Are major depressive disorder and bipolar disorder related? There are
various reasons to think so. For instance, bipolar disorder is sometimes
misdiagnosed as recurrent major depressive disorder. Bipolar disorder and
severe major depression are also known to aggregate in families, and this
overlap appears to be due to genetic factors.
And now still more reason to believe that major depression and bipolar
disorder are related comes from a study conducted by Italian and American
psychiatric researchers. It found that subjects with recurrent major
depression experienced a substantial number of manic/hypomanic symptoms over
The principal author of the study is Giovanni Cassano, M.D., director of
the department of psychiatry, neurobiology, pharmacology, and biotechnology at
the University of Pisa. Results of the study appeared in the July American
Journal of Psychiatry.
Recruited to participate in the study were 117 patients with remitted
recurrent major depression and 106 patients with bipolar I disorder. Patients
in both groups included inpatients and outpatients from nine academic settings
The investigators confirmed all of the subjects' diagnoses with the Mini
International Neuropsychiatric Interview, a brief structured interview
designed to diagnose Axis I disorders and antisocial personality disorder
according to DSM-IV and ICD-10 criteria. The reliability of
this instrument has proven to be excellent in multicenter clinical trials and
in epidemiological and clinical studies.
The subjects were also given the Structured Clinical Interview for the
Spectrum of Mood Disorders. It was developed by Italian and American
psychiatrists, including several of the authors of this study, to assess
subjects' lifetime symptoms, traits, and lifestyles that characterize
threshold and subthreshold mood episodes as well as temperamental features
related to mood dysregulation.
First, the subjects with recurrent major depression reported that they had
experienced a substantial number of manic or hypomanic symptoms over their
"The presence of a significant number of manic/hypomanic items in
patients with recurrent major depression seems to challenge the traditional
dichotomy of unipolar-bipolar disorder and bridges the gap between these two
categories of mood disorders," the researchers stated in their study
Second, in both patients with recurrent major depression and patients with
bipolar I disorder, the number of manic/hypomanic items reported was related
to the number of depressive items reported, suggesting a link between the
And finally, the more manic/hypomanic items that the recurrent major
depression subjects reported, the greater the likelihood that they also
reported having suicidal ideas or paranoid or delusional thoughts, such as"
feeling as if others were causing all of your problems,""
feeling surrounded by hostility," or "everyone is talking
about you," at some point in their lives.
"This latter result," the researchers wrote,"
corroborates the observation that the presence of even mild manic
symptoms may change a depressive presentation into a mixed presentation and
increase the likelihood of psychotic symptoms."
These results imply, said the researchers, that major depression and
bipolar disorder are related and that the psychiatric field "would
benefit from a unitary and continuous approach to the assessment of both
manic/hypomanic and depressive symptoms."
Or as Cassano told Psychiatric News, the results "provide
evidence that a substantial proportion of patients with unipolar depression
experience manic/hypomanic symptoms during their lifetime and that these
symptoms are associated with a more negative prognosis (suicidality, paranoid
ideation). Because this association is similar to the one found in bipolar
patients, we conclude that unipolar and bipolar disorders are not two discrete
entities, but should be considered a unitary phenomenon, to be studied using a
When asked about the clinical implications of the results, Cassano said,"
The assessment of manic-hypomanic symptoms in so-called unipolar
patients is probably important in predicting a poorer prognosis. A large
clinical trial is under way in Pittsburgh and Pisa to determine whether
manic/hypomanic symptoms in unipolar patients characterize a distinct
phenotype showing a differential response to treatment with SSRI,
interpersonal therapy, or a combination of the two."
David Kupfer, M.D., chair of psychiatry at the University of Pittsburgh and
one of the study authors, told Psychiatric News, "The
implications of this research for clinical psychiatrists are important since
many difficult-to-treat patients are difficult because they have a `dose' of
unipolar and bipolar features. While they are often diagnosed with non-bipolar
depression, there is a significant degree of subsyndromal lifetime bipolar
features that reduce the usual level of therapeutic responsiveness that can be
expected with SSRI or other interventions used to treat depression. This may
also be true in those individuals who do not respond to targeted psychotherapy
alone (interpersonal therapy or cognitive behavioral therapy). Many of these
individuals may require treatment sequencing or combination treatments to
achieve full recovery."
The study, "The Mood Spectrum in Unipolar and Bipolar
Disorder: Arguments for a Unitary Approach," is posted online at<http://ajp.psychiatryonline.org/cgi/content/full/161/7/1264>.▪
Am J Psychiatry20041611264