existence of
a depressive dimension in mania remains controversial. The aim of this study was
to investigate the dimensions of manic disorder by using classical scales to study
the signs and symptoms of affective disorders. METHODS: One-hundred and three
consecutively admitted inpatients who met DSM IV criteria for bipolar disorder,
manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton
Depression Rating Scale (HDRS-21). A principal components factor analysis of the
HDRS-21 and the YMRS was carried out. RESULTS: Factor analysis showed five independent
and clinically interpretable factors corresponding to depression, dysphoria, hedonism,
psychosis and activation. The distribution of factor scores on the depressive
factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation
factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS:
Patients of the sample were all medicated inpatients. CONCLUSIONS: Mania seems
to be composed of three core dimensions, i.e. hedonism, dysphoria and activation,
and is frequently accompanied by a psychotic and a depressive factor. The existence
of a depressive factor suggests that it is essential to evaluate depression during
mania, and the distribution of the depressive factor supports the existence of
two different states in mania." [Abstract]
Meyer TD, Hautzinger M.
of affective symptoms in a sample of young adults.
Psychiatry. 2003 Mar-Apr;44(2):110-6.
"Symptoms of bipolar disorders include
depression and mania. The term "bipolar" implies states that are opposite
to each other. Construing scales that define mania and depression as opposite
ends of one dimension cannot account for the existence of mixed symptoms. One
self-report instrument, the Internal State Scale (ISS), combines both dimensions
in one measure. However, the ISS only assesses internal subjective states and
does not tap other typical and more objective symptoms of (hypo-) mania. To explore
the factorial structure of affective symptoms in a general population sample,
we extended the Center for Epidemiologic Studies-Depression Scale (CES-D), adding
items to assess manic symptoms as described in DSM-IV. The scale was completed
by 2,059 young adults. The results for the original CES-D are comparable to prior
studies. Factor-analysis for the extended CES-D revealed two factors in women
and men: most manic symptoms loaded high on a factor "euphoria-activation,"
whereas the other factor included all typical dysphoric-depressive symptoms, but
also included the "manic symptoms" of distractibility and irritability.
Our results support a two-factor model of bipolar symptoms in the general population
with irritability being more closely associated with dysphoria than euphoria.
The implications and limitations of the present results are discussed." [Abstract]
F, Akiskal HS.
Refining the evaluation of bipolar II: beyond the
strict SCID-CV guidelines for hypomania.
J Affect Disord.
"BACKGROUND: The prevalence of bipolar II disorder
in depressed outpatients is much higher than previously reported, a finding probably
related to systematic probing for past hypomania by trained clinicians. Our objective
was to further refine the strict SCID-CV guidelines for hypomania in depressed
outpatients. METHODS: 168 consecutive outpatients presenting with major depression
were systematically interviewed with the SCID-CV about all past hypomanic behavior,
irrespective of duration and initial negative response to the screening question
on mood. Once typical hypomanic behaviors were elicited, the patient was re-questioned
about mood change. RESULTS: The prevalence of bipolar II was 61.3%. Bipolar II,
so-defined, was indistinguishable at age of onset, recurrence, and atypical features
from a previous sample of 251 BP-II patients interviewed by the same clinician
(FB) without the present modification of the stem question on mood, and which
had yielded a prevalence of 45% in the same outpatient clinic. LIMITATIONS: Single
interviewer, and cross-sectional assessment. CONCLUSIONS: Systematic probing for
all past hypomanic symptoms and behaviors, independently of the answer to the
screening question on mood, can elicit hypomanic features that would otherwise
be discarded by strict adherence to the SCID-CV. A net gain of 16% in the diagnosis
of BP-II can thereby be achieved." [Abstract]
DA, Leon AC, Endicott J, Coryell WH, Mueller TI, Posternak MA, Keller MB.
mania over the course of a 20-year follow-up study.
Psychiatry. 2003 Nov;160(11):2049-51.
"OBJECTIVE: Using data from a longitudinal
study of the mood disorders, the investigators address the phenomenon of unipolar
mania. METHOD: Subjects diagnosed as having Research Diagnostic Criteria mania
at intake into the study were prospectively followed for up to 20 years. RESULTS:
Twenty-seven subjects had the diagnosis of unipolar mania at the time they entered
the study and had no history of major depression before enrolling in the study.
Seven of these subjects did not suffer any episodes of major depression during
the 15- to 20-year follow-up. CONCLUSIONS: These data support the diagnostic validity
of unipolar mania." [Abstract]
Yazici O, Kora K, Ucok A, Saylan M, Ozdemir O, Kiziltan
E, Ozpulat T.
Unipolar mania: a distinct disorder?
Affect Disord. 2002 Sep;71(1-3):97-103.
"BACKGROUND: This study aimed
to identify the differences between unipolar mania and classical bipolar disorder.
METHODS: Patients with at least four manic episodes and at least 4 years of follow-up
without any depressive episodes were classified as unipolar mania. This group
was compared to other bipolar-I patients defined according to DSM-IV regarding
their clinical and socio-demographic variables. RESULTS: The rate for unipolar
mania as defined by the study criteria was found to be 16.3% in the whole group
of bipolar-I patients. Unipolar manic patients tended to have more psychotic features
and be less responsive to lithium prophylaxis compared to other bipolar-I patients.
LIMITATIONS: Because it was a retrospective study, there may be some minor depressive
episodes left unrecorded in the unipolar mania group despite careful and thorough
investigation. In addition, even with our fairly strict criteria for the diagnosis
of unipolar mania, the possibility of a future depressive episode cannot be excluded.
CONCLUSIONS: Unipolar mania may be the presentation of a nosologically distinct
HS, Hantouche EG, Allilaire JF, Sechter D, Bourgeois ML, Azorin JM, Chatenet-Duchene
L, Lancrenon S.
Validating antidepressant-associated hypomania (bipolar
III): a systematic comparison with spontaneous hypomania (bipolar II).
Affect Disord. 2003 Jan;73(1-2):65-74.
"BACKGROUND: According to DSM-IV
and ICD-10, hypomania which occurs solely during antidepressant treatment does
not belong to the category of bipolar II (BP-II). METHODS: As part of the EPIDEP
National Multisite French Study of 493 consecutive DSM-IV major depressive patients
evaluated in at least two semi-structured interviews 1 month apart, 144 (29.2%)
fulfilled the criteria for bipolar II with spontaneous hypomania (BP-II Sp), and
52 (10.5%) had hypomania associated solely with antidepressants (BP-H AA). RESULTS:
BP-II Sp group had earlier age at onset, more hypomanic episodes, and higher ratings
on cyclothymic and hyperthymic temperaments, and abused alcohol more often. The
two groups were indistinguishable on the hypomania checklist score (12.2+/-4.0
vs. 11.4+/-4.4, respectively, P=0.25) and on rates of familial bipolarity (14.1%
vs. 11.8%, respectively, P=0.68). But BP-H AA had significantly more family history
of suicide, had higher ratings on depressive temperament, with greater chronicity
of depression, were more likely to be admitted to the hospital for suicidal depressions,
and were more likely to have psychotic features; finally, clinicians were more
likely to treat them with ECT, lithium and mood stabilizing anticonvulsants. LIMITATION:
Naturalistic study, where treatment was uncontrolled. CONCLUSION: BP-H AA emerges
as a disorder with depressive temperamental instability, manifesting hypomania
later in life (and, by definition, during pharmacotherapy only). By the standards
of clinicians who have taken care of these patients for long periods of time,
BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit
that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion
within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone
phenotype of this disorder, and which is susceptible to destabilization under
antidepressant treatment. These considerations argue for revisions of DSM-IV and
ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression
of BP-II; phenotypically; it might provisionally be categorized as bipolar III."
TD, Keller F.
Is there evidence for a latent class called 'hypomanic
J Affect Disord. 2003 Aug;75(3):259-67.
Affective disorders belong to the most common psychiatric disorders. Several risk
factors have been postulated and empirically investigated. Researchers like Akiskal
[Interpersonal Factors in the Origin and Course of Affective Disorders, Gaskell,
London, 1996] have pointed out the associations between sub-affective temperaments
and affective disorders. However, no study has dealt with the issue whether there
is a latent class of such sub-affective temperaments or if such temperaments are
best conceptualized as fully dimensional. We investigated whether the Hypomanic
Personality Scale [J. Abnorm. Psychol. 121 (1986) 214-222] as an indicator of
hyperthymia is taxonic in structure. METHODS: We chose two different samples to
address this issue: A sample of young adults (n = 1,966) and another sample of
adolescents (n = 4,045). We ran MAXCOV-HITMAX analyses based on identical subsets
of items in both samples. RESULTS: Neither in the sample of young adults nor in
the sample of adolescents there was evidence for a latent class called 'hypomanic
temperament'. LIMITATION: Only one indicator for vulnerability and one procedure
to test for latent classes was used. Furthermore, we do not know how many of our
sample had a life-time history or current affective disorders. CONCLUSIONS: The
hypomanic-hyperthymic temperament is best conceptualized as a dimension in the
general population. However, before drawing final conclusions about the taxonicity
of the risk for affective disorders, more research is needed using different measures,
samples and methods to resolve this question of the dimensionality of vulnerability.
Additionally, the question remains open how to conceptualize mania itself."
LL, Gitlin MJ, Mintz J, Leight KL, Frye MA.
is associated with functional impairment in patients with bipolar disorder.
Clin Psychiatry. 2002 Sep;63(9):807-11.
"BACKGROUND: The purpose of this
study was to assess whether a relationship exists between mild depressive symptoms
and overall functioning in subjects with bipolar disorder. METHOD: Twenty-five
male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced
a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined
using the Structured Clinical Interview for DSM-III-R, were evaluated for degree
of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D)
and for overall functional status using the Global Assessment of Functioning (GAF,
DSM-IV Axis V). RESULTS: GAF scores were significantly negatively correlated with
HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient
had a HAM-D score high enough to be considered clinically depressed. CONCLUSION:
The results of this study support a relationship between subsyndromal depressive
symptoms and functional impairment in bipolar subjects, despite their not meeting
threshold criteria for a major depressive episode. These findings raise the possibility
that in some patients with bipolar disorder subsyndromal depressive symptoms might
contribute to ongoing functional impairment." [Abstract]
HU, Mhlig S, Pezawas L.
Natural course and burden of bipolar disorders
This paper is a revised version of a presentation held at the CINP International
Workshop, St Tropez, France, 36 September 2001.
Int J Neuropsychopharmacol.
"Despite an abundance of older and more recent retrospective
and considerably fewer prospective-longitudinal studies in bipolar disorders I
and II, there are still remarkable deficits with regard to our knowledge about
the natural course and burden. The considerable general and diagnosis-specific
challenges posed by the nature of bipolar disorders are specified, highlighting
in particular problems in diagnostic and symptom assessment, shifts in diagnostic
conventions and the broadening of the diagnostic concept by including bipolar
spectrum disorders. As a consequence it still remains difficult to agree on several
core features of bipolar disorders, such as when they begin, how many remit spontaneously
and how many take a chronic course. On the basis of clinical and epidemiological
findings this paper summarizes (i) a significant need to extend the study of the
natural course of bipolar disorder in clinical samples beyond the snapshot of
acute episodes to the study of the mid-term and long-term symptom course, associated
comorbidities and the associated burden of the disease. (ii) In terms of epidemiological
studies, that are also of key importance for resolving the critical issues of
threshold definitions in the context of the bipolar spectrum concept, there is
a clear need for identifying the most relevant risk factors for the first onset
and those for the further illness progression in early stages. Since there are
some indications that these critical processes might start as early as adolescence,
such studies might concentrate on young cohorts and clearly before these prospective
patients come to clinical attention. (iii) The value of both types of studies
might be enhanced, if beyond the use of standardized diagnostic interview, special
attempts are made to use prospective life- and episode-charting methods for bipolar
Statistical methods for longitudinal research on bipolar disorders.
Disord. 2003 Jun;5(3):156-68.
"OBJECTIVES: Outcomes research in bipolar
disorders, because of complex clinical variation over-time, offers demanding research
design and statistical challenges. Longitudinal studies involving relatively large
samples, with outcome measures obtained repeatedly over-time, are required. In
this report, statistical methods appropriate for such research are reviewed. METHODS:
Analytic methods appropriate for repeated measures data include: (i) endpoint
analysis; (ii) endpoint analysis with last observation carried forward; (iii)
summary statistic methods yielding one summary measure per subject; (iv) random
effects and generalized estimating equation (GEE) regression modeling methods;
and (v) time-to-event survival analyses. RESULTS: Use and limitations of these
several methods are illustrated within a randomly selected (33%) subset of data
obtained in two recently completed randomized, double blind studies on acute mania.
Outcome measures obtained repeatedly over 3 or 4 weeks of blinded treatment in
active drug and placebo sub-groups included change-from-baseline Young Mania Rating
Scale (YMRS) scores (continuous measure) and achievement of a clinical response
criterion (50% YMRS reduction). Four of the methods reviewed are especially suitable
for use with these repeated measures data: (i) the summary statistic method; (ii)
random/mixed effects modeling; (iii) GEE regression modeling; and (iv) survival
analysis. CONCLUSIONS: Outcome studies in bipolar illness ideally should be longitudinal
in orientation, obtain outcomes data frequently over extended times, and employ
large study samples. Missing data problems can be expected, and data analytic
methods must accommodate missingness." [Abstract]
LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon
AC, Keller MB.
A prospective investigation of the natural history
of the long-term weekly symptomatic status of bipolar II disorder.
Gen Psychiatry. 2003 Mar;60(3):261-9.
"BACKGROUND: This is the first prospective
longitudinal study, to our knowledge, of the natural history of the weekly symptomatic
status of bipolar II disorder (BP-II). METHODS: Weekly affective symptom status
ratings for 86 patients with BP-II were based on interviews conducted at 6- or
12-month intervals during a mean of 13.4 years of prospective follow-up. Percentage
of weeks at each symptom severity level and the number of shifts in symptom status
and polarity were examined. Predictors of chronicity for BP-II were evaluated
using new chronicity measures. Chronicity was also analyzed in relation to the
percentage of follow-up weeks with different types of somatic treatment. RESULTS:
Patients with BP-II were symptomatic 53.9% of all follow-up weeks: depressive
symptoms (50.3% of weeks) dominated the course over hypomanic (1.3% of weeks)
and cycling/mixed (2.3% of weeks) symptoms. Subsyndromal, minor depressive, and
hypomanic symptoms combined were 3 times more common than major depressive symptoms.
Longer intake episodes, a family history of affective disorders, and poor previous
social functioning predicted greater chronicity. Prescribed somatic treatment
did not correlate significantly with symptom chronicity. Patients with BP-II of
brief (2-6 days) vs longer (> or =7 days) hypomanias were not significantly
different on any measure. CONCLUSIONS: The longitudinal symptomatic course of
BP-II is chronic and is dominated by depressive rather than hypomanic or cycling/mixed
symptoms. Symptom severity fluctuates frequently within the same patient over
time, involving primarily symptoms of minor and subsyndromal severity. Longitudinally,
BP-II is expressed as a dimensional illness involving the full severity range
of depressive and hypomanic symptoms. Hypomania of long or short duration in BP-II
seems to be part of the same disease process." [Abstract]
RM, Denicoff KD, Leverich GS, Altshuler LL, Frye MA, Suppes TM, Rush AJ, Keck
PE Jr, McElroy SL, Luckenbaugh DA, Pollio C, Kupka R, Nolen WA.
in 258 bipolar outpatients followed for 1 year with daily prospective ratings
on the NIMH life chart method.
J Clin Psychiatry. 2003 Jun;64(6):680-90;
"BACKGROUND: A number of recent longitudinal outcome studies
have found substantial long-term morbidity in patients with bipolar disorder.
The detailed course and pattern of illness emerging despite comprehensive treatment
with mood stabilizers and adjunctive agents have previously not been well delineated.
METHOD: 258 consecutive outpatients admitted from 1996 to 1999 to the Stanley
Foundation Bipolar Network who had a full year of prospective daily clinician
ratings on the National Institute of Mental Health-Life Chart Method were included
in the analysis. Patients were diagnosed by the Structured Clinical Interview
for DSM-IV, with the majority (76%) having bipolar I disorder. They completed
a questionnaire on demographics and prior illness course, and variables associated
with outcome were examined in a hierarchical multinomial logistic regression analysis.
Patients were treated naturalistically with a mean of 4.1 psychotropic medications
during the year. RESULTS: Despite comprehensive pharmacologic treatment, mean
time depressed (33.2% of the year) was 3-fold higher than time manic (10.8%);
62.8% of patients had 4 or more mood episodes per year. Two thirds of the patients
were substantially impacted by their illness; 26.4% were ill for more than three
fourths of the year, and 40.7% were intermittently ill with major affective episodes.
After logistic regression analysis, those who were ill most of the year, compared
with the largely well group, had a significantly greater family history of substance
abuse, 10 or more depressive episodes, and limited occupational functioning prior
to Network entry. CONCLUSION: A majority of outpatients with bipolar illness,
even with intense monitoring and treatment in specialty clinics, have a considerable
degree of residual illness-related morbidity, including a 3-fold greater amount
of time spent depressed versus time spent manic. A personal or family history
of substance abuse, 10 or more prior depressions, and limited occupational functioning
predicted the poorest outcomes. Additional interventions, particularly those targeted
at treating depressive phases of bipolar illness, are greatly needed." [Abstract]
M, Zarate CA Jr, Hennen J, Khalsa HM, Strakowski SM, Gebre-Medhin P, Salvatore
P, Baldessarini RJ.
The McLean-Harvard First-Episode Mania Study:
prediction of recovery and first recurrence.
Am J Psychiatry.
"OBJECTIVE: Since improved prediction of illness
course early in bipolar disorder is required to guide treatment planning, the
authors evaluated recovery, first recurrence, and new illness onset following
first hospitalization for mania. METHOD: Bipolar disorder patients (N=166) were
followed 2-4 years after their first hospitalization for a manic or mixed episode
to assess timing and predictors of outcomes. Three aspects of recovery were measured:
syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania
Rating Scale score </=5 and Hamilton Depression Rating Scale score </=8),
and functional (regaining of premorbid occupational and residential status). Rates
of remission (syndromal recovery sustained >/=8 weeks), switching (onset of
new dissimilar illness before recovery), relapse (new episode of mania within
8 weeks of syndromal recovery), and recurrence (new episode postremission) were
also assessed. RESULTS: By 2 years, most subjects achieved syndromal recovery
(98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery.
Factors associated with a shorter time to syndromal recovery for 50% of the subjects
were female sex, shorter index hospitalization, and lower initial depression ratings.
Only 43% achieved functional recovery; these subjects were more often older and
had shorter index hospitalizations. Within 2 years of syndromal recovery, 40%
experienced a new episode of mania (20%) or depression (20%), and 19% switched
phases without recovery. Predictors of mania recurrence were initial mood-congruent
psychosis, lower premorbid occupational status, and initial manic presentation.
Predictors of depression onset were higher occupational status, initial mixed
presentation, and any comorbidity. Antidepressant treatment was marginally related
to longer time to recovery and earlier relapse. CONCLUSIONS: Within 2-4 years
of first lifetime hospitalization for mania, all but 2% of patients experienced
syndromal recovery, but 28% remained symptomatic, only 43% achieved functional
recovery, and 57% switched or had new illness episodes. Risks of new manic and
depressive episodes were similar but were predicted by contrasting factors."
Baldessarini RJ, Tondo L, Hennen J.
and previous episodes: relationships to pretreatment morbidity and response to
maintenance treatment in bipolar I and II disorders.
Disord. 2003 Jun;5(3):169-79.
"OBJECTIVE: To clarify relationships of
treatment delay and pretreatment episode count with pretreatment morbidity and
responses to maintenance treatments in bipolar disorders. METHODS: In 450 DSM-IV
bipolar I (n = 293) or II (n = 157) patients (280 women, 170 men), we evaluated
correlations of latency from illness-onset to starting maintenance treatment and
pretreatment episode counts with pretreatment morbidity and treatment response.
We considered morbidity measures before and during treatment, and their differences.
RESULTS: Latency averaged 7.8 years, with 9.0 episodes per patient, before various
maintenance treatments started. Morbidity (percentage of time-ill, episodes per
year, first wellness-interval, or proportion of subjects hospitalized or having
no recurrences) during maintenance treatment averaging 4.2 years was unrelated
to treatment latency or pretreatment episode count. However, pretreatment morbidity
was greater with shorter latency, resulting in larger relative reduction of morbidity
after earlier treatment. CONCLUSIONS: Greater treatment latency and pretreatment
episode count were not followed by greater morbidity during treatment, although
longer delay yielded smaller during-versus-before treatment reduction in morbidity.
Predictions that longer treatment delay or more pretreatment episodes lead to
poorer responses to various maintenance treatments in bipolar I or II disorder
were not supported." [Abstract]
C, Tondo L, Bratti IM, Bschor T, Bauer M, Viguera AC, Baldessarini RJ.
latency and outcome in bipolar disorders.
Can J Psychiatry.
"OBJECTIVE: To analyze new and reviewed findings
to evaluate relations between treatment response and latency from onset of bipolar
disorder (BD) to the start of mood-stabilizer prophylaxis. METHOD: We analyzed
our own new data and added findings from research reports identified by computerized
searching. RESULTS: We found 11 relevant studies, involving 1485 adult patients
diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years
(SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness
intensity and shorter treatment latency were closely associated, resulting in
a greater apparent reduction in morbidity with earlier treatment. However, this
finding was not sustained after correction for pretreatment morbidity, and treatment
latency did not predict morbidity during treatment. Therefore, assessments based
on improvement with treatment, or without correction for pretreatment morbidity,
can be misleading. CONCLUSIONS: Available evidence does not support the proposal
that delayed prophylaxis may limit response to prophylactic treatment in BD and
related disorders." [Abstract]
JF, Ernst CL.
associated with the delayed initiation of mood stabilizers at illness onset in
J Clin Psychiatry. 2002 Nov;63(11):985-91.
Whether delays in the initiation of appropriate pharmacotherapy for bipolar illness
negatively affect course, outcome, or lifetime suicide risk remains at issue.
METHOD: Lifetime affective syndromes and the initial emergence of affective symptoms
were assessed by lifecharting in 56 DSM-IV bipolar patients. Lifetime treatment
interventions were recorded by clinical interview with corroboration via record
reviews. Lag times to the initiation of a mood stabilizer (after initial symptom
onset and/or first lifetime affective episode) were assessed relative to functional
outcome and lifetime suicide attempts. RESULTS: Mean +/- SD lag time from initial
affective symptoms until first mood stabilizer treatment was 9.8 +/- 9.4 years.
A greater number of years from symptom onset to first mood stabilizer was associated
with poorer past year social functioning (r = -0.35, p =.008), more annual hospitalizations
(r = 0.38, p =.004), and a greater likelihood for making a lifetime suicide attempt
(odds ratio = 7.26, 95% confidence interval = 1.62 to 32.59; Wald chi2 = 6.69,
df = 1, p =.010). Delayed mood stabilizer initiation was linked with poorer outcomes
in these domains regardless of initial index episode polarities of mania versus
depression. Prolonged delays to bipolar diagnoses and mood stabilizer initiation
were associated with earlier ages at affective symptom onset (p <.03) and milder
severity of initial symptoms (p =.003). Psychotherapy initiation often preceded
mood stabilizer introduction by >/= 8 years. CONCLUSION: Delays in the initiation
of mood stabilizer pharmacotherapy at illness onset, even for relatively mild
symptoms at illness onset and regardless of index episode polarity, may confer
an elevated risk for suicidal behavior, poorer social adjustment, and more hospitalizations
in bipolar disorder. Greater surveillance screening for bipolar illness in patients
who first present for psychotherapy may help to diminish these adverse outcomes."
Ghaemi N, Sachs GS, Goodwin FK.
is to be done? Controversies in the diagnosis and treatment of manic-depressive
World J Biol Psychiatry. 2000 Apr;1(2):65-74.
In recent years, much progress has been made in the diagnosis and treatment of
schizophrenia and depression. Bipolar disorder, however, remains frequently misunderstood,
leading to inconsistent diagnosis and treatment. Why is the case? What is to be
done about it? METHODS: We critically review studies in the nosology of bipolar
disorder and the effects of antidepressant agents. RESULTS: Bipolar disorder is
underdiagnosed and frequently misdiagnosed as unipolar major depressive disorder.
Antidepressants are probably overused and mood stabilisers underused. Reasons
for underdiagnosis include patients' impaired insight into mania, failure to involve
family members in the diagnostic process, and inadequate understanding by clinicians
of manic symptoms. We propose using a mnemonic to aid in diagnosis, obtaining
family report, and utilising careful clinical interviewing techniques given the
limitations of patients' self-report. We recommend aggressive use of mood stabilisers,
and less emphasis on antidepressants. CONCLUSIONS: The state of diagnosis and
treatment in bipolar disorder is suboptimal. More diagnostic attention to manic
criteria is necessary and the current pattern of use of antidepressant use in
bipolar disorder needs to change." [Abstract]
Hirschfeld RM, Lewis L, Vornik LA.
and impact of bipolar disorder: how far have we really come? Results of the national
depressive and manic-depressive association 2000 survey of individuals with bipolar
J Clin Psychiatry. 2003 Feb;64(2):161-74.
To assess the experience of selected individuals living with bipolar disorder
and compare this experience with that of a similar group of individuals sampled
in 1992. METHOD: In June 2000, 4192 self-administered questionnaires were sent
to National Depressive and Manic-Depressive Association chapters for distribution
to support group participants diagnosed with bipolar disorder. By July 31, 2000,
the first 600 completed surveys were analyzed. RESULTS: Over one third of respondents
sought professional help within 1 year of the onset of symptoms. Unfortunately,
69% were misdiagnosed, with the most frequent misdiagnosis being unipolar depression.
Those who were misdiagnosed consulted a mean of 4 physicians prior to receiving
the correct diagnosis. Over one third waited 10 years or more before receiving
an accurate diagnosis. Despite having underreported manic symptoms, more than
half believe their physicians' lack of understanding of bipolar disorder prevented
a correct diagnosis from being made earlier. In 2000, the respondents reported
a greater negative impact of bipolar disorder on families, social relationships,
and employment than did the respondents in 1992. Overall, respondents were satisfied
with their current treatment, which often included medication, talk therapy, and
support groups. Respondents who were highly satisfied with their treatment provider
had a more positive outlook on their illness and their ability to cope with it.
CONCLUSION: Individuals with bipolar disorder reported that the illness manifests
itself early in life but that accurate diagnosis lags by many years. The illness
exacts great hardships on the individual and the family and has a profoundly negative
effect on careers. These findings are very similar to those reported nearly a
decade ago." [Abstract]
Validating 'hard' and 'soft'
phenotypes within the bipolar spectrum: continuity or discontinuity?
Affect Disord. 2003 Jan;73(1-2):1-5.
"The unitary Kraepelian concept of
manic-depressive illness which incorporated attenuated forms, personal dispositions
to mood instability, as well as much of the terrain of remitting depressions,
may be considered by many to be too broad. On the other hand, the presently preferred
unipolar-bipolar dichotomy in official nosology fails to account for the very
common occurrence of clinical and subclinical conditions in the interface of major
depressive disorders and bipolarity. The emerging concept of the bipolar spectrum
represents a provocative working hypothesis to account for these conditions."
Jackson A, Cavanagh J, Scott J.
review of manic and depressive prodromes.
J Affect Disord.
"BACKGROUND: This paper explores whether individuals
with a mood disorder can identify the nature and duration of depressive and manic
prodromes. METHODS: Seventy-three publications of prodromal symptoms in bipolar
and unipolar disorders were identified by computer searches of seven databases
(including MEDLINE and PsycLIT) supplemented by hand searches of journals. Seventeen
studies (total sample=1191 subjects) met criteria for inclusion in a systematic
review. RESULTS: At least 80% of individuals with a mood disorder can identify
one or more prodromal symptoms. There are limited data about unipolar disorders.
In bipolar disorders, early symptoms of mania are identified more frequently than
early symptoms of depression. The most robust early symptom of mania is sleep
disturbance (median prevalence 77%). Early symptoms of depression are inconsistent.
The mean length of manic prodromes (>20 days) was consistently reported to
be longer than depressive prodromes (<19 days). However, depressive prodromes
showed greater inter-individual variation (ranging from 2 to 365 days) in duration
than manic prodromes (1-120 days). LIMITATIONS: Few prospective studies of bipolar,
and particularly unipolar disorders have been reported. CONCLUSIONS: Early symptoms
of relapse in affective disorders can be identified. Explanations of the apparent
differences in the recognition and length of prodromes between mania and bipolar
depression are explored. Further research on duration, sequence of symptom appearance
and characteristics of prodromes is warranted to clarify the clinical usefulness
of early symptom monitoring." [Abstract]
C, Swendsen J, Van den Bulke D, Sorbara F, Demotes-Mainard J, Leboyer M.
hyper-reactivity as a fundamental mood characteristic of manic and mixed states.
Psychiatry. 2003 May;18(3):124-8.
"BACKGROUND: The relationship between
depression and mania remains poorly understood and is responsible for much of
the confusion about mixed states. The difficulty in conceptualizing opposite states
such as euphoric and depressive moods during the same episode may account for
the considerable differences in reported frequencies of mixed states, among acutely
manic patients. It is possible that the fundamental mood characteristic of mania
is not tonality of mood (e.g. euphoric, irritable or depressed mood), but rather
the intensity of emotions. METHOD: We interviewed 30 patients hospitalized for
a manic episode, asking about their symptoms during the episode, using the list
of symptoms for manic and depressive episode of the DSM-IV criteria. Emotional
hyper-reactivity, defined as an increase in the intensity of all emotions, was
assessed using the Hardy Scale. Manic symptoms were also assessed by a clinician
using the Beck-Rafaelsen Mania Scale. RESULTS: This study showed that most of
the manic episodes presented many dysphoric symptoms, more particularly depressive
mood (33%), irritability (53%), anxiety (76%), and recurrent thoughts of death
or suicidal ideation (33%). However, only 10% of our sample met the criteria for
mixed state. The other symptoms reported by patients and included in the DSM-IV
criteria for depressive mood are common between depressive and manic episodes.
All patients (100%) reported that they felt all their emotions with an unusual
intensity. CONCLUSION: We suggest that the most appropriate way to define mood
in manic states is as a function of intensity, and not as a function of tonality.
This definition circumvents the arbitrary dichotomy between mania and mixed state.
With this definition, manic episodes can be described as being more or less dysphoric,
with the actual characteristics of dysphoria encompassing irritability, anxiety,
or depressive affect. This point could be extremely helpful in discriminating
mixed state or dysphoric mania from depression." [Abstract]
I, Peeters F, Havermans R, Nicolson NA, DeVries MW, Delespaul P, Van Os J.
reactivity to daily life stress in psychosis and affective disorder: an experience
Acta Psychiatr Scand. 2003 Feb;107(2):124-31
To investigate the emotional reactivity to small disturbances in daily life in
patients with non-affective psychosis (NAP), bipolar disorder (BD) and major depression
[major depressive disorder (MDD)]. METHOD: Forty-two patients with NAP, 38 with
BD, 46 with MDD, and 49 healthy controls were studied with the experience sampling
method to assess (i) appraised subjective stress of small disturbances in daily
life and (ii) emotional reactivity, reflected in changes in positive affect (PA)
and negative affect (NA). RESULTS: Multilevel regression analyses showed an increase
in NA in MDD, a decrease in PA in BD and both an increase in NA and a decrease
in PA in NAP in association with the subjectively stressful situations, compared
with the control subjects. CONCLUSION: Individuals with NAP, MDD and BD display
differences in emotional stress reactivity. Type of mood disorder may exert a
pathoplastic effect on emotional reactivity in individuals with MDD and BD. Individuals
with NAP may be most vulnerable to the effects of daily life stress." [Abstract]
JB, Chiu YF, MacKinnon DF, Miller EB, Simpson SG, McMahon FJ, McInnis MG, DePaulo
Familial aggregation of psychotic symptoms in a replication
set of 69 bipolar disorder pedigrees.
Am J Med Genet. 2003
"We found evidence previously of familial aggregation
of psychotic symptoms in 65 bipolar disorder pedigrees. This finding, together
with prior evidence from clinical, family, neurobiological, and linkage studies,
suggested that psychotic bipolar disorder may delineate a valid subtype. We sought
to replicate this finding in 69 new bipolar disorder pedigrees. The presence of
psychotic symptoms, defined as hallucinations or delusions, during an affective
episode was compared in families of 46 psychotic and 23 non-psychotic bipolar
I probands ascertained at Johns Hopkins for the NIMH Bipolar Disorder Genetics
Initiative. There were 198 first-degree relatives with major affective disorder
including 90 with bipolar I disorder. Significantly more psychotic proband families
than non-psychotic proband families (76% vs. 48%) contained at least one affected
relative with psychotic symptoms. Psychotic symptoms occurred in 35% of relatives
of psychotic probands and in 22% of relatives of non-psychotic probands (P = 0.10).
Both psychotic affective disorder generally and psychotic bipolar I disorder clustered
significantly in families. These results are consistent with our prior report
although the magnitude of the predictive effect of a psychotic proband is less
in the replication families. Our findings provide modest support for the validity
of psychotic bipolar disorder as a subtype of bipolar disorder. This clinically
defined subtype may prove more homogeneous than the disorder as a whole at the
level of genetic etiology and of neuropathology/pathophysiology. Families with
this subtype should be used to search for susceptibility genes common to bipolar
disorder and schizophrenia, and for biological markers that may be shared with
M, Pirozzi R, Magliano L, Bartoli L.
Agitated depression in bipolar
I disorder: prevalence, phenomenology, and outcome.
Psychiatry. 2003 Dec;160(12):2134-40.
"OBJECTIVE: The study aimed to explore
how prevalent agitated depression is in bipolar I disorder, whether it represents
a mixed state, and whether it differs from nonagitated depression with respect
to course and outcome. METHOD: From 313 bipolar I patients with an index episode
of major depression, the authors selected those fulfilling Research Diagnostic
Criteria for agitated depression. These 61 patients were compared to 61 randomly
recruited bipolar I patients with an index episode of nonagitated depression and
61 randomly recruited bipolar I patients with an index episode of mania regarding
demographic, historical, and clinical features. The two depressive groups were
also compared regarding time to recovery from the index episode, treatment received
for that episode, percentage of time spent in an affective episode during a prospective
observation period, and 5-year outcome. RESULTS: Patients with agitated depression
were consistently not elated or grandiose, but one-fourth had the cluster of symptoms
with racing thoughts, pressured speech, and increased motor activity, and one-fourth
had the paranoia-aggression-irritability cluster. Compared to patients with nonagitated
depression, they had a longer time to 50% probability of recovery from the index
episode, were more likely to receive standard antipsychotic drugs during that
episode, and spent more time in an affective episode during the observation period.
CONCLUSIONS: The occurrence of agitated depression in bipolar I disorder is not
rare and has significant prognostic and therapeutic implications. Whether the
co-occurrence of a major depressive syndrome with one or two of these symptomatic
clusters makes up a "mixed state" remains unclear." [Abstract]
Benazzi F, Helmi S, Bland
Agitated depression: unipolar? Bipolar? Or both?
Clin Psychiatry. 2002 Jun;14(2):97-104.
"The classification of agitated
depression (major depressive episode (MDE) plus psychomotor agitation) in mood
disorders is unclear. DSM-IV is neutral on this point. As antidepressants may
increase agitation, a better understanding of agitated depression is important
for clinical practice. Study aim was to find if agitated depression was closer
to bipolar or to unipolar disorders, by studying its association with variables
typically related to bipolar disorders (early onset, many recurrences, more atypical
features, more bipolar family history), and by studying its association with bipolar
II disorder. Consecutive 151 unipolar and 226 bipolar II psychoactive drug-free
MDE outpatients were interviewed with the Structured Clinical Interview for DSM-IV,
when presenting for MDE treatment. Agitated MDE patients were compared with nonagitated
MDE patients. Statistics were t test for means, two-sample test of proportion,
and logistic regression (STATA 7). Agitated MDE was present in 85 patients (22.5%).
It had significantly more bipolar II disorder patients (80.0% vs. 54.1%, p = 0.0000),
more females, lower age at onset, longer duration of illness, more MDE recurrences,
more atypical features, more MDE symptoms, and more family history of bipolar
disorders, than nonagitated MDE. To control for the possible confounding effect
of bipolar II disorder, logistic regression was used. All the significant differences
became nonsignificant. Results might suggest that agitated MDE might be closer
to the bipolar spectrum than to unipolar disorder, because it was associated with
variables typically distinguishing bipolar from unipolar disorders, and with bipolar
II disorder. Further studies on this topic are needed." [Abstract]
Highly recurrent unipolar may be related to bipolar II.
Psychiatry. 2002 Jul-Aug;43(4):263-8.
"Unipolar and bipolar disorders
may be subgroups of a single mood disorder, of which the key feature is not polarity,
but the episodic, recurrent course. The aim of this study was to determine whether
highly recurrent unipolar was related to bipolar II, by comparing clinical and
family history features. Eighty-nine consecutive unipolar and 151 consecutive
bipolar II outpatients, presenting for major depressive episode (MDE) treatment,
were interviewed using the Structured Clinical Interview for DSM-IV (SCID) and
the Family History Screen. Unipolar patients were divided into highly recurrent
(>4 MDEs) (HRUP) and low recurrent (</=4 MDEs) (LRUP). HRUP had significantly
fewer atypical features and less bipolar II family history than bipolar II, while
age at onset, axis I comorbidity, and depression chronicity were not significantly
different. HRUP had statistically significant lower age at onset, more axis I
comorbidity, more depression chronicity, and clinically significant more atypical
features and more bipolar II family history than LRUP. Results suggest that HRUP
could be midway between bipolar II and LRUP. Pages and Dunner (1997) view that
recurrent unipolar and bipolar II could be part of a single mood disorder, and
Goodwin and Jamison (1990) view that recurrence is the key feature of mood disorders
are partly supported by the findings." [Abstract]
GN, Dikeos DG, Daskalopoulou EG, Soldatos CR.
Co-occurrence of disturbed
sleep and appetite loss differentiates between unipolar and bipolar depressive
Prog Neuropsychopharmacol Biol Psychiatry. 2002
"The aim of this study was to examine whether the co-occurrence
of disturbed sleep and appetite loss, two commonly encountered somatic symptoms
of depression, can differentiate the clinical expression of depressive episodes
between bipolar (BP) and unipolar patients (UP). Forty BP and 40 UP outpatients
were interviewed through the Schedules for the Clinical Assessment in Neuropsychiatry
(SCAN) and the presence of sleep disturbance and appetite loss during their most
severe depressive episode was determined. Other variables studied were patients'
gender and age, clinical characteristics related to the course of the disease
(age at onset, duration of illness, and number and frequency of depressive and
manic episodes), severity of the worst major depressive episode, and presence
or absence of certain associated symptoms during that episode (loss of energy,
low interest, feelings of guilt and/or self-reproach, impaired concentration,
suicidal ideation, and agitation or retardation). Appetite loss was found to be
more frequently present in UP (78%) than BP patients (55%, P<.05). No significant
difference in the occurrence of sleep disturbance was found between the two groups.
Among BP patients, appetite loss was present in 73% of those with sleep disturbance
vs. 33% of those without (P<.02), while no such difference in co-occurrence
of sleep disturbance and appetite loss was noticed among UP patients (74% vs.
85%, respectively, n.s.); this finding did not seem to be related to differences
in severity of depression among UP and BP patients. Furthermore, those BP patients
with co-occurrence of the two somatic symptoms complained also of loss of energy
and low interest more often than those without (P<.01 and P<.05, respectively).
No similar differences were observed among UP patients. The results of the present
study suggest that the pathophysiological mechanisms underlying depressive episodes
may differ between BP and UP affective disorder, and that those BP patients with
simultaneous occurrence of sleep disturbance and appetite loss can be considered
to belong to a particular nosologic subgroup with potential therapeutic and prognostic
L, Mechri A, Gaha L, Khiari G, Zaafrane F, Zougaghi L.
correlated factors in major depression: about 155 Tunisian inpatients]
"The distinction between the depressive troubles
according to their inclusion in bipolar disorders or in recurrent depressive disorders
offers an evident practical interest. In fact, the curative and mainly the preventive
treatment of these troubles are different. So it is necessary to identify the
predictive factors of bipolar development in case of inaugural depressive episode.
In 1983, Akiskal was the first who identified those factors: pharmacological hypomania,
puerperal depression, onset at early age (<25 years), presence of psychotic
characteristics, hypersomnia and psychomotor inhibition. Through this study, the
authors try to compare the epidemiological, clinical and evolution characteristics
of major depression in bipolar disorders to recurrent depressive disorders in
order to indicate the correlated factors with bipolarity. It is a retrospective
and comparative study based on about 155 inpatients for major depressive episode
during the period between January 1994 and December 1998. These patients were
divided into two groups according the DSM IV criteria: bipolar group (96 patients)
and recurrent depressive group (59 patients). Both groups were compared according
to socio-demographic data, life events in childhood, personal and family history,
clinical and evolution characteristics of the index depressive episode. The predictive
factors proposed by Akiskal were systematically examined. It was found out that
the following factors were correlated with bipolarity: high rate of separation
and divorce (17.7% versus 5.1%; p=0.02), family history of psychiatric disorders
(56.3% versus 35.6%; p=0.012) especially bipolar ones (29.2% versus 3.4%; p=0,00008),
onset at early age (mean age of onset: 24.8 8.2 years versus 34.1 12.6 years;
p=0.000004), number of affective episode significantly more frequent (mean 3.6
versus 2.5; p=0.03), sudden onset of depressive episode (44.8% versus 15.9%; p=0.0003)
and presence of psychotic characteristics (69.8% versus 16.7%; p=0.0001) catatonic
characteristics (37.3% versus 20.3%; p=0.03), hypersomnia (51% versus 20.3%; p=0.03)
and psychomotor inhibition (83.3% versus 42.4%; p=0.00007). Negatively correlated
factors of bipolar depression were: somatic comorbidity such as diabetes, hypertension
and rhumatismal diseases (12.5% versus 28.8%; p=0.012) and association with dysthymic
disorders (2.2% versus 12.1%; p=0.029). No correlation was found between bipolarity
and life events in childhood, seasonal character, alcoholic dependence and suicide
attempt. Concerning the validity of predictive factors of bipolarity proposed
by Akiskal, we found: history of bipolar disorders (Sensibility: 29.2%, specificity:
96.6%, Positive Predictive Value (PPV): 93%), hypersomnia (Sensibility: 51%, specificity:
80%, PPV: 80%), onset before the age of 25 years (Sensibility: 62.5%, specificity:
70%, PPV: 77%), psychomotor inhibition (Sensibility: 83.3%, specificity 58%, PPV:
76%), and psychotic characteristics (Sensibility: 69.8%, specificity: 62.7%, PPV:
75%). In spite of methodological differences, our results tallied with the other
studies. We focus on the importance of the bipolar family history criterion, which
has the highest PPV, and the limits of psychotic characteristics criterion which
has the lowest PPV. This may be explained by the frequency of these characteristics
of affective disorders in our cultural context. The association of the hypersomnia
and psychomotor inhibition in one criterion in order to increase their diagnostic
power. Our study helps us to identify the factors that would predict the bipolar
evolution of a depressive episode allowing the use of specific treatment and ensuring
the improvement of prognostic." [Abstract]
AC, Pazzaglia P, Nicholls A, Dougherty DM, Moeller FG.
and phase of illness in bipolar disorder.
J Affect Disord.
"BACKGROUND: Impulsivity is prominent in bipolar
disorder, but there is little quantitative information relating it to phase of
illness. METHODS: We measured impulsivity in patients with bipolar disorder who
had not met episode criteria for at least 6 months, patients who were manic, and
healthy control subjects. Impulsivity was measured using the Barratt Impulsiveness
Scale (BIS) and performance on the computerized Immediate Memory-Remote Memory
Task (IMT-DMT), based on the Continuous Performance Test, which has been shown
to reflect risk of impulsivity in other populations. RESULTS: BIS scores in euthymic
and manic bipolar subjects were identical, and were significantly elevated compared
to controls. Commission errors (impulsive responses) on the IMT-DMT were elevated
in manic subjects but were identical to controls in euthymic subjects. Measures
of impulsivity did not appear related to depressive symptoms. LIMITATIONS: The
number of subjects was too small for detailed investigation of the role of comorbidities;
subjects were receiving pharmacological treatments. CONCLUSIONS: Impulsivity has
state- and trait-related aspects in bipolar disorder." [Abstract]
M, Pirozzi R, Magliano L, Bartoli L.
The prognostic significance
of "switching" in patients with bipolar disorder: a 10-year prospective
Am J Psychiatry. 2002 Oct;159(10):1711-7.
This study explored whether "switching" (i.e., the direct transition
from one mood polarity to the other) has significant prognostic implications in
patients with bipolar disorder. METHOD: Bipolar disorder patients (N=97) whose
first prospectively observed episode included at least one mood polarity switch
and 97 bipolar disorder patients whose index episode was monophasic were compared
with respect to several demographic and historical variables, symptomatic features
of the index episode, time to recovery from the index episode, time spent in an
affective episode during a prospective observation period, and psychopathological
and psychosocial outcome at a 10-year follow-up interview. RESULTS: Patients whose
index episode included at least two mood polarity switches spent significantly
more time in an affective episode during the observation period and had a significantly
worse psychopathological and psychosocial outcome 10 years after recruitment than
those whose index episode included only one mood polarity switch or was monophasic.
Patients whose polyphasic index episode started with depression spent a significantly
higher proportion of time in an affective episode and had a significantly worse
10-year outcome than those whose polyphasic index episode started with mania or
hypomania. Retention of the switching pattern throughout the observation period
was seen in 42.4% of patients whose index episode started with mania and in 65.2%
of those whose index episode started with depression. CONCLUSIONS: An index episode
including at least two mood polarity switches, especially if starting with depression,
is associated with a poor long-term outcome in patients with bipolar disorder.
This pattern represents a significant target for new pharmacological and psychosocial
treatment strategies." [Abstract]
M, Boerlin H, Fairbanks L, Hammen C.
The effect of previous mood
states on switch rates: a naturalistic study.
"OBJECTIVES: A recent study suggested that post-manic
depressions (post-MD) may differ from post-euthymia depression (post-ED). The
goal of this study was to compare the switch rates and length of depressive episodes
stratified by the pre-depression mood states. METHODS: The course of 72 prospectively
observed depressions in 28 patients with Bipolar I depressions were divided into
post-MD versus ED. The two groups, both all episodes and first observed episode,
only were compared in their switch rates and length of episode. RESULTS: Almost
two-thirds (65%) of episodes were rated as ED. There was no difference in switch
rates between the two groups, whether analysed by all episodes, first episodes
only, or episodes not treated with antidepressants. Length of depressive episodes
were also not significantly different between the two groups. DISCUSSION: These
findings do not suggest different switch characteristics between post-MD and post-ED."
F, Golmard JL, Rietschel M, Schulze TG, Malafosse A, Preisig M, McKeon P, Mynett-Johnson
L, Henry C, Leboyer M.
Age at onset in bipolar I affective disorder:
further evidence for three subgroups.
Am J Psychiatry. 2003
"OBJECTIVE: Preliminary data suggested that there
are three subgroups of bipolar affective disorder based on age at onset. The authors
sought to replicate those findings and determine the cut-off age of each subgroup.
METHOD: Admixture analysis was used to determine the best-fitting model for the
observed ages at onset of 368 consecutively admitted patients. The results obtained
were compared with those of the previously described model. The authors also investigated
whether affected siblings are more likely to belong to the same theoretical age-at-onset
subgroup as identified by admixture analysis. RESULTS: The existence of three
subgroups defined by age at onset was confirmed. The mean ages estimated in this
model were 17.4 years (SD=2.3), 25.1 years (SD=6.2), and 40.4 years (SD=11.3).
Affected siblings were more likely to belong to the same theoretical subgroup.
CONCLUSIONS: There are three age-at-onset subgroups of bipolar patients, and specific
familial vulnerability factors might underlie each subgroup." [Abstract]
C, Brandstrom S, Sigvardsson S, Cloninger R, Nylander PO.
disorder. II: personality and age of onset.
"OBJECTIVES: The aim of this study was to examine
whether personality i.e. temperament and character interacts with age of onset
in bipolar disorder. METHODS: Bipolar patients were recruited among in- and outpatients
from lithium dispensaries of northern Sweden. Patients were diagnosed according
to DSM-IV criteria for bipolar disorder type I and II. Temperament and Character
Inventory (TCI) was used for measuring personality. TCI was administered to 100
lithium treated bipolar patients and 100 controls. RESULTS: Treatment response
was significantly lower (p = 0.005) in patients with early onset compared with
late onset. Family history (p = 0.013) and suicide attempts (p = 0.001) were also
significantly more common in patients with early onset. Further, patients with
early onset were significantly higher (p = 0.045) in the temperament factor harm
avoidance (HA) than patients with late onset, but the difference was weak. Patients
with early onset had more fear of uncertainty (HA2; p = 0.022) and were more shy
(HA3; p = 0.030). Bipolar I patients showed similar results as those in the total
bipolar group (I and II), with significantly higher HA (p = 0.019, moderate difference),
HA2 (p = 0.015) and HA3 (p = 0.043) in patients with early onset compared with
late onset. Bipolar II patients showed no differences between early and late age
of onset but the groups are small and the results are therefore uncertain. CONCLUSIONS:
Early age of onset in bipolar disorder was correlated to an increase in severity,
family history, poorer treatment response and poorer prognosis. Early onset was
also correlated to personality." [Abstract]
F, Bellivier F, Jouvent R, Mouren-Simeoni MC, Bouvard M, Allilaire JF, Leboyer
Early and late onset bipolar disorders: two different forms of
J Affect Disord 2000 Jun;58(3):215-21
"BACKGROUND: Conflicting results in genetic studies of bipolar disorders
may be due to the clinical and genetic heterogeneity of the disease. Age at onset
of bipolar disorders may be a key indicator for identifying more homogeneous clinical
subtypes. We tested whether early onset and late onset bipolar illness represent
two different forms of bipolar illness in terms of clinical features, comorbidity
and familial risk. METHODS: Among a consecutively recruited sample of 210 bipolar
patients, we compared early onset (n=58) and late onset (n=39) bipolar patients;
the cut-off points were age at onset before 18 years and after 40 years for the
two subgroups. The subgroups were compared by independent t tests and a contingency
table by raw chi-square test. Morbid risk among first-degree relatives was measured
by the survival analysis method. RESULTS: The early onset group had the most severe
form of bipolar disorder with more psychotic features (P=0.03), more mixed episodes
(P=0.01), greater comorbidity with panic disorder (P=0.01) and poorer prophylactic
lithium response (P=0.04). First degree relatives of early onset patients also
had a higher risk of affective disorders (P=0.0002), and exhibit the more severe
phenotype, i.e bipolar disorder. CONCLUSION: Our data suggest that early and late
onset bipolar disorders differ in clinical expression and familial risk and may
therefore be considered to be different subforms of manic-depressive illness."
Early- versus late-onset bipolar II disorder.
J Psychiatry Neurosci 2000 Jan;25(1):53-7
"OBJECTIVE: To compare the
clinical features and the outcome between patients with early- and late-onset
bipolar II disorder. DESIGN: Case series. SETTING: Outpatient private practice.
PATIENTS: One hundred and seventy-nine consecutive outpatients with bipolar II
disorder presenting for treatment of a major depressive episode. OUTCOME MEASURES:
Duration of illness, severity of depression, recurrences, psychosis, chronicity,
atypical features and comorbidity. RESULTS: Patients with early-onset (before
20, 25 or 30 years of age) bipolar II disorder had a significantly longer duration
of illness and more recurrences compared with patients with late-onset (after
20, 25 or 30 years of age) bipolar II disorder. All other variables were not significantly
different between the 2 groups. CONCLUSIONS: Indicators of worse outcome (severity
of depression, psychosis, chronicity, comorbidity) were not significantly different
between patients with early- and late-onset bipolar II disorder." [Abstract]
SR, Young AH.
Evidence for a late onset bipolar-I disorder sub-group
from 50 years.
J Affect Disord. 2003 Feb;73(3):271-7.
Age of onset has been used to identify aetiological sub-groups in complex inherited
disorders such as Alzheimer's disease and osteoarthritis. We examined the relationship
between age of onset and family history in bipolar-I disorder in an attempt to
identify subgroups. METHODS: All patients discharged from a district in-patient
service diagnosed with bipolar disorder in a 7-year period were ascertained from
a case register (n=277). Diagnosis by DSM-IIIR criteria was confirmed; family
history and age of first admission were recorded from case notes. RESULTS: Age
of first admission in those with a negative family psychiatric history was significantly
older (P=0.029) with a skewed age distribution. This non-familial group contained
significantly more subjects with first admission from the age of 50 years (P=0.007).
CONCLUSIONS: Patients with bipolar-I disorder whose age of first admission is
50 years or above may belong to a different aetiological sub-group." [Abstract]
Aging-related issues in bipolar disorder: a health services perspective.
J Geriatr Psychiatry Neurol. 2002 Fall;15(3):128-33.
"Among the elderly,
bipolar disorder is a significant public health problem, often leading to functional
impairment and substantial use of health care resources. There has been a growing
awareness regarding the manifestations of bipolar disorder among older adults
owing to both changes in national demographics and developing sophistication in
the treatment of bipolar illness. Bipolar disorder accounts for 5% to 19% of mood
disorder presentations in the elderly, although a clear picture of the exact prevalence
of bipolar disorder among older adults in the community is still lacking. Data
from treatment centers give a somewhat unreliable picture of the true prevalence
and manifestations of bipolar disorder in the general population as elderly patients
tend to underuse mental health systems, under-report psychiatric symptoms, and
are often treated in nonhospital/clinic settings, such as nursing homes. Factors
of particular relevance in late-life bipolar disorder include age of onset, symptom
presentation/recognition, secondary mania, psychiatric and medical comorbidity,
and response to treatment. Future mental health services research must further
explore these issues to optimize care for older adults with bipolar disorder."
RM, Calabrese JR, Weissman MM, Reed M, Davies MA, Frye MA, Keck PE Jr, Lewis L,
McElroy SL, McNulty JP, Wagner KD.
Screening for bipolar disorder
in the community.
J Clin Psychiatry. 2003 Jan;64(1):53-9.
Our goal was to estimate the rate of positive screens for bipolar I and bipolar
II disorders in the general population of the United States. METHOD: The Mood
Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and
II disorders, was sent to a sample of 127,800 people selected to represent the
U.S. adult population by demographic variables. 85,358 subjects (66.8% response
rate) that were 18 years of age or above returned the survey and had usable data.
Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S.
Census data completed a telephone interview to estimate nonresponse bias. RESULTS:
The overall positive screen rate for bipolar I and II disorders, weighted to match
the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse
bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens
for bipolar I or II disorders reported that they had previously received a diagnosis
of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis
of unipolar depression. An additional 49.0% reported receiving no diagnosis of
either bipolar disorder or unipolar depression. Positive screens were more frequent
in young adults and low income households. The rates of migraine, allergies, asthma,
and alcohol and drug abuse were substantially higher among those with positive
screens. CONCLUSION: The positive MDQ screen rate of 3.7% suggests that nearly
4% of American adults may suffer from bipolar I and II disorders. Young adults
and individuals with lower income are at greater risk for this largely underdiagnosed
LL, Akiskal HS.
The prevalence and disability of bipolar spectrum
disorders in the US population: re-analysis of the ECA database taking into account
J Affect Disord. 2003 Jan;73(1-2):123-31.
Despite emerging international consensus on the high prevalence of the bipolar
spectrum in both clinical and community samples, many skeptics contend that narrowly
defined bipolar disorder with a lifetime rate of about 1% represents a more accurate
estimate of prevalence. This may in part be due to the fact that higher figures
proposed for the bipolar spectrum (5-8%) have not been based on national data
and have not included all levels of manic symptom severity. In the present secondary
analyses of the US National Epidemiological Catchment Area (ECA) database, we
provide further clarification on this fundamental public health issue. METHODS:
All respondents in the first wave (first interview) of the ECA household five
site sample (n=18252) were classified on the basis of DSM-III criteria into lifetime
manic and hypomanic episodes, as well as those with at least two lifetime manic/hypomanic
symptoms below the threshold for at least 1 week duration (subsyndromal manic
symptoms [SSM] group). Odds ratios were calculated on lifetime service utilization
for mental health problems, measures of adverse psychosocial outcome, and suicidal
behavior compared to subjects with no mental disorders or manic symptoms. RESULTS:
As originally reported nearly two decades ago by the primary investigators of
the ECA, the lifetime prevalence for manic episode was 0.8%, and for hypomania,
0.5%. What is new here is the inclusion of subthreshold SSM subjects, which accounted
for 5.1%, yielding a total of 6.4% lifetime prevalence for the bipolar spectrum.
All three (manic, hypomanic and SSM) groups had greater marital disruption. There
were significant increases in lifetime health service utilization, need for welfare
and disability benefits and suicidal behavior when the SSM, hypomanic and manic
subjects were compared to the no mental disorder group. Suicidal behavior was
non-significantly highest in the hypomanic (bipolar II) group. Otherwise, hypomanic
and manic groups had comparable level of service utilization and social disruption.
LIMITATIONS: Comorbid disorders, which might influence functioning, were not included
in the present analyses. CONCLUSION: These secondary analyses of the US National
ECA database provide convincing evidence for the high prevalence of a spectrum
of bipolarity in the community at 6.4%, and indicate that subthreshold cases are
at least five times more prevalent than DSM-based core syndromal diagnoses at
about 1%. These SSM subjects, who met the criteria of "caseness" from
the point of view of harmful dysfunction, are of great theoretical and public
health significance." [Abstract]
Daniels BA, Kirkby KC, Mitchell P, Hay D, Bowling
Heterogeneity of admission history among patients with bipolar
J Affect Disord. 2003 Jul;75(2):163-70.
Patients on a first admission for bipolar disorder often have a history of other
psychiatric diagnoses for previous admissions. AIMS: The current study examines
the time course and diagnoses of psychiatric admissions prior and subsequent to
a first hospitalisation for a diagnosis of bipolar disorder. METHOD: The prior
admission histories (over the period 1965-1989) of 1167 patients who had been
hospitalised in state mental health facilities with their first admission with
diagnosis of bipolar disorder between 1983 and 1989 were examined. RESULTS: A
total of 542 (46.4%) patients had at least one previous hospitalisation with a
psychiatric diagnosis other than bipolar disorder. Two prominent groups emerged;
one group which had primarily a history of prior admissions with diagnoses of
depression over 1-3 years, and a second which mainly had previous admissions for
schizophrenia, over a period longer than for those with a primarily depressive
history. The group with a history of schizophrenia was significantly younger and
had a greater number of admissions prior to the first bipolar disorder diagnosis
than the depression group. LIMITATIONS: This was a record-based study which did
not examine cases which were not hospitalised. CONCLUSIONS: There appeared to
be three distinct patterns of prior presentations in those patients admitted with
a diagnosis of bipolar disorder." [Abstract]
Morselli PL, Elgie R; GAMIAN-Europe.
survey I--global analysis of a patient questionnaire circulated to 3450 members
of 12 European advocacy groups operating in the field of mood disorders.
Disord. 2003 Aug;5(4):265-78.
"OBJECTIVES: GAMIAN-Europe is a pan-European
federation of national patient organizations from 30 European countries covering
the whole spectrum of psychiatry. To gain a better understanding of what it is
like to live with bipolar disorder (BD), GAMIAN-Europe undertook a detailed patient-based
questionnaire, known as 'GAMIAN-Europe/BEAM Survey', examining a variety of aspects.
METHODS: The questionnaire was mailed to 3450 patients from 12 member organizations
in 11 countries. A total of 1760 completed questionnaires were received but 28
were ruled out as inappropriate. Of the remainder, 1041 respondents stated that
they had been, or were, suffering from BD. The remainder stated that they were
suffering from depression, dysthymia or atypical depression. RESULTS: The findings
indicate that, on average, a bipolar patient is expected to wait for 5.7 years
for a correct diagnosis from the first onset of symptoms. Many patients have a
family history of mood and anxiety disorders. They experience a high degree of
stigmatization from all quarters. This is reflected in the difficulties they experience
in obtaining employment despite high academic achievement. Most patients receive
combination therapy. Compliance problems resulting from adverse side-effects are
less significant than in the past. Overall, the level of satisfaction with pharmacotherapy
was high yet, paradoxically, patients had reservations about dependency issues
and possible long-term side-effects. CONCLUSIONS: There was a clear need for more
patient education about pharmacological and psychosocial interventions, despite
material progress having been made over the past decade. There is an urgent need
for more information and education for both relatives and the public in most European
countries to improve awareness and understanding of BDs and other mood disorders
and the doctor-patient dialogue." [Abstract]
Birnbaum HG, Shi L, Dial E, Oster EF, Greenberg PE,
Economic consequences of not recognizing bipolar disorder
patients: a cross-sectional descriptive analysis.
Psychiatry. 2003 Oct;64(10):1201-9.
"BACKGROUND: This retrospective study
compared treatment patterns and costs for patients with recognized and unrecognized
bipolar disorder with those of depressed patients without a bipolar disorder claim.
METHOD: Claims data for 7 large national employers covering 585,584 persons aged
less than 65 years were used to identify patients diagnosed with depression and
initially treated with antidepressants. Data on employees, as well as spouses
and dependents, for the period 1998 to mid-2001 were used. Patients were identified
as bipolar based on the criteria of a bipolar diagnosis claim (ICD-9 codes: 296.0,
296.1, 296.4-296.8) and/or a mood stabilizer prescription claim. Of the patients
identified as bipolar, unrecognized bipolar disorder (unrecognized-BP) patients
met the criteria after antidepressant initiation, while recognized bipolar disorder
(recognized-BP) patients met the criteria at or before initiation. The remaining
patients in the sample were non-bipolar depressed (non-BP) patients. Outcome measures
included treatment patterns and monthly medical costs in the 12 months subsequent
to initiation of antidepressant treatment. RESULTS: Of the 9009 patients treated
for depression with antidepressants, there were 8383 non-BP patients (93.1%),
293 recognized-BP patients (3.3%), and 333 unrecognized-BP patients (3.7%). Use
of combination therapies varied among the non-BP (11%), unrecognized-BP (32%),
and recognized-BP patients (44%) (all pairwise p <.01). Use of mood stabilizers
was less frequent among unrecognized-BP patients (14%) than recognized-BP patients
(34%) (p <.0001). Unrecognized-BP patients incurred significantly greater (p
<.05) mean monthly medical costs ($1179 US dollars) in the 12 months following
initiation of antidepressant treatment compared with recognized-BP patients ($801
US dollars) and non-BP patients ($585 US dollars). Monthly indirect costs were
significantly greater (p <.05) for unrecognized-BP ($570 US dollars) and recognized-BP
($514 US dollars) employees compared with non-BP employees ($335 US dollars) in
the 12 months following antidepressant initiation. CONCLUSIONS: Patterns of medication
treatment for bipolar disorder were suboptimal. Accurate and timely recognition
of bipolar disease was associated with lower medical costs and lower indirect
costs due to work loss." [Abstract]