The main goals of this longitudinal follow-up study were to determine whether the relative severity of the DSM-IV criterion A manic symptoms of irritability versus elation in bipolar disorder was stable and distinguished illness course over 4 years. Our results were contradictory. We found that the relative severity of irritability versus elation was unstable. Maximum criterion A symptom severity at baseline and follow-up was modestly correlated for irritability and uncorrelated for elation, baseline group assignment failed to predict the course of irritability or elation severity, and baseline and follow-up assignments did not agree more than would be expected by chance. Together these findings suggest that the relative severity of irritability and elation are unstable and should not differentiate underlying clinical differences in bipolar disorder or meaningfully predict illness course.
Nonetheless, baseline group assignment based on relative symptom severity during the most serious lifetime manic episode did predict some differences in symptom severity and risk of mood episodes. Subjects categorized as irritable-only at baseline were syndromal or subsyndromal for depression for a greater proportion of the follow-up period than subjects categorized as both irritable and elated. While all groups experienced mania or hypomania for a similar proportion of the follow-up period, elated-only youth at baseline were most likely to report the absence of irritability and elation at every follow-up assessment. The scores on the K-SADS-MRS reflect that the subjects were not necessarily within a manic episode at the scheduled follow-up assessments.
We found statistically significant group differences in the mean severity of some criterion B symptoms, but the magnitude of these differences was too small to be of clear clinical significance.
No comparable studies of bipolar youth have reported on longitudinal course of criterion A symptoms, but data from adult samples have suggested that irritability confers distinctive risks. Overt irritability and psychomotor agitation appear to be markers for specific negative outcomes in adults in a subsyndromal bipolar mixed state,22
such as greater risk for suicide attempts23–25
and longer duration of episodes at intake.23
We found no increase in rate of suicide attempts and no difference between the criterion A groups with regard to time to remission in the irritable-only group over the 4 years.
Irrespective of baseline group assignment, subjects in our sample were more commonly syndromal or subsyndromal for depression than for mania, a finding concordant with adult studies of bipolar disorder.22,26
A 12-year follow-up of bipolar I disorder found that threshold and subthreshold depressive symptoms were over 3 times more frequent than threshold manic symptoms.22
The same group found that, in bipolar II disorder, the symptomatic course is dominated by depressive rather than hypomanic or cycling/mixed episodes.26
An important study limitation is that the primary instrument used to longitudinally track weekly mania severity, the A-LIFE PSR, does not assess elation and irritability separately. The K-SADS-MRS, which we did use to specifically assess irritability and elation, was used only for the most severe week in the month prior to each 6-month follow-up evaluation, which may or may not have been during a mood episode. By contrast, the baseline criterion A group assignments were derived using the most severe lifetime manic episode. Therefore, our baseline measures of criterion A symptom severity may be more clinically relevant than our follow-up measures. This difference may have contributed to the apparent longitudinal instability in relative criterion A symptom severity that we observed and also may explain why the baseline measures might predict depression course more powerfully than subsequent criterion A symptoms. Our baseline assessments were subject to recall bias, as were our follow-up assessments, although the interval between follow-up assessments was 8 months on average. We did not have data on interrater and test-retest reliability of our criterion A group assignments, and the reliability assessment procedure for bipolar diagnosis did not measure information variance (ie, independent interviewers may have elicited different information from the same subject), which could be an unknown source of diagnostic unreliability. The reliability of our weekly mood assessment, the A-LIFE PSR, is “good”27
by conventional interpretation, but measurement error of the A-LIFE PSR could have contributed to underestimation of group differences in illness course. Because the study sample was recruited by methods including referral from clinical programs and because the majority of subjects in COBY had already received treatment, our findings may not generalize well to never-treated youth.
The main clinical implication of this study is that, compared to bipolar youth with prominent elation symptoms, youth carefully diagnosed with bipolar disorder on the basis of episodic irritability experience a similar clinical course but may be at greater risk of depression. Future research on irritability and elation in pediatric bipolar disorder would be aided by more precise assessment of covariation in irritability and elation during and between major mood episodes. Improved characterization of distinct illness courses may enhance the identification and utility of emerging genetic and neuroimaging markers and facilitate development of targeted treatments.