Risks for the Transition From Major Depressive Disorder to Bipolar Disorder in the National Epidemiologic Survey on Alcohol and Related Conditions

Abstract

Objective It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder. Methods We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions. Results Approximately 1 in 20 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, Black race/ethnicity, and less than high school education. Clinical characteristics of depression (e.g., age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (Odds Ratio=2.20; 95% Confidence Interval=1.47, 3.30) and generalized anxiety disorder (OR=1.58; CI=1.06, 2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR=1.26; CI=1.12, 1.42) and past-year problems with one's social support group (OR=1.79; CI=1.19, 2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest. Conclusions A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD, and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder.

Excessive Mood Elevation and Behavioral Activation with Antidepressant Treatment of Juvenile Depressive and Anxiety Disorders: A Systematic Review

“…Although depression commonly precedes manifestations of mania or hypomania in patients diagnosed with BPD [3,79,82], anxiety disorders or anxious depression may also be antecedents of later BPD, as well as being common comorbidities with BPD [6,28,30,89,90,91,92,93,94,95]. As we found (table 1; online suppl.…”

“…Such activation responses have often been reported in association with AD treatment, and may be particularly likely among juvenile depressed patients who have not yet experienced a spontaneous episode of mania or hypomania, and are a clinically important basis of initially recognizing BPD in previously depressed patients [3,4,8,11,13,14,77,78]. The relatively high rates of excessive arousal-activation encountered seem inconsistent with typical exclusion of patients with known BPD from most AD trials [79], but are consistent with the view that BPD is not easily diagnosed in juveniles [59,60,80,81,82,83]. …”

“…Even though such responses do not necessarily prove the presence of previously undiagnosed BPD, it is important to note that continued use of ADs in cases of unrecognized BPD can lead to sustained mood instability [2,79,82,84]. This consideration underscores the potential significance of even moderately excessive arousal-activation in guiding to future clinical management to monitor for similar future responses and for possible BPD, while considering the use of mood-stabilizing treatments judiciously.…”

Can unipolar and bipolar pediatric major depression be differentiated from each other? A systematic review of cross-sectional studies examining differences in unipolar and bipolar depression

“…The early age of onset of depression has been extensively reported as a strong risk factor of manic switches in the literature examining the course of illness in adults. However, "early onset" in these works is classified as the emergence of symptoms in adolescence to early adulthood (younger than 25 years old) (Akiskal et al, 1983;Coryell et al, 1995;Angst et al, 2005;Beesdo et al, 2009;Zimmermann et al, 2009;Gilman et al, 2012;Dudek et al, 2013). It is noteworthy that similar results were found for children under the age of 18.…”

Dr Gilman and Colleagues Reply

“…We agree with Wakefield and his colleagues that social context is an important consideration in defining the pathological significance of depressive symptoms and that aspects of social context, including the loss of a loved one, are important determinants of the onset and clinical course of major depression. [11][12][13] We believe that psychiatry should strive to move beyond a purely descriptive nosology to one based on etiology. Unfortunately, our results suggest that the validity of the current distinction between uncomplicated and complicated bereavement remains unclear.…”