The Anxiety-Bipolar Connection

A MEDLINE search by Ivan Goldberg, MD

1: Aust N Z J Psychiatry. 2003 Jun;37(3):355-61.

Awareness of illness in patients with bipolar I disorder with or without
comorbid anxiety disorders.

Pini S, Dell’Osso L, Amador XF, Mastrocinque C, Saettoni M, Cassano GB.

Department of Psychiatry, Pharmacology, Neurobiology and Bio-technology,
University of Pisa, via Roma 67, 56100 Pisa, Italy.

BACKGROUND: The present study examined whether specific types of comorbid
anxiety disorders, namely panic disorder (PD), social phobia (SP) and
obsessive-compulsive disorder (OCD) are differentially associated with course
variables and insight into bipolar illness. METHOD: The sample consisted of 151
consecutively hospitalized patients with bipolar I disorder. They were assessed
in the week prior to discharge using the Structured Clinical Interview for
DSM-III-R (SCID-P), the Brief Psychiatric Rating Scale (BPRS), the Global
Assessment of Functioning Scale (GAF) and the Hopkins Symptom Checklist
(HSCL-90). Level of insight was assessed with the Scale to assess Unawareness of
Mental Disorders (SUMD). RESULTS: Of the 151 bipolar subjects, 92 had no PD, SP
and OCD comorbidity, 35 had PD and 24 had SP and/or OCD. The three groups
differed significantly on the current awareness of illness and treatment
response scores and the retrospective awareness of illness and treatment
response scores. Post-hoc analyses revealed that, compared with bipolar patients
without PD/SD/OCD and those with comorbid PD, patients with comorbid SP and/or
OCD had better insight on current awareness of illness, current awareness of
treatment response, retrospective awareness of illness and retrospective
awareness of treatment response. The regression analysis showed that the
presence of no panic type anxiety comorbidity was a predictor of good insight.
CONCLUSIONS: These data indicate the value of identifying comorbid anxiety
disorders in patients with bipolar illness. The results could be interpreted as
evidence of discrete disorders within the bipolar spectrum, one that is
characterized by, among other things, SP and/or OCD with good insight, another
characterized by PD with poor insight.

PMID: 12780476 [PubMed – indexed for MEDLINE]


2: J Clin Psychiatry. 2003 Mar;64(3):331-5.

Anxiety disorders in 318 bipolar patients: prevalence and impact on illness
severity and response to mood stabilizer.

Henry C, Van den Bulke D, Bellivier F, Etain B, Rouillon F, Leboyer M.

Department of Adult Psychiatry, Charles Perrens Hospital, and INSERM U-394,
Integrative Neurobiology, Bordeaux, France.

OBJECTIVE: 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.

Publication Types:
Multicenter Study

PMID: 12716276 [PubMed – indexed for MEDLINE]


3: J Affect Disord. 2003 Jan;73(1-2):19-32.

The comparative clinical phenotype and long term longitudinal episode course of
bipolar I and II: a clinical spectrum or distinct disorders?

Judd LL, Akiskal HS, Schettler PJ, Coryell W, Maser J, Rice JA, Solomon DA,
Keller MB.

National Institute of Mental Health Collaborative Program on the Psychobiology
of Depression-Clinical Studies, USA.

BACKGROUND: 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.

PMID: 12507734 [PubMed – indexed for MEDLINE]


4: Psychiatr Clin North Am. 2002 Dec;25(4):757-74.

The social anxiety spectrum.

Schneier FR, Blanco C, Antia SX, Liebowitz MR.

Anxiety Disorders Clinic, New York State Psychiatric Institute, 1051 Riverside
Drive, Unit 69, New York, NY 10032, USA.

Social anxiety disorder is well suited to the spectrum concept because it has
trait-like qualities of early onset, chronicity, and no empirically derived
threshold that demarcates normal from clinically significant trait social
anxiety. Social anxiety disorder has been shown to respond to relatively
specific pharmacologic and cognitive-behavioral therapies, which makes
identification of other conditions that may lie on the social anxiety disorder
spectrum important because of possible treatment implications. Biologic markers
associated with social anxiety disorder also may be shared by similar but
nonidentical traits, such as behavioral inhibition and detachment. Clarification
of the trait spectrums associated with specific biologic systems offers an
opportunity for improving the understanding of the origin of these conditions.
Strong evidence exists that at least some forms of shyness, avoidant personality
disorder, and selective mutism lie on a social anxiety disorder spectrum. For
several other disorders that share a prominent focus on social comparison,
significant subgroups of patients seem to have features of social anxiety
disorder. These disorders include major depression (especially the atypical
subtype), body dysmorphic disorder, and eating disorders. Several other
disorders marked by social dysfunction or inhibition, including substance use
disorders (especially alcoholism), paranoid disorder, bipolar disorder, autism,
and Asperger’s disorder, also may show some overlap with social anxiety disorder
features (e.g., social anxiety as a cause or complication of substance abuse,
social avoidance in paranoid disorder, social disinhibiton in bipolar disorder,
and social communication deficits in autism and Asperger’s disorder). Social
anxiety disorder also is associated with other anxiety disorders in general and
other phobias in particular. In respect to traits, a growing body of evidence
links behavioral inhibition to the unfamiliar to a social anxiety disorder
spectrum with some specificity. Biologic measures of dopamine system
hypoactivity have been linked to social anxiety disorder, trait detachment, and
general deficits in reward and incentive function. It remains to be clarified,
however, whether this brain system function is best characterized by a social
anxiety disorder spectrum or some variant that incorporates social reward
deficits or social avoidance behavior. Social anxiety disorder, shyness, and
behavioral inhibition all seem to have a genetic component, but more research is
needed to attempt to identify a more specifically heritable temperament
associated with these conditions. Finally, the emergent concept of a social
anxiety spectrum needs maturation. Although the notion of a single social
anxiety disorder spectrum currently has some clinical use, the authors believe
that exclusive focus on the notion of a single continuum with two extremes–from
social disinhibition in mania to the most severe form of social anxiety,
avoidant personality disorder–is premature and limiting in respect to etiologic
research. An alternative approach is to conceptualize multiple, probably
overlapping spectra in this area of social psychopathology. Individual
dimensions might be based on various core phenomenologic, cognitive, or biologic
characteristics. A bottom-up biologic approach holds promise for identifying
spectra with a common etiology that might respond to specific treatments. Taking
a pluralistic view of the concept of spectrum at this stage may help accelerate
our understanding of social anxiety and related disorders.

Publication Types:
Review, Tutorial

PMID: 12462859 [PubMed – indexed for MEDLINE]


5: Psychopathology. 2002 Jul-Aug;35(4):203-9.

Comorbidity of anxiety disorder among patients with bipolar I disorder in

Tamam L, Ozpoyraz N.

Department of Psychiatry, Faculty of Medicine, Cukurova University, Adana,

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. Copyright 2002 S. Karger AG, Basel

PMID: 12239436 [PubMed – indexed for MEDLINE]


6: J Affect Disord. 2002 Feb;68(1):33-9.

Alcohol abuse in social phobic patients: is there a bipolar connection?

Perugi G, Frare F, Madaro D, Maremmani I, Akiskal HS.

Department of Psychiatry, University of Pisa, Via Roma 67, 56100 Pisa, Italy.

BACKGROUND: Epidemiological and clinical studies have reported the frequent
co-occurrence of social phobia (SP) and alcohol use disorders. Patients with SP
often use alcohol to cope with the social situations they fear, and to lessen
anticipatory anxiety, behavioral inhibition, and phobic avoidance. We
investigated whether the presence of lifetime comorbidity with alcohol abuse was
associated with significant differences as regards demographic and clinical
features, family history and pattern of comorbidity in a large clinical sample
of SP outpatients. METHOD: The sample comprised 153 outpatients who met
DSM-III-R diagnostic criteria for SP. Demographic, family history and course
characteristics were investigated by a semi-structured interview. Social phobic
symptoms and the severity of the illness have been assessed by the Liebowitz
Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating
Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL
90). RESULTS: Thirty-four patients (22.2%) had a past or current history of
alcohol abuse for at least 1 year. There were no significant differences between
these patients and those without a history of alcohol abuse, as regards
demographic features and lifetime comorbidity with major depression and other
anxiety disorders. Bipolar disorder type II was found almost exclusively among
patients with alcohol abuse, as well as family history for bipolar disorders.
LIMITATIONS: Retrospective study. CONCLUSIONS: Our data indicate a strong
relationship between bipolar II disorder and alcohol abuse comorbidity in
patients with SP. The socializing and disinhibiting effect that many social
phobics report might be mediated by mood elation induced by alcohol. The
presence of bipolar diathesis in patients presenting with social anxiety might
explain their increased susceptibility to alcohol, as they might undertake
alcohol abuse as an attempt to overcome social difficulties.

PMID: 11869780 [PubMed – indexed for MEDLINE]


7: J Affect Disord. 2002 Feb;68(1):1-23.

The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and
treatment issues.

Freeman MP, Freeman SA, McElroy SL.

University of Cincinnati College of Medicine, Biological Psychiatry Program,
Department of Psychiatry, P.O. Box 670559, 231 Bethesda Avenue, Cincinnati, OH
45267-0559, USA.

BACKGROUND: Although symptoms of anxiety as well as anxiety disorders commonly
occur in patients with bipolar disorder, the pathophysiologic, theoretical, and
clinical significance of their co-occurrence has not been well studied. METHODS:
The epidemiological and clinical studies that have assessed the overlap of
bipolar and anxiety disorders are reviewed, with focus on panic disorder and
obsessive-compulsive disorder (OCD), and to a lesser extent, social phobia and
post-traumatic stress disorder. Potential neural mechanism and treatment
response data are also reviewed. RESULTS: A growing number of epidemiological
studies have found that bipolar disorder significantly co-occurs with anxiety
disorders at rates that are higher than those in the general population.
Clinical studies have also demonstrated high comorbidity between bipolar
disorder and panic disorder, OCD, social phobia, and post-traumatic stress
disorder. Psychobiological mechanisms that may account for these high
comorbidity rates likely involve a complicated interplay among various
neurotransmitter systems, particularly norepinephrine, dopamine,
gamma-aminobutyric acid (GABA), and serotonin. The second-messenger system
constituent, inositol, may also be involved. Little controlled data are
available regarding the treatment of bipolar disorder complicated by an anxiety
disorder. However, adequate mood stabilization should be achieved before
antidepressants are used to treat residual anxiety symptoms so as to minimize
antidepressant-induced mania or cycling. Moreover, preliminary data suggesting
that certain antimanic agents may have anxiolytic properties (e.g. valproate and
possibly antipsychotics), and that some anxiolytics may not induce mania (e.g.
gabapentin and benzodiazepines other than alprazolam) indicate that these agents
may be particularly useful for anxious bipolar patients. CONCLUSIONS: Comorbid
anxiety symptoms and disorders must be considered when diagnosing and treating
patients with bipolar disorder. Conversely, patients presenting with anxiety
disorders must be assessed for comorbid mood disorders, including bipolar
disorder. Pathophysiological, theoretical, and clinical implications of the
overlap of bipolar and anxiety disorders are discussed.

Publication Types:
Review, Tutorial

PMID: 11869778 [PubMed – indexed for MEDLINE]


8: J Affect Disord. 2001 Dec;67(1-3):199-206.

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.

Perugi G, Akiskal HS, Toni C, Simonini E, Gemignani A.

Institute of Psychiatry, University of Pisa, Via Roma 67, 56100 Pisa, Italy.

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 observations.

PMID: 11869769 [PubMed – indexed for MEDLINE]


9: J Affect Disord. 2001 Dec;67(1-3):175-9.

Anxiety disorders comorbidity in bipolar I, bipolar II and unipolar major
depression: results from a population-based study in Hungary.

Rihmer Z, Szadoczky E, Furedi J, Kiss K, Papp Z.

National Institute for Psychiatry and Neurology, POB 1, Budapest 27, 1281

BACKGROUND: The aim of this study was to analyze the lifetime comorbidity
between DSM-III-R anxiety disorders in separate subgroups of patients with major
depression, bipolar II and bipolar I disorder in a community sample of a
Hungarian population. METHODS: Randomly selected subjects (aged between 18 and
64 years, N=2953) were interviewed by the Diagnostic Interview Schedule (DIS)
which generated DSM-III-R diagnoses. RESULTS: The prevalence of generalized
anxiety disorder, agoraphobia and simple phobia was the highest among bipolar II
patients (20.8, 37.5 and 16.7%, respectively), social phobia was most prevalent
in (nonbipolar) major depression (17.6%), while the rate of panic disorder was
the same in the (nonbipolar) major depressive and bipolar II subgroups (12.4 and
12.5%, respectively). Bipolar I patients showed a relatively low rate of
comorbidity. CONCLUSIONS: The findings support previous results on the
particularly high rate of lifetime comorbidity between anxiety disorders and
unipolar major depression and particularly bipolar II illness. LIMITATIONS:
Underestimation of the prevalence of bipolar II disorder by the diagnostic
methodology used, resulting in a small number of bipolar II cases, lack of
analysis of data by gender, no data on obsessive-compulsive disorder.

PMID: 11869765 [PubMed – indexed for MEDLINE]


10: Compr Psychiatry. 2001 Sep-Oct;42(5):375-81.

Bipolar II and unipolar comorbidity in 153 outpatients with social phobia.

Perugi G, Frare F, Toni C, Mata B, Akiskal HS.

Department of Psychiatry, University of Pisa, Via Roma 67, 56100 Pisa, Italy.

Previous studies on social phobia (SP) have focused largely on comorbidity
between SP and major depression. Less attention has been devoted to the
comorbidity between SP and bipolar disorder. In this retrospective study, we
investigated family history, lifetime comorbidity, and demographic and clinical
characteristics among 153 outpatients who met DSM-III-R diagnostic criteria for
SP. Information regarding axis I diagnoses was obtained using the Structured
Clinical Interview for DSM III-R (SCID-UP-R). Social phobic symptoms and the
severity of the illness were assessed by the Liebowitz Social Anxiety Scale
(LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity
(LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). Fourteen
patients (9.1%) satisfied DSM-III-R criteria for lifetime bipolar disorder not
otherwise specified (NOS) (bipolar II), while 71 (46.4%) had unipolar major
depression and 68 (44.4%) had no lifetime history of major mood disorders.
Comorbid panic disorder/agoraphobia (PDA), obsessive-compulsive disorder (OCD),
and alcohol abuse were reported more frequently in the bipolar group than in the
other two subgroups. Unipolar patients showed higher rates of comordid PDA and
OCD compared with SP patients without mood disorders. Severity and
generalization of the SP symptoms, prevalent interactional anxiety, multiple
comorbidity, and alcohol abuse appeared to be the most relevant consequences of
SP-bipolar coexistence. In a significant minority of cases, protracted social
anxiety may hypothetically have represented, along with inhibited depression,
the dimensional opposite of gregarious hypomania. Copyright 2001 by W.B.
Saunders Company

PMID: 11559864 [PubMed – indexed for MEDLINE]


11: J Psychiatr Res. 1999 Jan-Feb;33(1):53-61.

Depressive comorbidity of panic, social phobic, and obsessive-compulsive
disorders re-examined: is there a bipolar II connection?

Perugi G, Akiskal HS, Ramacciotti S, Nassini S, Toni C, Milanfranchi A, Musetti

Institute of Psychiatry, University of Pisa, Italy.

Utilizing the DSM-III-R schema, we have investigated lifetime comorbidity
between panic disorder with or without agoraphobia (PD), social phobia (SP) and
obsessive-compulsive disorder (OCD) on the one hand, and mood disorder on the
other. Compared with PD, the results for SP and OCD showed significantly higher
numbers of comorbid anxiety and mood disorders. In addition, SP and OCD were
significantly more likely to cooccur with each other than with PD. The
complexity of these comorbid patterns is underscored by the finding of
significantly higher numbers of anxiety disorders in those with lifetime
comorbidity with bipolar (especially bipolar II) disorder. We conclude that the
comorbidity between anxiety and mood disorders – conventionally conceived as the
relationship between anxiety and unipolar depressive states — might very well
extend into the domain of bipolar spectrum disorders in a subset of these
disorders. Among the latter, the spontaneous or antidepressant-induced switches
into brief disinhibited (hypomanic) behavior can be conceptualized to lie on a
dimensional continuum with the temperamental inhibition (or constraint)
underlying the anxiety disorders under discussion. These findings and
theoretical considerations have important therapeutic implications.

PMID: 10094240 [PubMed – indexed for MEDLINE]


12: Am J Psychiatry. 1999 Mar;156(3):474-6.

Multiple anxiety disorder comorbidity in patients with mood spectrum disorders
with psychotic features.

Cassano GB, Pini S, Saettoni M, Dell’Osso L.

Institute of Psychiatry, School of Medicine, University of Pisa, Italy.

OBJECTIVE: The authors investigated frequencies and clinical correlates of
multiple associations of panic disorder, obsessive-compulsive disorder (OCD),
and social phobia in patients with severe mood disorders. METHOD: Subjects were
77 consecutively hospitalized adults with psychotic symptoms and with a
diagnosis of bipolar I disorder, major depression, or schizoaffective disorder,
bipolar type. Principal diagnosis and comorbidity were assessed by the
Structured Clinical Interview for DSM-III-R-Patient Version. RESULTS: Of the
entire cohort, 33.8% had a single anxiety disorder and 14.3% had two or three
comorbid diagnoses. Patients with multiple comorbidity had significantly higher
scores on the Brief Psychiatric Rating Scale and SCL-90 and abused stimulants
more frequently than did those without anxiety disorders. CONCLUSIONS: Multiple
associations of panic disorder, OCD, and social phobia are not rare among
patients with affective psychoses and are likely to be associated with more
severe psychopathology than is found in patients without anxiety disorders.

PMID: 10080568 [PubMed – indexed for MEDLINE]


13: J Affect Disord. 1998 Sep;50(2-3):203-13.

Social anxiety, hypomania and the bipolar spectrum: data, theory and clinical

Himmelhoch JM.

Department of Psychiatry, University of Pittsburgh School of Medicine,
Pennsylvania, USA.

Reports in the literature indicate a subtle but consistent relationship between
panic and bipolar II disorder. The possible connection between social phobia and
bipolarity is less investigated. When we studied the treatment outcome of 32
social phobic patients administered either the reversible monoamine oxidase
inhibitor (RIMA) meclobomide or the irreversible inhibitor MAOI phenelzine, we
found that eighteen had remission > 50% of their socially anxious symptoms.
Moreover, 14/18 of those improved became hypomanic, according to the Raskin
Mania Scale (RMS) and the Young Mania Scale (YMS) coupled with expert clinical
diagnosis. These findings possibly allude to a relationship of social phobia to
bipolarity. Treatment with RIMA or MAOI exposed these subjects as having an
atypical bipolar syndrome which is part of the bipolar spectrum. We then
compared this special subset of subjects to the 18 socially phobic patients who
failed to respond to RIMA’s or MAOI’s and to 26 patients with generalized
anxiety disorder (GAD). Eleven of the 14 hypomanic responders gave histories of
serious developmental deprivation (anaclisis); only 5/18 social phobics and 3/26
GADs without hypomanic responses had anaclitic histories. The author raises the
possibility that anaclisis may have interacted with the impediment of volition
of uncomplicated bipolar depression to produce social inhibition and anxiety.
Finally, the author upholds the central role of depressive inhibition in bipolar
disorder, which during antidepressant therapy often overshoots in a hypomanic
direction; even in the absence of prior spontaneous hypomania, such
disinhibition should classify this special subset of social phobic patients
within the bipolar spectrum.

PMID: 9858079 [PubMed – indexed for MEDLINE]


14: Aust N Z J Psychiatry. 1998 Feb;32(1):67-72.

Comment in:
Aust N Z J Psychiatry. 1998 Oct;32(5):731.
Aust N Z J Psychiatry. 1999 Dec;33(6):946-7.

The prevalence of comorbid anxiety in schizophrenia, schizoaffective disorder and
bipolar disorder.

Cosoff SJ, Hafner RJ.

Royal Adelaide Hospital, Australia.

OBJECTIVE: The aim of this study to determine the prevalence of anxiety
disorders in publically treated psychiatric inpatients with a DSM-IV diagnosis
of schizophrenia, schizoaffective disorder or bipolar disorder. METHOD: Using
the Structured Clinical Interview for DSM-III-R (SCID), 100 consecutive
inpatients with a psychotic disorder were examined for the presence or absence
of an anxiety disorder. Questionnaire measures of phobias, obsessive-compulsive
and general anxiety symptoms were also applied. RESULTS: The prevalences of
social phobia (17%), obsessive-compulsive disorder (13%) and generalised anxiety
disorder in schizophrenia were relatively high, as were prevalences of
obsessive-compulsive (30%) and panic disorder (15%) in bipolar disorder. The
proportion of subjects with an anxiety disorder (43-45%) was almost identical
across the three psychoses, with some evidence of gender differences. Although
self-ratings of overall psychiatric symptoms were significantly elevated in
those with anxiety disorders, hospital admission rates were not. CONCLUSIONS:
Almost none of those with anxiety disorders were being treated for them,
primarily because the severity of the acute psychotic illness required full
diagnostic and therapeutic attention. Patients were generally discharged as soon
as their psychotic episode was resolved, with little recognition of the presence
of an anxiety disorder. Given that anxiety disorders are relatively responsive
to treatment, greater awareness of their comorbidity with psychosis should yield
worthwhile clinical benefits.

PMID: 9565185 [PubMed – indexed for MEDLINE]


15: Compr Psychiatry. 1998 Mar-Apr;39(2):63-71.

The high prevalence of “soft” bipolar (II) features in atypical depression.

Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A,
Vignoli S, Bemi E.

Institute of Psychiatry, University of Pisa, Italy.

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.

PMID: 9515190 [PubMed – indexed for MEDLINE]


16: Addiction. 1997 Oct;92(10):1289-304.

The life-time rates of three major mood disorders and four major anxiety
disorders in alcoholics and controls.

Schuckit MA, Tipp JE, Bucholz KK, Nurnberger JI Jr, Hesselbrock VM, Crowe RR,
Kramer J.

Department of Psychiatry (116A), Veterans Affairs Medical Center (116A),
University of California, San Diego 92161-2002, USA.

AIMS: While psychiatric symptoms are common in the general population and even
more prevalent in alcoholics, their clinical implications are not clear. The
goal of this study was to establish the life-time rates of several independent
and concurrent mood and anxiety disorders in alcoholics, controls and their
relatives. DESIGN: Structured interviews were administered to alcoholics
entering treatment, their relatives, and controls. SETTING: The study was
carried out in six different centers in the United States as part of the
Collaborative Study on the Genetics of Alcoholism (COGA). PARTICIPANTS: Data
were gathered from 2713 alcohol dependent subjects (probands and their alcoholic
relatives) and 919 controls. MEASUREMENTS: The timeline-based Semi-Structured
Assessment for the Genetics of Alcoholism (SSAGA) interview was administered
face to face by trained, closely supervised interviewers. The life-time rates
for concurrent and independent disorders were determined for three DSM-III-R
major mood and four major anxiety disorders. FINDINGS: Some form of independent
mood disorder was seen during the life-time in slightly fewer alcoholics than
controls (14.0% and 17.1%), but alcoholics did show higher rates of independent
bipolar disorder (2.3% vs. 1.0%). The life-time rate for independent anxiety
disorders was significantly higher in alcoholics than controls (9.4% vs. 3.7%),
with most of the differential related to panic disorder (4.2% vs. 1.0%) and
social phobia (3.2% vs. 1.4%), but no significant group differences for
agoraphobia or obsessive-compulsive disorder. In general, these findings
regarding mood and anxiety disorders were reflected in close relatives.
CONCLUSIONS: The large majority of alcohol-dependent men and women in this
sample did not have any of the independent mood or anxiety disorders evaluated
here. However, there was evidence of enhanced risks among alcoholics for
independent bipolar, panic and social phobic disorders. Studies which do not
distinguish carefully between independent and concurrent mood and anxiety
disorders in alcoholics are likely to report much higher rates of co-morbid
psychiatric disorders than those that distinguish between the two types of

Publication Types:
Multicenter Study

PMID: 9489046 [PubMed – indexed for MEDLINE]


17: J Affect Disord. 1997 Feb;42(2-3):145-53.

Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar
depression and dysthymia.

Pini S, Cassano GB, Simonini E, Savino M, Russo A, Montgomery SA.

Institute of Psychiatry, University of Verona, Ospedale Policlinico, Italy.

Eighty-seven patients with current episode of depression were assessed by the
SCID-P and subdivided in bipolar depressives (N = 24), unipolar depressives (n =
38) and dysthymics (n = 25). Anxiety disorders comorbidity in these three groups
was investigated by means of the SCID-P. Panic disorder comorbidity was found in
36.8% of bipolar depressives, 31.4% of unipolar depressives and 13% of
dysthymics. Prevalence of obsessive-compulsive disorder was 21.1% in bipolars,
14.3% in unipolars and 8.7% in dysthymics. Generalized anxiety disorder resulted
in being much more associated with dysthymia (65.2%) than with bipolar (31.6%)
or unipolar depression (37.1%). Social phobia comorbidity was exhibited mainly
by unipolars (11.4%), while no cases were detected in the bipolar group. Odds
ratios revealed that generalized anxiety disorder is significantly more likely
to co-occur with dysthymia. Panic disorder showed a higher trend to be
associated with bipolar and unipolar depression. Social phobia was more frequent
among unipolar depression.

PMID: 9105956 [PubMed – indexed for MEDLINE]


18: J Affect Disord. 1993 Jul;28(3):155-63.

Affective comorbidity in panic disorder: is there a bipolar connection?

Savino M, Perugi G, Simonini E, Soriani A, Cassano GB, Akiskal HS.

II Psychiatric Clinic, University of Pisa, Italy.

Although theoretical explanations for comorbidity in panic disorder (PD) abound
in the literature, the complex clinical challenges of these patients have been
neglected, especially where panic, obsessive-compulsive and ‘soft’ bipolar
(e.g., hypomanic, cyclothymic and hyperthymic) conditions might co-exist. The
aim of the present study has been to systematically explore the spectrum of
intra-episodic and longitudinal comorbidity of 140 DSM-III-R PD patients–67.1%
of whom concomitantly met the criteria for Agoraphobia–and who were
consecutively admitted to the ambulatory service of the Psychiatric Clinic of
the University of Pisa over a 2-year period. Comorbidity with strictly defined
anxiety disorders–i.e., not explained as mere symptomatic extensions of PD–was
relatively uncommon, and included Simple Phobia (10.7%), Social Phobia (6.4%),
Generalized Anxiety Disorder (3.6%), and Obsessive-Compulsive Disorder (4.2%).
Comorbidity with Major Depression–strictly limited to the melancholic
subtype–occurred in 22.9%. Comorbidity with Bipolar Disorders included 2.1%
with mania, 5% with hypomania, as well as 6.4% with cyclothymia, for a total of
13.5%; an additional 34.3% of PD patients met the criteria for hyperthymic
temperament. We submit that such comorbid patterns are at the root of unwieldy
clinical constructs like ‘atypical depression’ and ‘borderline personality’. The
relationship of panic disorder to other anxious-phobic and depressive states has
been known for some time. Our data extend this relationship to soft bipolar
disorders. Studies from other centers are needed to verify that the proposed new
link is not merely due to referral bias to a tertiary university setting.

PMID: 8408978 [PubMed – indexed for MEDLINE]