Sasson Y, Chopra M, Harrari E, Amitai K, Zohar J.
comorbidity: from diagnostic dilemmas to therapeutic challenge.
J Neuropsychopharmacol. 2003 Jun;6(2):139-44.
"Comorbidity in bipolar
disorder is the rule rather than the exception more than 60% of bipolar patients
have a comorbid diagnosis and is associated with a mixed affective or dysphoric
state; high rates of suicidality; less favourable response to lithium and poorer
overall outcome. There is convincing evidence that rates of substance use and
anxiety disorders are higher among patients with bipolar disorder compared to
their rates in the general population. The interaction between anxiety disorders
and substance use goes both ways: patients with bipolar disorder have a higher
rate of substance use and anxiety disorder, and vice versa. Bipolar disorder is
also associated with borderline personality disorder and ADHD, and to a lesser
extent with weight gain. As more than 40% of bipolar patients have anxiety disorder,
it is indicated that while diagnosing bipolar patients, systematic enquiry about
different anxiety disorders is called for. This also presents a therapeutic challenge,
since agents that effectively treat anxiety disorders are associated with the
risk of induced mania. Therefore, the treating psychiatrist needs to carefully
evaluate the potential benefit of treating the anxiety against the potential cost
of inducing a manic episode. A possible solution would be to use, when possible,
a non-pharmacological intervention, such as a cognitivebehavioural approach. Alternately,
it is suggested that the clinician attempts to ensure that the patient receives
adequate treatment with mood stabilizers before slowly and carefully attempting
the addition of anti-anxiety compounds with a relatively lower risk of mania induction
(e.g. SSRIs compared to TCAs)." [Abstract]
Bipolar disorder: diagnostic
challenges and treatment considerations.
J Clin Psychiatry
2000;61 Supp 13:26-31
"A review of the criteria for the diagnosis of
bipolar disorder identifies a number of complicating factors that historically
have interfered with the accurate and precise diagnosis of patients. Patients
with different subtypes of the disorder sometimes present with different symptoms,
and the careful diagnostician must be aware of them. These include comorbidity
of bipolar disorder and attention-deficit/hyperactivity disorder, comorbidity
of bipolar disorder and substance abuse, and mania secondary to prescription drugs
or physical illness, particularly in the elderly. As a result of these factors
and others. bipolar disorder is significantly underdiagnosed. Accurate and precise
diagnosis has a direct impact on the choice of treatment and will be easier for
those clinicians who are aware of the several subtypes of mania and depression
and are familiar with the relevant Expert Consensus Guidelines for treatment."
DM, Brady KT, Hales RE.
A review of bipolar disorder among adults.
Psychiatr Serv 1999 Feb;50(2):201-13
"OBJECTIVE: This paper reviews the
epidemiology, etiology, assessment, and management of bipolar disorder. Special
attention is paid to factors that complicate treatment, including noncompliance,
comorbid disorders, mixed mania, and rapid cycling. Advances in biopsychosocial
treatments are briefly reviewed, including new health service models for providing
care. METHODS: A MEDLINE search was done for the period from January 1988 through
October 1997 using the key terms of bipolar disorder, diagnosis, and treatment.
Papers selected for further review included those published in English in peer-reviewed
journals. Preference was given to articles reporting randomized, controlled trials.
RESULTS: Bipolar disorder is a major public health problem. The etiology of the
disorder appears multifactorial. Diagnosis often occurs years after onset of the
disorder. Comorbid conditions are common. Management includes a lifetime course
of medication and attention to psychosocial issues for patients and their families.
Standardized treatment guidelines for the management of acute mania have been
developed. New potential treatments are being investigated. CONCLUSIONS: Assessment
of bipolar disorder must include careful attention to comorbid disorders and predictors
of compliance. Randomized trials are needed to further evaluate the efficacy of
medication, psychosocial interventions, and other health service interventions,
particularly as they relate to the management of acute bipolar depression, bipolar
disorder co-occurring with other disorders, and maintenance prophylactic treatment."
C, Van den Bulke D, Bellivier F, Etain B, Rouillon F, Leboyer M.
disorders in 318 bipolar patients: prevalence and impact on illness severity and
response to mood stabilizer.
J Clin Psychiatry. 2003 Mar;64(3):331-5.
The aim of this study was to assess the frequency and impact of anxiety disorders
on illness severity and response to mood stabilizers in bipolar disorders. METHOD:
318 bipolar patients consecutively admitted to the psychiatric wards of 2 centers
as inpatients were recruited. Patients were interviewed with a French version
of the Diagnostic Interview for Genetic Studies providing DSM-IV Axis I diagnoses
and demographic and historical illness characteristics. Logistic and linear regressions
to adjust for age and sex were performed. RESULTS: In a population with mostly
bipolar type I patients (75%), 24% had at least 1 lifetime anxiety disorder (47%
of these patients had more than 1 such disorder), 16% of patients had panic disorder
(with and without agoraphobia, and panic attacks), 11% had phobia (agoraphobia
without panic disorder, social phobia, and other specific phobias), and 3% had
obsessive-compulsive disorder. Comorbidity with anxiety disorders was not correlated
with severity of bipolar illness as assessed by the number of hospitalizations,
psychotic characteristics, misuse of alcohol and drugs, and suicide attempts (violent
and nonviolent). Bipolar patients with an early onset of illness had more comorbidity
with panic disorder (p <.05). Anxiety disorders were detected more frequently
in bipolar II patients than in other patients, but this difference was not significant
(p =.09). Bipolar patients with anxiety responded less well to anticonvulsant
drugs than did bipolar subjects without anxiety disorder (p <.05), whereas
the efficacy of lithium was similar in the 2 groups. There was also a strong correlation
between comorbid anxiety disorders and depressive temperament in bipolar patients
(p =.004). CONCLUSION: Patients with bipolar disorders often have comorbid anxiety
disorders, particularly patients with depressive temperament, and the level of
comorbidity seems to decrease the response to anticonvulsant drugs." [Abstract]
SC, Chen YW.
Social phobia, panic disorder and suicidality in subjects
with pure and depressive mania.
J Affect Disord. 2003 Nov;77(2):173-7.
The objective of this study is to ascertain the rates of social phobia, panic
disorder and suicidality in the midst of the manic state among subjects with pure
and depressive mania. METHODS: Subjects received evaluations entailing the use
of serial standard clinical interviews, the Schedule for Affective Disorders and
Schizophrenia (SADS) and a structured interview to determine whether they met
the criteria for intra-episode social phobia (IESP) and panic disorder (IEPD).
The diagnoses of major depressive disorder and mania were rendered using the Research
Diagnostic Criteria. The diagnoses of IESP and IEPD were rendered using DSM-III-R
criteria. Categorization as being suicidal was based on the SADS suicide subscale
score. RESULTS: Twenty-five (56.8%) subjects had pure and 19 (43.2%) subjects
had depressive mania. None of the subjects with pure and 13 (68.4%) with depressive
mania had IESP (P<0.0001). One (4.0%) subject with pure and 16 (84.2%) subjects
with depressive mania had IEPD (P<0.0001). One (4.0%) subject with pure and
12 (63.2%) subjects with depressive were suicidal. Twelve of 13 (92.3%) subjects
with depressive mania met the criteria for IESP and IEPD concurrently (P<0.0001).
All were suicidal. LIMITATIONS: The study suffers limitations imposed by small
sample sizes and non-blind methods of identifying subjects with IESP, IEPD and
who were suicidal. CONCLUSIONS: Subjects with depressive but not pure mania exhibited
high rates of both IESP and IEPD. Concurrence of the disorders is the rule. The
findings suggest that databases disclosing a relationship between panic disorder
and suicidality merit, where possible, reanalysis directed at controlling for
the effect of social phobia." [Abstract]
Tamam L, Ozpoyraz N.
anxiety disorder among patients with bipolar I disorder in remission.
"The aim of this study was to assess the comorbidity
of lifetime and current prevalences of anxiety disorders among 70 patients with
bipolar I disorder in remission using structured diagnostic interviews and to
examine the association between comorbidity and several demographic and clinical
variables. Forty-three (61.4%) bipolar I patients also met DSM-IV criteria for
at least one lifetime comorbid anxiety disorder. Obsessive-compulsive disorder
(39%) was the most common comorbid lifetime anxiety disorder, followed by simple
phobia (26%) and social phobia (20%). First episode and male sex were found to
have lower rates of comorbid current anxiety disorders. The presence of anxiety
disorders was related to significantly higher scores on both anxiety and general
psychopathology scales. The results of the present study support previous findings
of a high comorbidity rate of anxiety disorders in bipolar I disorder cases and
indicate that the presence of an anxiety disorder leads to more severe psychopathology
levels in bipolar I patients." [Abstract]
J, Biederman J, Monuteaux MC, Richards J, Faraone SV.
comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis.
J Child Adolesc Psychopharmacol 2002 Summer;12(2):101-11
A growing literature suggests that anxiety disorders (ANX) co-occur with bipolar
disorder (BPD), but the nature of this overlap is unknown. Thus, we investigated
the familial association between BPD and ANX among the first-degree relatives
of children with BPD with and without comorbid ANX. METHODS: We compared relatives
of four proband groups defined by the presence or absence of BPD and ANX in the
proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2) BPD without ANX (n
= 11 probands, 38 relatives), (3) ANX without BPD (n = 48 probands, 167 relatives),
and (4) controls without BPD or ANX (n = 118 probands, 385 relatives). All subjects
were evaluated with structured diagnostic interviews. Diagnoses of relatives were
made blind to the diagnoses of probands. RESULTS: The results show high rates
of both BPD and ANX in relatives of children with BPD + ANX. Moreover, BPD and
ANX cosegregated among the relatives of children with BPD + ANX. Although relatives
of both ANX proband groups (with and without BPD) had high rates of ANX, and relatives
of both BPD proband groups (with and without ANX) had high rates of BPD, the combined
condition BPD + ANX was the predominant form of BPD among relatives of probands
with BPD + ANX. CONCLUSIONS: These family-genetic findings suggest that the comorbid
condition BPD+ANX may be a distinct clinical entity. More work is needed to evaluate
whether the presence of comorbid ANX may be a marker of very early onset BPD."
NM, Smoller JW, Fava M, Sachs G, Racette SR, Perlis R, Sonawalla S, Rosenbaum
Comparing anxiety disorders and anxiety-related traits in bipolar
disorder and unipolar depression.
J Psychiatr Res. 2003
"The frequent comorbidity of anxiety disorders and
mood disorders has been documented in previous studies. However, it remains unclear
whether specific anxiety traits or disorders are more closely associated with
unipolar major depression (MDD) or bipolar disorder (BPD). We sought to examine
whether MDD and BPD can be distinguished by their association with specific types
of anxiety comorbidity. Individuals with a primary lifetime diagnosis of either
bipolar disorder (N=122) or major depressive disorder (N=114) received diagnostic
assessments of anxiety disorder comorbidity, and completed questionnaires assessing
anxiety sensitivity and neuroticism. The differential association of these anxiety
phenotypes with MDD versus BPD was examined with multivariate modeling. Panic
disorder and generalized anxiety disorder (GAD) specifically emerged amongst all
the anxiety disorders as significantly more common in patients with BPD than MDD.
After controlling for current mood state, anxiety sensitivity and neuroticism
did not differ by mood disorder type. This study supports prior research suggesting
a specific panic disorder-bipolar disorder connection, and suggests GAD may also
be differentially associated with BPD. Further research is needed to clarify the
etiologic basis of anxiety disorder/BPD comorbidity and to optimize treatment
strategies for patients with these co-occurring disorders." [Abstract]
SH, Hewitt JK, Corley RP, Stallings MC.
The validity of analyses
testing the etiology of comorbidity between two disorders: a review of family
J Child Psychol Psychiatry. 2003 May;44(4):612-36.
Knowledge regarding the causes of comorbidity between two disorders has a significant
impact on research regarding the classification, treatment, and etiology of the
disorders. Two main analytic methods have been used to test alternative explanations
for the causes of comorbidity in family studies: biometric model fitting and family
prevalence analyses. Unfortunately, the conclusions of family studies using these
two methods have been conflicting. In the present study, we examined the validity
of family prevalence analyses in testing alternative comorbidity models. METHOD:
We reviewed 42 family studies that used family prevalence analyses to test three
comorbidity models: the alternate forms model, the correlated liabilities model,
or the three independent disorders model. We conducted the analyses used in these
studies on datasets simulated under the assumptions of 13 alternative comorbidity
models including the three models tested most often in the literature. RESULTS:
Results suggest that some analyses may be valid tests of the alternate forms model
(i.e., two disorders are alternate manifestations of a single liability), but
that none of the analyses are valid tests of the correlated liabilities model
(i.e., a significant correlation between the risk factors for the two disorders)
or the three independent disorders model (i.e., the comorbid disorder is a third,
independent disorder). CONCLUSION: Family studies using family prevalence analyses
may have made incorrect conclusions regarding the etiology of comorbidity between
RD, Hoven CW.
Bipolar-panic comorbidity in the general population:
prevalence and associated morbidity.
J Affect Disord 2002
E, Cyranowski JM, Rucci P, Shear MK, Fagiolini A, Thase ME, Cassano GB, Grochocinski
VJ, Kostelnik B, Kupfer DJ.
Clinical significance of lifetime panic
spectrum symptoms in the treatment of patients with bipolar I disorder.
Gen Psychiatry. 2002 Oct;59(10):905-11.
"BACKGROUND: Given the observed
association between panic disorder and bipolar disorder and the potential negative
influence of panic symptoms on the course of bipolar illness, we were interested
in the effects of what we have defined as "panic spectrum" conditions
on the clinical course and treatment outcome in patients with bipolar I (BPI)
disorder. We hypothesized that lifetime panic spectrum features would be associated
with higher levels of suicidal ideation and a poorer response to acute treatment
of the index mood episode in this patient population. METHODS: A sample of 66
patients with BPI disorder completed a self-report measure of lifetime panic-agoraphobic
spectrum symptoms. Patients falling above and below a predefined clinical threshold
for panic spectrum were compared for clinical characteristics, the presence of
suicidal ideation during acute treatment, and acute treatment response. RESULTS:
Half of this outpatient sample reported panic spectrum features above the predefined
threshold. These lifetime features were associated with more prior depressive
episodes, higher levels of depressive symptoms, and greater suicidal ideation
during the acute-treatment phase. Patients with BPI disorder who reported high
lifetime panic-agoraphobic spectrum symptom scores took 27 weeks longer than those
who reported low scores to remit with acute treatment (44 vs 17 weeks, respectively).
CONCLUSIONS: The presence of lifetime panic spectrum symptoms in this sample of
patients with BPI disorder was associated with greater levels of depression, more
suicidal ideation, and a marked (6-month) delay in time to remission with acute
treatment. Alternate treatment strategies are needed for patients with BPI disorder
who endorse lifetime panic spectrum features." [Abstract]
DF, McMahon FJ, Simpson SG, McInnis MG, DePaulo JR.
with familial bipolar disorder.
Biol Psychiatry 1997 Jul
"If bipolar disorder is genetically heterogeneous, it may
be possible to discern clinically heterogeneous familial subtypes based on differential
risk for psychiatric comorbidity, for example panic disorder. We evaluated 528
members of 57 families ascertained for a genetic linkage study of bipolar disorder.
Families were assorted according to the panic disorder diagnosis of the bipolar
proband; the rates of panic and other disorders in relatives were compared. Eighty-eight
percent of the 41 subjects with panic disorder had bipolar disorder. Panic disorder
was diagnosed in 18% of family members with bipolar disorder. Ten of 57 bipolar
probands had panic disorder. Their bipolar first-degree relatives had a significantly
higher prevalence of panic disorder, bipolar II, cyclothymia, and dysthymia, but
had lower prevalence of substance abuse than the relatives of the bipolar probands
without panic disorder. These findings suggest the testable hypothesis that comorbid
panic disorder is a marker of genetic heterogeneity in bipolar disorder."
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
N, Terman M, Terman JS.
Depressive symptomatology differentiates
subgroups of patients with seasonal affective disorder.
Depress Anxiety 2002;15(1):34-41
"Patients with seasonal affective disorder
(SAD) may vary in symptoms of their depressed winter mood state, as we showed
previously for nondepressed (manic, hypomanic, hyperthymic, euthymic) springtime
states [Goel et al., 1999]. Identification of such differences during depression
may be useful in predicting differences in treatment efficacy or analyzing the
pathogenesis of the disorder. In a cross-sectional analysis, we determined whether
165 patients with Bipolar Disorder (I, II) or Major Depressive Disorder (MDD),
both with seasonal pattern, showed different symptom profiles while depressed.
Assessment was by the Structured Interview Guide for the Hamilton Depression Rating
Scale-Seasonal Affective Disorder Version (SIGH-SAD), which includes a set of
items for atypical symptoms. We identified subgroup differences in SAD based on
categories specified for nonseasonal depression, using multivariate analysis of
variance and discriminant analysis. Patients with Bipolar Disorder (I and II)
were more depressed (had higher SIGH-SAD scores) and showed more psychomotor agitation
and social withdrawal than those with MDD. Bipolar I patients had more psychomotor
retardation, late insomnia, and social withdrawal than bipolar II patients. Men
showed more obsessions/compulsions and suicidality than women, while women showed
more weight gain and early insomnia. Whites showed more guilt and fatigability
than blacks, while blacks showed more hypochondriasis and social withdrawal. Darker-eyed
patients were significantly more depressed and fatigued than blue-eyed patients.
Single and divorced or separated patients showed more hypochondriasis and diurnal
variation than married patients. Employed patients showed more atypical symptoms
than unemployed patients, although most of the subgroup distinctions lay on the
Hamilton Scale. These results comprise a set of biological and sociocultural factors-including
race, gender, and marital and employment status-which contribute to depressive
symptomatology in SAD. Significant mood and sociocultural factors, in contrast
to biological factors of gender and eye color, were similar to those reported
for nonseasonal depression. Lightly pigmented eyes, in particular, may serve to
enhance photic input during winter and allay depressive symptoms in vulnerable
EG, Angst J, Demonfaucon C, Perugi G, Lancrenon S, Akiskal HS.
OCD: a distinct form?
J Affect Disord. 2003 Jun;75(1):1-10.
Clinical research on the comorbidity of obsessive compulsive disorder (OCD) and
other anxiety disorders has largely focused on depression. However in practice,
resistant or severe OCD patients not infrequently suffer from a masked or hidden
comorbid bipolar disorder. METHOD: The rate of bipolar comorbidity in OCD was
systematically explored among 453 members of the French Association of patients
suffering from OCD (AFTOC) as well as a psychiatric sample of OCD out-patients
(n=175). As previous research by us has shown the epidemiologic and clinical sample
to be similar, we combined them in the present analyses (n=628). To assess mood
disorder comorbidity, we used structured self-rated questionnaires for major depression,
hypomania and mania (DSM-IV criteria), self-rated Angst's checklist of Hypomania
and that for the Cyclothymic Temperament (French version developed by Akiskal
and Hantouche). RESULTS: According to DSM-IV definitions of hypomania/mania, 11%
of the total combined sample was classified as bipolar (3% BP-I and 8% BP-II).
When dimensionally rated, 30% obtained a cut-off score >/=10 on the Hypomania
checklist and 50% were classified as cyclothymic. Comparative analyses were conducted
between OCD with (n=302) versus without cyclothymia (n=272). In contrast to non-cyclothymics,
the cyclothymic OCD patients were characterized by more severe OCD syndromes (higher
frequencies of aggressive, impulsive, religious and sexual obsessions, compulsions
of control, hoarding, repetition); more episodic course; greater rates of manic/hypomanic
and major depressive episodes (with higher intensity and recurrence) associated
with higher rates of suicide attempts and psychiatric admissions; and finally,
a less favorable response to anti-OCD antidepressants and elevated rate of mood
switching with aggressive behavior. LIMITATION: Hypomania and cyclothymia were
not confirmed by diagnostic interview by a clinician. CONCLUSION: Our data extend
previous research on "OCD-bipolar comorbidity" as a highly prevalent
and largely under-recognized and untreated class of OCD patients. Furthermore,
our data suggest that "cyclothymic OCD" could represent a distinct form
of OCD. More attention should be paid to it in research and clinical practice."
EG, Demonfaucon C, Angst J, Perugi G, Allilaire JF, Akiskal HS.
obsessive-compulsive disorder. Clinical characteristics of a neglected and under-recognized
Presse Med 2002 Apr 13;31(14):644-8
Clinical research is largely focused on depressive comorbidity in obsessional
compulsive disorder (OCD). However some recent publications have suggested that
bipolar comorbidity occurs in authentic OCD and its presence has a differential
impact on the clinical picture and course of OCD. METHOD: Recent data from the
collaborative survey conducted with AFTOC (French Association of patients suffering
from OCD) have revealed a high rate of bipolar comorbidity in OCD: 30% for hypomania
and 50% for cyclothymia. RESULTS: The present paper presents further comparative
analyses between OCD with (n = 302) versus without cyclothymia (n = 272). The
sub-group "Cyclothymic OCD" is characterized by a different clinical
picture (higher frequency of aggressive, impulsive, religious and sexual obsessions,
and compulsions of control, hoarding, repetition), episodic course, higher rate
of major depressive episodes (with more intensity and recurrence) associated with
higher rates of suicide attempts and psychiatric admissions, and less favorable
response to anti-OCD treatments. CONCLUSION: These data suggested that cyclothymic
OCD could represent a specific distinct variant form of OCD. More vigilance is
needed toward this entity which is largely under-recognized in clinical practice."
EG, Kochman F, Demonfaucon C, Barrot I, Millet B, Lancrenon S, Akiskal HS.
obsessive-compulsive disorder: confirmation of results of the "ABC-OCD"
survey in 2 populations of patient members versus non-members of an association]
"Clinical data are largely focused on depressive
comorbidity in OCD. However in practice, treating resistant or severe OCD sufferers
revealed many cases who seem to have an authentic OCD with a hidden comorbid bipolar
disorder. Most reports had evaluated the OCD comorbidity in unipolar and bipolar
mood disorders (Kruger et al., 1995; Chen et Dilsaver, 1995). The only investigation
in clinical population focused on the reverse issue was conducted in Pisa. Perugi
et al. (1997) have showed in a consecutive series of 315 OCD outpatients, that
15.7% presented a bipolar comorbidity, mostly with BP-II disorder. Further analyses
suggested that when comorbidity occurs with bipolar and unipolar depression, it
has a differential impact on the clinical picture and course of OCD. The rate
of bipolar comorbidity in OCD was analyzed in a recent epidemiological survey
undertaken by the French Association of patients suffering from OCD (FA-OCD or
AFTOC in French). In a sample of 453 OCD patients, 76% had suffered from a major
depression, 11% from bipolar disorder (DSM IV mania or hypomania), 30% from hypomania
(cases that obtained a score > or = 10 on the self-rated Angst Hypomania Checklist).
According to the score > or = 10 on Self-rated Questionnaire for Cyclothymic
Temperament, 50% were classified as cyclothymic. The self-assessment of soft-bipolar
dimensions, such as hypomania and cyclothymia was previously validated in a multi-site
study in major depression (Hantouche et al., 1998). Further analyses showed that
comorbidity with soft bipolarity was characterized by significant interactions
with high levels of impulsivity, anger attacks and suicidal behavior. In order
to confirm these data, another cohort (n = 175 patients treated by psychiatrists
for OCD) was formed and named "PSY-OCD". Comparative analyses between
the two populations allowed showing very few demographic and clinical differences.
The frequency rate of "bipolar OCD" was equivalent in both populations:
BP-II disorder (DSM IV criteria) was present in 11% of FA-OCD and 16% of PSY-OCD.
Furthermore using the Hypomania Checklist showed that BP-II disorder rate (score
> or = 10) was higher: 32% of in both populations. Cyclothymic rate was also
globally higher, but significant difference was obtained: 56% of FA-OCD versus
45% of PSY-OCD (p = 0.02). Moreover, mood switching rate under anti-OCD drugs
was equivalent in both OCD populations (respectively 38% and 33%, p = ns). In
case of BP comorbidity, patients had presented a greater number of concurrent
major depressive episodes and suicidal attempts. When concurrent depression was
considered, the rate diagnosis of soft bipolarity was 2.5 fold, and the number
of suicidal attempts augmented by 7 fold (by comparison versus non-depressed OCD).
Despite very early descriptions (since the beginning of the last century) of particular
relationships between so-called "psychasthenia, folie de doute, folie raisonnante"
and "circular and intermittent madness or cyclothymia", a few attention
has been devoted to this complex pattern of comorbidity. The comparative data
deriving from the collaborative survey with patients who are members of AFTOC
and with a cohort of psychiatric outpatients, confirm the reality of bipolar-OCD
comorbidity, which is largely under-recognized in clinical practice. More in depth
analyses are now undertaken in order to investigate the characteristics of "bipolar
OCD" by comparison to "non bipolar OCD"." [Abstract]
S, Braunig P, Cooke RG.
Comorbidity of obsessive-compulsive disorder
in recovered inpatients with bipolar disorder.
Disord 2000 Mar;2(1):71-4
"OBJECTIVE: To determine the frequency of obsessive-compulsive
disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine
the clinical characteristics of BD subjects with OCD. METHOD: The sample consisted
of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from
a current episode of either depression or mania. Demographic and clinical variables
were obtained on the day of admission. Current comorbid conditions including OCD
were determined by the Structured Clinical Interview for DSM-III-R Ifollowing
recovery from the acute affective episode. RESULTS: The frequency of current OCD
was 7% (N = 10). All BD subjects with OCD were BD-II, were male, and had a diagnosis
of current dysthymia. They had fewer episodes and a higher incidence of prior
suicide attempts than bipolar subjects without OCD. None of the bipolar subjects
with OCD fulfilled criteria for cyclothymia. CONCLUSIONS: Our findings suggest
that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects
with BD. We discuss the clinical implications of our findings." [Abstract]
Borderline personality disorder and bipolar II disorder in private
practice depressed outpatients.
Compr Psychiatry 2000 Mar-Apr;41(2):106-10
"Bipolar II disorder (BDII) may be confused with borderline personality disorder
(BPD) when it is cyclothymic between episodes. The aim of the present study was
to determine the prevalence of BPD and to test whether BDII can be distinguished
from BPD without difficulty in private practice mood disorder outpatients. Private
practice was chosen because it is often the first or second line of treatment
of mood disorders in Italy, and many "soft" patients can be found in
this setting. Among 63 consecutive unipolar and 50 bipolar II major depressive
episode (MDE) outpatients interviewed with the Structured Clinical Interviews
for DSM-IV axis I/II disorders (SCIDs), the prevalence of BPD was 6.1% and was
significantly higher in BDII patients (12% v. 1.5%). Overall, the rate of BPD
diagnosis was very low. BDII was distinguished from BPD without difficulty by
DSM-IV criteria. The results suggest that there may be a subgroup of BDII patients
with a relatively stable course between episodes (or at least not so unstable
as to suggest a BPD diagnosis or comorbidity) and a low comorbidity with BPD,
in a setting closer to community patients than university settings. The "usual"
BDII patient can be distinguished from the BPD patient." [Abstract]
J, Faraone SV, Wozniak J, Monuteaux MC.
Parsing the association
between bipolar, conduct, and substance use disorders: a familial risk analysis.
Biol Psychiatry 2000 Dec 1;48(11):1037-44
"BACKGROUND: Bipolar disorder
has emerged as a risk factor for substance use disorders (alcohol or drug abuse
or dependence) in youth; however, the association between bipolar disorder and
substance use disorders is complicated by comorbidity with conduct disorder. We
used familial risk analysis to disentangle the association between the three disorders.
METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar
disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without
bipolar disorder, and 4) control subjects without bipolar disorder or conduct
disorder. All subjects were evaluated with structured diagnostic interviews. For
the analysis of substance use disorders, Cox proportional hazard survival models
were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder
in probands was a risk factor for both drug and alcohol addiction in relatives,
independent of conduct disorder in probands, which was a risk factor for alcohol
dependence in relatives independent of bipolar disorder in probands, but not for
drug dependence. The effects of bipolar disorder and conduct disorder in probands
combined additively to predict the risk for substance use disorders in relatives.
CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts
especially high rates of substance use disorders in relatives. These findings
support previous results documenting that when bipolar disorder and conduct disorder
occur comorbidly, both are validly diagnosed disorders." [Abstract]
NN, Davidson PW, Burhan AM, Andolsek ME, Baxter JT, Sullivan L, Florescue H, List
A, Deutsch L.
Identifying bipolar disorders in individuals with intellectual
J Intellect Disabil Res. 2003 Jan;47(Pt 1):31-8.
The aim of the present study was to characterize adults with intellectual disability
(ID) and concomitant clinical diagnoses of bipolar disorder (BPD), and determine
whether DSM-IV criteria would distinguish individuals with BPD from patients with
other psychiatric diagnoses. METHODS: A retrospective chart review was done of
a convenience sample of adult patients seen over a 3-year period in a specialty
clinic for adults with ID and psychiatric disorders. The DSM-IV criteria were
used to differentiate individuals with clinical symptoms of BPD from groups of
patients with other mood or thought disorders with behavioural symptoms which
frequently overlap those of BPD. Behavioural symptoms were also catalogued and
used to distinguish the diagnostic groups. RESULTS: Subjects with clinical symptoms
of BPD had significantly more DSM-IV mood-related and non-mood-related symptoms,
as well as functional impairments, compared to individuals with major depression,
depression with psychosis or schizophrenia/psychosis NOS (not otherwise specified).
Likewise, behavioural profiles of the BPD group of patients differed significantly
from patients in the other three groups. CONCLUSIONS: Bipolar disorder can be
readily recognized and distinguished from other behavioural and psychiatric diagnoses
in individuals with ID, and DSM-IV criteria can be useful in the diagnosis of
Cannas A, Spissu A, Floris GL, Congia S, Saddi MV,
Melis M, Mascia MM, Pinna F, Tuveri A, Solla P, Milia A, Giagheddu M, Tacconi
Bipolar affective disorder and Parkinson's disease: a rare, insidious
and often unrecognized association.
Neurol Sci. 2002 Sep;23
"Five patients (4 women) with Parkinson's disease (PD)
and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the
diagnosis of bipolar affective disorder (BAD) were studied. Four patients had
early onset PD. Four developed a severe psychiatric disorder a few years after
starting dopaminergic therapy in presence of a mild motor disability and a mild
cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients
developed a clear manic episode; the other three presented a severe depressive
episode (in one case featuring a Cotard syndrome). None showed previous signs
of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric
disorders. The two manic episodes occurred shortly after an increase of dopaminergic
therapy and in one case rapid cyclic mood fluctuations were observed. At the onset
of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional
hallucinatory psychosis (CDHP)." [Abstract]
F, Vieta E, Martinez-Aran A, Reinares M, Benabarre A, Gasto C.
factors associated with treatment noncompliance in euthymic bipolar patients.
J Clin Psychiatry 2000 Aug;61(8):549-55
"BACKGROUND: Noncompliance with
medication is a very common feature among bipolar patients. Rates of poor compliance
may reach 64% for bipolar disorders, and noncompliance is the most frequent cause
of recurrence. Knowledge of the clinical factors associated with noncompliance
would enhance clinical management and the design of strategies to achieve a better
outcome for bipolar patients. Although most patients withdraw from medication
during maintenance treatment, compliance studies in euthymic bipolar samples are
scarce. METHOD: Compliance treatment and its clinical correlates were assessed
at the end of 2-year follow-up in 200 patients meeting Research Diagnostic Criteria
for bipolar I or bipolar II disorder by means of compliance-focused interviews,
measurements of plasma concentrations of mood stabilizers, and 2 structured interviews:
the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical
Interview for DSM-III-R Axis II disorders. Well-compliant patients and poorly
compliant patients were compared with respect to several clinical and treatment
variables. RESULTS: The rate of mildly and poorly compliant patients was close
to 40%. Comorbidity with personality disorders was strongly associated with poor
compliance. Poorly compliant patients had a higher number of previous hospitalizations,
but reported fewer previous episodes. The type of treatment was not associated
with compliance. CONCLUSION: Clinical factors, especially comorbidity with personality
disorders, are more relevant for treatment compliance than other issues such as
the nature of pharmacologic treatment. Compliant patients may have a better outcome
in terms of number of hospitalizations, but not necessarily with respect to the
number of episodes. Bipolar patients, especially those with personality disorders,
should be monitored for treatment compliance." [Abstract]
McElroy SL, Altshuler LL, Suppes T, Keck PE Jr,
Frye MA, Denicoff KD, Nolen WA, Kupka RW, Leverich GS, Rochussen JR, Rush AJ,
Axis I psychiatric comorbidity and its relationship to
historical illness variables in 288 patients with bipolar disorder.
Am J Psychiatry 2001 Mar;158(3):420-6
"OBJECTIVE: Bipolar disorder often
co-occurs with other axis I disorders, but little is known about the relationships
between the clinical features of bipolar illness and these comorbid conditions.
Therefore, the authors assessed comorbid lifetime and current axis I disorders
in 288 patients with bipolar disorder and the relationships of these comorbid
disorders to selected demographic and historical illness variables. METHOD: They
evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic
interviews and clinician-administered and self-rated questionnaires to determine
the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic
and historical illness characteristics. RESULTS: One hundred eighty-seven (65%)
of the patients with bipolar disorder also met DSM-IV criteria for at least one
comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders
(N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders
(N=9, 5%). There were no differences in comorbidity between patients with bipolar
I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I
comorbidity were associated with earlier age at onset of affective symptoms and
syndromal bipolar disorder. Current axis I comorbidity was associated with a history
of development of both cycle acceleration and more severe episodes over time.
CONCLUSIONS: Patients with bipolar disorder often have comorbid anxiety, substance
use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity,
especially current comorbidity, may be associated with an earlier age at onset
and worsening course of bipolar illness. Further research into the prognostic
and treatment response implications of axis I comorbidity in bipolar disorder
is important and is in progress." [Abstract]
JH, Altshuler LL, Ventura J, Mintz J.
Impact of axis II comorbidity
on the course of bipolar illness in men: a retrospective chart review.
Disord. 2002 Aug;4(4):237-42.
"OBJECTIVES: The purpose of this study was
to investigate whether the presence of comorbid personality disorder influences
the course of bipolar illness. METHODS: Fifty-two euthymic male bipolar I out-patients
were assessed using the Structured Clinical Interview for DSM-III-R Personality
Disorders (SCID II). Bipolar patients with an axis II diagnosis were compared
with those without an axis II diagnosis on retrospectively obtained demographic,
clinical and course of illness variables. RESULTS: Thirty-eight percent of the
bipolar patients met criteria for an axis II diagnosis. Two (4%) met criteria
for (only) a Cluster A disorder, four (8%) for (only) a Cluster B, and six (12%)
for (only) a Cluster C disorder. One (2%) bipolar patient met criteria a disorder
in both Clusters A and B, and one (2%) for a disorder in Clusters B and C. Five
(10%) met criteria for at least one disorder in Clusters A and C, and one met
criteria for disorders in Clusters A, B, and C. The presence of a personality
disorder was significantly associated with a lower rate of current employment,
a higher number of currently prescribed psychiatric medications, and a higher
incidence of a history of both alcohol and substance use disorders compared with
the bipolar patients without axis II pathology. CONCLUSIONS: Our results extend
previous findings of an association between comorbid personality disorder in bipolar
I patients and factors that suggest a more difficult course of bipolar illness."
EL, Miklowitz DJ, Richards JA, Simoneau TL, Taylor DO.
of bipolar disorder and axis II personality disorders: prevalence and clinical
Bipolar Disord. 2003 Apr;5(2):115-22.
Many studies have examined the prevalence and predictive validity of axis II personality
disorders among unipolar depressed patients, but few have examined these issues
among bipolar patients. The few studies that do exist suggest that axis II pathology
complicates the diagnosis and course of bipolar disorder. This study examined
the prevalence of axis II disorder in bipolar patients who were clinically remitted.
METHODS: We assessed the co-occurrence of personality disorder among 52 remitted
DSM-III-R bipolar patients using a structured diagnostic interview, the Personality
Disorder Examination (PDE). RESULTS: Axis II disorders can be rated reliably among
bipolar patients who are in remission. Co-diagnosis of personality disorder occurred
in 28.8% of patients. Cluster B (dramatic, emotionally erratic) and cluster C
(fearful, avoidant) personality disorders were more common than cluster A (odd,
eccentric) disorders. Bipolar patients with personality disorders differed from
bipolar patients without personality disorders in the severity of their residual
mood symptoms, even during remission. CONCLUSIONS: When structured assessment
of personality disorder is performed during a clinical remission, less than one
in three bipolar patients meets full syndromal criteria for an axis II disorder.
Examining rates of comorbid personality disorder in broad-based community samples
of bipolar spectrum patients would further clarify the linkage between these sets
of disorders." [Abstract]
PJ, MacQueen GM, Marriot MJ, Robb JC, Begin H, Joffe RT, Young LT.
outcome in patients with bipolar disorder assessed by life-charting is influenced
by DSM-IV personality disorder symptoms.
"OBJECTIVES: Few studies have examined the question
of how personality features impact outcome in bipolar disorder (BD), though results
from extant work and studies in major depressive disorder suggest that personality
features are important in predicting outcome. The primary purpose of this paper
was to examine the impact of DSM-IV personality disorder symptoms on long-term
clinical outcome in BD. METHODS: The study used a 'life-charting' approach in
which 87 BD patients were followed regularly and treated according to published
guidelines. Outcome was determined by examining symptoms over the most recent
year of follow-up and personality symptoms were assessed with the Structured Clinical
Interview for DSM-IV (SCID-II) instrument at entry into the life-charting study.
RESULTS: Patients with better outcomes had fewer personality disorder symptoms
in seven out of 10 disorder categories and Cluster A personality disorder symptoms
best distinguished euthymic and symptomatic patients. CONCLUSIONS: These results
raise important questions about the mechanisms linking personality pathology and
outcome in BD, and argue that conceptual models concerning personality pathology
and BD need to be further developed. Treatment implications of our results, such
as need for psychosocial interventions and treatment algorithms, are also described."
P, Ehrt U, Marneros A.
Frequency of comorbid personality disorders
in bipolar and unipolar affective disorders.
"One expression of the complex relationship
between personality and affective disorder is the comorbidity of personality disorders
(PDs) with affective disorders. In a sample of 117 patients with unipolar and
60 with bipolar affective disorders, we assessed DSM-III-R PDs with the Structured
Clinical Interview for DSM-IV Personality Disorders (SCID-II) and compared them
with personality factors as obtained by the five-factor model (FFM-NEO Five-Factor
Inventory). Fifty-one percent of the unipolar and 38% of the bipolar disorders
fulfilled criteria for a comorbid PD. The three most frequent PDs were obsessive-compulsive
PD, borderline PD, and narcissistic (bipolar) or avoidant (unipolar) PD. Cluster
C PDs and especially avoidant PD occurred significantly more frequently in unipolar
than in bipolar patients, while narcissistic PD occurred significantly more often
in bipolar than in unipolar patients. The FFM results supported the validity of
our PD diagnoses. In a logistic regression analysis, higher depression score at
the time of the SCID-II interview and shorter duration of the illness were weakly
related to a higher frequency of PDs. Our results indicate that PDs are frequent
in affective disorders and that there are subtle differences between unipolar
and bipolar patients concerning such comorbid disorders." [Abstract]
Vieta E, Colom F, Martinez-Aran A, Benabarre A, Reinares
M, Gasto C.
Bipolar II disorder and comorbidity.
Compr Psychiatry 2000 Sep-Oct;41(5):339-43
"The validity and reliability
of the diagnosis of bipolar II disorder has been questioned by means of comorbidity
with nonaffective disorders, including substance abuse, personality disorders,
and anxiety disorders. This study examined the comorbid diagnosis of a sample
of bipolar II patients, comparing patients with comorbidity and those with "pure"
bipolar II disorder. Forty Research Diagnostic Criteria (RDC) bipolar II patients
were assessed by means of the Schedule for Affective Disorders and Schizophrenia,
Lifetime Version (SADS-L) and Structured Clinical Interview for DSM-III-R axis
I (SCID-II) for personality disorders. Patients fulfilling RDC criteria for any
psychiatric disorder (except personality disorders) or DSM-IV criteria for any
personality disorder were compared with patients without comorbidity. For practical
reasons, cyclothymia was not considered as a comorbid diagnosis. Half of the sample
had lifetime comorbidity with other psychiatric disorders, mainly personality
disorders (33%), substance abuse or dependence (21%), and anxiety disorders (8%).
However, only the rates of suicidal ideation (74% v 24%, chi square [chi2] = 9.03,
P = .003) and suicide attempts (45% v 5%, chi2 = 8.53, P = .003) were significantly
different between patients with and without comorbidity. In summary, although
the rates of comorbidity are relatively high in bipolar II disorder, most clinical
and course variables are strikingly similar in patients with and without comorbidity
except for suicidal behavior, suggesting that comorbidity does not reduce the
validity of the diagnosis of bipolar II disorder." [Abstract]
E, Sax KW, Keck PE Jr, McElroy SL, Sorter MT, McConville BJ, Strakowski SM.
Twelve-month outcome in bipolar patients with and without personality
J Clin Psychiatry 2000 Feb;61(2):134-9
We studied the 12-month course of illness after hospitalization for patients with
a DSM-III-R diagnosis of bipolar disorder, manic or mixed episode, to identify
the impact of a co-occurring personality disorder on measures of outcome. METHOD:
Fifty-nine patients with bipolar disorder hospitalized for the treatment of a
manic or mixed episode were recruited. Diagnostic, symptomatic, and functional
evaluations were obtained at the index hospitalization. Personality disorders
were assessed using the Structured Clinical Interview for DSM-III-R, personality
disorders version (SCID-II). Patients were then reevaluated at 2, 6, and 12 months
after discharge to assess syndromic, symptomatic, and functional recovery. Factors
associated with outcome were identified using multivariate analyses. RESULTS:
Survival analyses showed that in the 12-month follow-up period, subjects with
bipolar disorder and co-occurring personality disorder were significantly less
likely to achieve recovery. Logistic regression analyses indicated that both a
diagnosis of personality disorder and noncompliance with treatment were significantly
associated with lack of syndromic recovery. CONCLUSION: Co-occurring personality
disorders in patients with bipolar disorder are associated with poor outcome after
hospitalization for mania." [Abstract]
TE, Biederman J, Wozniak J, Gunawardene S, Wong J, Monuteaux M.
adults with attention-deficit/hyperactivity disorder be distinguished from those
with comorbid bipolar disorder? Findings from a sample of clinically referred
Biol Psychiatry. 2003 Jul 1;54(1):1-8.
Despite data describing the overlap of attention deficit hyperactivity disorder
(ADHD) and bipolar disorder (BPD) in youth, little is known about adults with
these co-occurring disorders. We now evaluate the clinical characteristics of
referred adults with (n = 24) and without BPD (n = 27). METHODS: Referred adults
to clinical trials of ADHD were evaluated by psychiatric evaluation using DSM-IV
criteria. Structured psychiatric interviews were used to systematically assess
adult and childhood disorders. RESULTS: The vast majority of patients with ADHD
plus BPD had bipolar II disorder (88%). Adults with ADHD plus BPD had higher rates
of the combined subtype of ADHD compared to ADHD without BPD (chi(2) = 8.7, p
=.003), a greater number of DSM-IV ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0;
t = -3.4, p <.01), more attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/-
2.1; t = -2.5, p <.02; trend), poorer global functioning (47 +/- 5.9 and 52
+/- 7.4, t = 2.6, p <.02; trend), and additional comorbid psychiatric disorders
(3.7 +/- 2.5 and 2.0 +/- 1.9; t = -2.9, p <.01). CONCLUSIONS: These results
suggest that adults with ADHD plus BPD have prototypic symptoms of both disorders,
suggesting that both disorders are present and are distinguishable clinically."
G, Akiskal HS, Toni C, Simonini E, Gemignani A.
The temporal relationship
between anxiety disorders and (hypo)mania: a retrospective examination of 63 panic,
social phobic and obsessive-compulsive patients with comorbid bipolar disorder.
J Affect Disord 2001 Dec;67(1-3):199-206
"BACKGROUND: The relationship
between anxiety and depressive disorders has been conventionally limited to unipolar
depression. Recent studies from both clinical and epidemiologic samples have revealed
intriguing associations between anxiety and bipolar (mainly bipolar II) disorders.
The present report examines the temporal sequence of hypomania to panic (PD),
obsessive-compulsive (OCD) and social phobic (SP) disorders. METHODS: Specialty-trained
clinicians retrospectively evaluated the foregoing relationships in 63 patients
meeting the DSM-III-R diagnosis for PD, OCD and SP with lifetime comorbidity with
bipolar disorders (87% bipolar II). Structured interviews were used. RESULTS:
In nearly all cases, SP chronologically preceded hypomanic episodes and disappeared
when the latter episodes supervened. By contrast, PD and OCD symptomatology, even
when preceding hypomanic episodes, often persisted during such episodes; more
provocatively, nearly a third of all onsets of panic attacks were during hypomania.
LIMITATIONS: Assessing temporal relationships between hypomania and specific anxiety
disorders on a retrospective basis is, at best, of unknown reliability. The related
difficulty of ascertaining the extent to which past antidepressant treatment of
anxiety disorders could explain the anxiety-bipolar II comorbidity represents
another major limitation. CONCLUSIONS: Different temporal relationships characterized
the occurrence of hypomania in individual anxiety disorder subtypes. Some anxiety
disorders (notably SP, and to some extent OCD) seem to lie on a broad affective
continuum of inhibitory restraint vs. disinhibited hypomania. By contrast, and
more tentatively, PD in the context of bipolar disorder, might be a reflection
of a dysphoric manic or mixed hypomanic symptomatology. The foregoing suggestions
do not even begin to exhaust the realm of possibilities. The pattern of complex
relationships among these disorders would certainly require better designed prospective
RC, Stang P, Wittchen HU, Stein M, Walters EE.
between social phobia and mood disorders in the US National Comorbidity Survey.
Psychol Med 1999 May;29(3):555-67
"BACKGROUND: General population data
were used to study co-morbidities between lifetime social phobia and mood disorders.
METHODS: Data come from the US National Comorbidity Survey (NCS). RESULTS: Strong
associations exist between lifetime social phobia and major depressive disorder
(odds ratio 2.9), dysthymia (2.7) and bipolar disorder (5.9). Odds ratios increase
in magnitude with number of social fears. Reported age of onset is earlier for
social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary
social phobia predicts subsequent onset of mood disorders, with population attributable
risk proportions of 10-15%. Social phobia is also associated with severity and
persistence of co-morbid mood disorders. CONCLUSIONS: Social phobia is a commonly
occurring, chronic and seriously impairing disorder that is seldom treated unless
it occurs in conjunction with another co-morbid condition. The adverse consequences
of social phobia include increased risk of onset, severity and course of subsequent
mood disorders. Early outreach and treatment of primary social phobia might not
only reduce the prevalence of this disorder itself, but also the subsequent onset
of mood disorders." [Abstract]
Carter TD, Mundo E, Parikh SV, Kennedy JL.
age at onset as a risk factor for poor outcome of bipolar disorder.
Psychiatr Res. 2003 Jul-Aug;37(4):297-303.
"The primary aim of our study
was to investigate the effect of the age at onset (AAO) of Bipolar Disorder (BP)
on the clinical course of the illness. We studied 320 subjects with a diagnosis
of BP I or BP II who had been previously recruited for a genetic research protocol.
All subjects gave their informed consent to participate in the study. Each subject
was interviewed using the SCID I. The main clinical variables were compared between
subjects with early (</=18 years) and later (>/=18 years) age at onset of
BP (chi square tests and t-tests for independent samples). In addition, a logistic
regression analysis was applied to the variables that were significantly related
to earlier onset of BP in the exploratory analyses. We found a significantly earlier
AAO in subjects with anxiety disorders (t=2.44, P=0.015) and rapid cycling course
(t=3.16, P=0.002). When we compared a number of clinical characteristics between
early and later onset of BP, subjects with early AAO had more frequent suicidal
ideation/attempts (chi(2)=12.12, P=0.002), Axis I comorbidity (chi(2)=8.12, P=0.004),
substance use disorders (chi(2)=5.45, P=0.019) and rapid cycling course (chi(2)=9.87,
P=0.002). The Odds Ratios associated with these variables were: 1.407 (suicide
ideation), 1.646 (Axis I comorbidity), 1.468 (substance abuse), and 2.082 (rapid
cycling course). Overall, these results suggest a role of early AAO as a significant
predictor of poor outcome in BP and, if replicated, they may have important clinical
Rossi A, Marinangeli MG, Butti G, Scinto A, Di Cicco L,
Kalyvoka A, Petruzzi C.
Personality disorders in bipolar and depressive
J Affect Disord 2001 Jun;65(1):3-8
association of mood disorders with personality disorders (PDs) is relevant from
a clinical, therapeutic and prognostic point of view. To examine this issue, we
compared the prevalence of DSM-III-R personality disorders assessed with SCID-II
in patients with depressive (n = 117) and bipolar (n = 71) disorders both recovered
from a major depressive index episode that needed hospital admission. PDs prevalence
and comorbidity with axis I were calculated. Avoidant PD (31.6%) (O.R. = 1.7,
C.I. = 1.06-2.9. P < 0.01), borderline PD (30.8%) and obsessive-compulsive
PD (30.8%) were the most prevalent axis II diagnoses among patients with depressive
disorder. In bipolar disorder group, patients showed more frequently obsessive-compulsive
PD (32.4%), followed by borderline PD (29.6%) and avoidant PD (19.7%). Avoidant
PD showed a trend toward being significantly more prevalent among depressives
(P < 0.07). A different pattern of PDs emerges between depressive and bipolar
NC, Du Fort GG, Cervantes P.
Prevalence, clinical correlates, and
treatment of migraine in bipolar disorder.
"OBJECTIVE: To investigate the prevalence, clinical correlates,
and treatment of migraine in bipolar disorder. BACKGROUND: The relationship between
migraine and mood disorders has been of long-standing interest to researchers
and clinicians. Although a strong association has been demonstrated consistently
for migraine and major depression, there has been less systematic research on
the links between migraine and bipolar disorder. METHODS: A migraine questionnaire
(based on International Headache Society criteria) was administered to 108 outpatients
with bipolar disorder. Information on the clinical course of bipolar illness was
also collected. RESULTS: The overall lifetime prevalence of migraine was 39.8%
(43.8% among women and 31.4% among men). In the subgroup of patients with bipolar
II disorder, the lifetime prevalence of migraine was 64.7%. The bipolar with migraine
group was younger, tended to be more educated, was more likely to be employed
or studying, and had fewer psychiatric hospitalizations. Their initial presentation
for psychiatric treatment was more often for symptoms of depression, rather than
hypomania or mania. They were more likely to have a family history of migraine
and psychiatric disorders, and a greater number of affected relatives. They were
less likely to use mood stabilizers, and more likely to use atypical antidepressants.
Migraine was assessed by a neurologist in only 16% of affected patients. The prevalence
of the use of specific antimigraine medications (triptans) was 27.9%. CONCLUSIONS:
This study confirms the higher prevalence of migraine among those with bipolar
disorder compared to the general population. Migraine in patients with bipolar
disorder is underdiagnosed and undertreated. Bipolar disorder with migraine is
associated with differences in the clinical course of bipolar disorder, and may
represent a subtype of bipolar disorder." [Abstract]
Fasmer OB, Oedegaard KJ.
of patients with major affective disorders and comorbid migraine.
J Biol Psychiatry. 2001 Jul;2(3):149-55.
"The present study was undertaken
to examine the clinical characteristics of patients with major affective disorders
and comorbid migraine. Patients (n = 102) with an index episode of either major
depression or mania were interviewed with a semi-structured interview based partly
on DSM-IV criteria and partly on Akiskal's criteria for affective temperaments.
Compared to the patients without migraine (n = 49), the patients with comorbid
migraine (n = 53) had a higher frequency of bipolar II disorder (43% vs. 10%),
a lower frequency of bipolar I disorder (11% vs. 33%), an approximately equal
frequency of unipolar depressive disorder (45% vs. 57%) and a higher frequency
of affective temperaments (45% vs. 22%). The migraine patients also had a greater
number of anxiety disorders (3.0 vs. 1.9) and a higher frequency of panic disorder
and agoraphobia. Gender distribution, age, age at onset of first affective episode,
number of previous episodes and symptoms during depressive episodes were similar
in both groups. Based on these findings it is suggested that the presence of migraine
may be used to delineate a distinct subgroup of the major affective disorders."
The prevalence of migraine
in patients with bipolar and unipolar affective disorders.
Cephalalgia 2001 Nov;21(9):894-9
"There is a well-known association between
migraine and affective disorders, but the information is sparse concerning the
prevalence of migraine in subgroups of the affective disorders. The present study
was undertaken to investigate the prevalence of migraine in unipolar depressive,
bipolar I and bipolar II disorders. Patients with major affective disorders (n
= 62), consecutively admitted to an open psychiatric ward, were examined with
a semi-structured interview based on DSM-IV diagnostic criteria, combined with
separate criteria for affective temperaments. Diagnosis of unipolar and bipolar
I disorders followed the DSM-IV criteria, while bipolar II disorder encompassed
patients with either discrete hypomanic episodes or a cyclothymic temperament.
Migraine was diagnosed according to IHS-criteria. Symptoms of migraine were found
to be common in these patients, both in those with unipolar depression (46% prevalence
of migraine) and in those with bipolar disorders (44% prevalence). Among the bipolar
patients there was, however, a striking difference between the two diagnostic
subgroups, with a prevalence of 77% in the bipolar II group compared with 14%
in the bipolar I group (P = 0.001). These results support the contention that
bipolar I and II are biologically separate disorders and point to the possibility
of using the association of bipolar II disorder with migraine to study both the
pathophysiology and the genetics of this affective disorder." [Abstract]
T, Romans S, Silverstone T.
Prevalence of migraine in bipolar disorder.
J Affect Disord 1999 Jan-Mar;52(1-3):239-41
"BACKGROUND: This study was
undertaken to estimate the prevalence of migraine in people suffering from bipolar
affective disorder. METHODS: a headache questionnaire incorporating the newly
introduced International Headache Society (IHS) criteria was given to 117 patients
on the Dunedin Bipolar Research Register. RESULTS: a total of 81 (69%) completed
the questionnaire, out of which 21 (25.9%) reported migraine headaches. 25% of
bipolar men and 27% of bipolar women suffered from migraine. CONCLUSIONS: these
rates are higher than those reported in the general population with the rate for
bipolar men being almost five-times higher than expected. An increased risk of
suffering form migraine was particularly noted in bipolar patients with an early
onset of the disorder. This may represent a more severe form of bipolar affective
Mahmood T, Silverstone T, Connor R, Herbison P.
Sumatriptan challenge in bipolar patients with and without migraine: a neuroendocrine
study of 5-HT1D receptor function.
Int Clin Psychopharmacol
"An association between bipolar disorder and migraine
has been lately recognized and an abnormality of central serotonergic function
is suggested as the underlying neurophysiological disturbance. To examine the
role of serotonin in bipolar disorder and migraine, we used the neuroendocrine
challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological
probe. We studied nine bipolar patients with migraine, nine bipolar patients without
it, seven migraine patients, and nine matched normal controls. A post-hoc analysis
showed subsensitivity of serotonergic function, reflected in a blunted growth
hormone response to sumatriptan challenge in bipolar patients who also suffered
from migraine." [Abstract]
GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT.
symptoms assessed in longitudinal, prospective follow-up of a cohort of patients
with bipolar disorder.
Bipolar Disord. 2003 Oct;5(5):349-55.
Many patients with bipolar disorder (BD) do not regain full function following
an acute illness episode, but the extent to which this impairment is the result
of persistent symptoms has not been well established. This study examined factors
associated with persistent subsyndromal symptoms in a well characterized group
of BD patients who were prospectively followed for an average of 3 years. METHODS:
Detailed life charting data from 138 patients with BD were reviewed. Patients
were categorized into euthymic, subsyndromal or syndromal groups according to
the clinical state during their most recent year of follow-up. The three groups
were then examined with respect to comorbidity, function and treatment received.
RESULTS: Patients with subsyndromal symptoms had high rates of comorbid anxiety
disorders, and were more likely to have increased rates of eating disorders as
well. Patients with subsyndromal symptoms had lower global assessment of function
(GAF) scores than euthymic patients, and had as many clinic contacts and medication
trials as patients with full episodes of illness. CONCLUSIONS: Persistent subsyndromal
symptoms in BD patients are associated with high rates of comorbidity that is
important to recognize and treat in order to optimize mood and functioning."
JL, Silverstone JT, Mann JI, Williams SM, Romans SE.
of overweight and obesity in bipolar patients.
J Clin Psychiatry
"BACKGROUND: Patients who receive pharmacologic
treatment for bipolar illness frequently gain weight. This study evaluated the
prevalence of overweight and obesity in an unselected group of bipolar patients
and matched reference subjects. METHOD: The prevalence of overweight, obesity,
and central adiposity was evaluated in 89 euthymic bipolar (DSM-IV) patients and
445 reference subjects, matched for age and sex, using a cross-sectional study
design. RESULTS: Female patients were more often overweight and obese than female
reference subjects (chi2 = 9.18, df = 2, p = .01). The frequency of overweight
was similar in male patients and male reference subjects, but male patients were
more likely to be obese. Patients were more centrally obese than the general population
in women (chi2 = 32.21, df = 1, p = <.001) and in men (chi2= 8.81, df = 1,
p = .003). Patients treated with antipsychotic drugs were more obese than patients
not receiving these drugs (chi2= 4.7, df = 1, p = .03). CONCLUSION: Body fat is
more centrally distributed in pharmacologically treated bipolar patients than
in matched population controls. Obesity is more prevalent in patients than in
the general population. Obesity prevalence is clearly related to the administration
of antipsychotic drugs." [Abstract]
A, Kupfer DJ, Houck PR, Novick DM, Frank E.
Obesity as a correlate
of outcome in patients with bipolar I disorder.
Am J Psychiatry.
"OBJECTIVE: This study sought to evaluate the relationship
of obesity to demographic and clinical characteristics and treatment outcome in
a group of 175 patients with bipolar I disorder who were treated for an acute
affective episode and followed through a period of maintenance treatment. METHOD:
Data were from participants entering the Maintenance Therapies for Bipolar Disorder
protocol between 1991 and 2000. Analyses focused on differences in baseline demographic
and clinical characteristics and in treatment outcomes between obese and nonobese
patients. RESULTS: A total of 35.4% of the patients met criteria for obesity.
Significant differences between the obese and nonobese patients were observed
for years of education, numbers of previous depressive and manic episodes, baseline
scores on the Hamilton Rating Scale for Depression, and durations of the acute
episode. A Kaplan-Meier survival analysis indicated a significantly shorter time
to recurrence during the maintenance phase among obese patients. The number of
patients experiencing a depressive recurrence was significantly higher in the
obese than in the nonobese group. CONCLUSIONS: Obesity is correlated with a poorer
outcome in patients with bipolar I disorder. Preventing and treating obesity in
bipolar disorder patients could decrease the morbidity and mortality related to
physical illness, enhance psychological well-being, and possibly improve the course
of bipolar illness. Weight-control interventions specifically designed for patients
with bipolar illness should be developed, tested, and integrated into the routine
care provided for these patients." [Abstract]
Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque
C, Patronelli A, Vignoli S, Bemi E.
The high prevalence of "soft"
bipolar (II) features in atypical depression.
"Seventy-two percent of 86 major depressive
patients with atypical features as defined by the DSM-IV and evaluated systematically
were found to meet our criteria for bipolar II and related "soft" bipolar
disorders; nearly 60% had antecedent cyclothymic or hyperthymic temperaments.
The family history for bipolar disorder validated these clinical findings. Even
if we limit the diagnosis of bipolar II to the official DSM-IV threshold of 4
days of hypomania, 32.6% of atypical depressives in our sample would meet this
conservative threshold, a rate that is three times higher than the estimates of
bipolarity among atypical depressives in the literature. By definition, mood reactivity
was present in all patients, while interpersonal sensitivity occurred in 94%.
Lifetime comorbidity rates were as follows: social phobia 30%, body dysmorphic
disorder 42%, obsessive-compulsive disorder 20%, and panic disorder (agoraphobia)
64%. Both cluster A (anxious personality) and cluster B (e.g., borderline and
histrionic) personality disorders were highly prevalent. These data suggest that
the "atypicality" of depression is favored by affective temperamental
dysregulation and anxiety comorbidity, clinically manifesting in a mood disorder
subtype that is preponderantly in the realm of bipolar II. In the present sample,
only 28% were strictly unipolar and characterized by avoidant and social phobic
features, without histrionic traits." [Abstract]
LV, Nilsson FM.
Increased risk of developing dementia in patients
with major affective disorders compared to patients with other medical illnesses.
Affect Disord. 2003 Feb;73(3):261-9.
"BACKGROUND: The association between
affective disorder and subsequent dementia is unclear. Our aim was to investigate
whether patients with unipolar or bipolar affective disorder have an increased
risk of developing dementia compared to patients with other chronic illnesses.
METHOD: By linkage of the psychiatric and somatic nation-wide registers of all
hospitalised patients in Denmark, 2007 patients with mania, 11741 patients with
depression, 81380 patients with osteoarthritis and 69149 patients with diabetes
were identified according to diagnosis at first-ever discharge from a psychiatric
or somatic hospital between 1 January 1977 and 31 December 1993. The risk of receiving
a diagnosis of dementia on subsequent re-admission was estimated with the use
of survival analyses. RESULTS: Patients with unipolar or bipolar affective disorder
had a greater risk of receiving a diagnosis of dementia than patients with osteoarthritis
or diabetes. Differences in age and gender and the effect of alcohol- or drug-abuse
did not explain these associations. CONCLUSION: Patients with unipolar or bipolar
affective disorder seem to have an increased risk of developing dementia compared
to patients with other illnesses. LIMITATION: The study includes only patients
who have been hospitalised at least once. CLINICAL RELEVANCE: Patients with unipolar
or bipolar affective disorder may be at increased risk of developing dementia."
M, Slaney C, Garnham J, Alda M.
Clinical features of bipolar disorder
with and without comorbid diabetes mellitus.
Can J Psychiatry.
"OBJECTIVE: Several papers have reported higher
prevalence of diabetes mellitus (DM) type 2 in patients suffering from bipolar
disorder (BD). The possible links between these 2 disorders include treatment,
lifestyle, alterations in signal transduction, and possibly, a genetic link. To
study this relation more closely, we investigated whether there are any differences
in the clinical characteristics of BD patients with and without DM. METHOD: We
compared the clinical data of 26 diabetic and 196 nondiabetic subjects from The
Maritime Bipolar Registry. Subjects were aged 15 to 82 years, with psychiatric
diagnoses of BD I (n = 151), BD II (n = 65), and BD not otherwise specified (n
= 6). The registry included basic demographic data and details on the clinical
course of bipolar illness, its treatment, and physical comorbidity. In a subsequent
analysis using logistic regression, we examined the variables showing differences
between groups, with diabetes as an outcome variable. RESULTS: The prevalence
of DM in our sample was 11.7% (n = 26). Diabetic patients were significantly older
than nondiabetic patients (P < 0.001), had higher rates of rapid cycling (P
= 0.02) and chronic course of BD (P = 0.006), scored lower on the Global Assessment
of Functioning Scale (P = 0.01), were more often on disability for BD (P <
0.001), and had higher body mass index (P < 0.001) and increased frequency
of hypertension (P = 0.003). Lifetime history of treatment with antipsychotics
was not significantly associated with an elevated risk of diabetes (P = 0.16);
however, the data showed a trend toward more frequent use of antipsychotic medication
among diabetic subjects. CONCLUSIONS: Our findings suggest that the diagnosis
of DM in BD patients is relevant for their prognosis and outcome." [Abstract]
Nilsson FM, Kessing LV, Bolwig TG.
the increased risk of developing late-onset epilepsy for patients with major affective
J Affect Disord. 2003 Sep;76(1-3):39-48.
Based on register data we wanted to investigate whether patients with a diagnosis
of affective disorder are at increased risk of developing epilepsy compared to
other medically ill control groups. METHODS: By linkage of public hospital registers
covering the whole of Denmark from 1977 to 1993, using ICD-8 diagnoses, three
study cohorts were identified: Patients with first affective disorder episodes
(mania and depression), patients with first osteoarthritis and patients with first
diabetes discharge. Time to first diagnosis of epilepsy was estimated with the
use of survival analysis. RESULTS: A total of 164,227 patients entered the study
base: 13,748 patients with mania or depression, 81,380 patients with osteoarthritis
and 69,149 patients with diabetes. The risk of getting a diagnosis of epilepsy
was increased for patients with affective disorder compared with the risk for
the control groups. However, the increased risk seemed to be due to the effect
of comorbid alcohol or drug abuse and not to the effect of the affective illness
itself. LIMITATIONS: The results only apply to hospitalised patients. Diagnoses
are not validated for research purposes. CONCLUSION: Patients with a diagnosis
of affective disorder have an increased risk of developing epilepsy in later life.
In patients with affective disorder, comorbid alcoholism/drug abuse seriously
increased the risk of a subsequent diagnosis of epilepsy." [Abstract]