Research reportA diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: A 5-year retrospective study
Introduction
The under-diagnosis of bipolar disorder (BP) is common, and in fact, BP is often either not diagnosed at all or falsely diagnosed as major depressive disorder (MDD; (De Fruyt and Demyttenaere, 2007). The rate of misdiagnosis or under-diagnosis was approximately 80% in a community sample (Hirschfeld et al., 2003) and 40% in a hospitalized sample (Ghaemi et al., 1999). This may be partly due to the diagnostic criteria for BP because the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and DSM-5 criteria require the occurrence of a manic or hypomanic episode for a diagnosis of BP. It has been suggested that BP patients presenting with an episode of depression without a distinct history of mania/hypomania are practically impossible to diagnose correctly (Grotegerd et al., 2013), and approximately half of BP patients present with a major depressive episode as their first mood episode (Tondo et al., 2010, Etain et al., 2012). BP patients are three times more likely to suffer from depressive symptoms than from manic or hypomanic symptoms (Judd et al., 2002, Judd et al., 2003), and many BP-II patients seek help when in the depressed phase (Akiskal et al., 2000). Patients who begin BP with depressive episodes appear to be at increased risk for long-term morbidity, disability, and suicide (Baldessarini et al., 2010, Baldessarini et al., 2012).
The misdiagnosis and under-diagnosis of BP are due in part to the ‘soft’ symptoms of bipolarity that characterize patients with non-classical BP (Katzow et al., 2003). Consequently, the search for bipolar signatures in the symptoms and course of MDD has intensified. Several clinical markers of soft bipolarity have been suggested, including mixed anxiety/depressive symptoms (Katzow et al., 2003), conditions associated with impulsivity such as substance abuse, borderline personality, bulimia, and attention deficit disorder (Regier et al., 1990, Katzow et al., 2003), atypical depressive features (Perugi et al., 1998, Mitchell et al., 2001), early age of onset (Neuman et al., 1997, Benazzi, 2009), recurrent depressive episodes (Benazzi, 2009), a family history of BP in first-degree relatives (Benazzi, 2009), brief major depressive episodes (De Fruyt and Demyttenaere, 2007), antidepressant-induced mania/hypomania (Hirschfeld et al., 2003), post-partum depression (Judd et al., 2002), treatment resistance (Woo et al., 2008), and specific affective temperament types. i.e., depressive, cyclothymic, hyperthymic, irritable, and anxious (Rihmer et al., 2010).
The concept of ‘bipolar spectrum’ arose from the work of Dunner et al. (1970), whose definition of bipolarity included varying degrees of mania and hypomania. This concept was developed by Klerman (1981) and later by Akiskal (1996) to include the continuum from psychotic mania through other expressions of bipolar I disorder and bipolar II disorder, to soft subsyndromal manifestations of bipolarity, i.e., soft or subthreshold bipolarity (Nusslock and Frank, 2011).
Later, Ghaemi et al., 2001, Ghaemi et al., 2002 proposed an approach to the spectrum concept that focuses on how to distinguish BP from unipolar depression. He suggested that the following 11 features may predict the diagnosis of BP in patients with depressive symptoms and proposed that the definition of bipolar spectrum disorder (BPSD) is a potential sign of bipolarity: family history of BP in first-degree relatives; antidepressant-induced mania or hypomania; hyperthymic personality; recurrent major depressive episodes (>3); brief major depressive episodes (lasting an average of less than 3 months); atypical depressive symptoms; psychotic major depressive episodes; early age of onset of major depressive episodes (<25 years of age); postpartum depression; antidepressant “wear-off;” and treatment resistance (lack of response to ≥3 antidepressant treatment trials). Ghaemi et al. (2004) demonstrated that the proposed criteria can distinguish patients with bipolar depression from those with unipolar depression, but the proposed diagnostic criteria were not tested regarding their ability to predict the conversion from unipolar depression to BP.
A large proportion of patients suffering from MDD exhibit underlying soft bipolarity, and the identification of antecedents that predict the conversion from unipolar depression to BP would be highly beneficial for these patients. Thus, a set of patients diagnosed with MDD were retrospectively investigated in an attempt to identify the features and diagnostic criteria proposed for BPSD by Ghaemi et al. (2002) to analyze the predictive performance of the diagnostic criteria overall and of each clinical feature.
Section snippets
Patients and assessments
This study was a retrospective investigation that reviewed the medical records of patients who were hospitalized in the psychiatric ward of Yeouido St. Mary׳s Hospital, College of Medicine at The Catholic University of Korea in Seoul, Korea, between January 1, 2005 and December 31, 2008, with a diagnosis of MDD without prior history of mania or hypomania. The patients were clinically diagnosed with MDD according to the DSM-IV criteria at the index hospitalization. Those who were admitted for an
Results
During the study period, 448 patients were discharged with a diagnosis of MDD. Of these patients, 250 (55.8%) fulfilled the eligibility criteria for the study.
Discussion
To our knowledge, this is among the first studies to evaluate the predictive performance of the BPSD diagnostic criteria proposed by Ghaemi et al. (2001) regarding the diagnostic conversion of MDD to BP. As expected, the BPSD diagnostic criteria were highly predictive of the conversion from MDD to BP (OR=73.333), MDD to BP-I (OR=80.667), and MDD to BP-II (OR=66.000) during the 5-year follow-up period. The diagnostic conversion rates found in this study (BP-I: 2.0% per year; BP-II: 1.7% per
Role of funding source
Nothing declared.
Conflict of interest
No conflict declared.
Acknowledgments
The authors had no conflict of interest in conducting this study or preparing the manuscript.
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