The pathophysiology of irritability may differ between pediatric patients with severe mood dysregulation and those with narrow-phenotype bipolar disorder, according to a report in the February American Journal of Psychiatry. Thus, different treatments may be required for children with the two disorders.

“The current study is the first to provide evidence of behavioral and psychophysiologic differences between possible phenotypes of pediatric bipolar disorder,” Brendan A. Rich, PhD, and colleagues stated. Twenty-one children with severe mood dysregulation, 35 children with narrow-phenotype bipolar disorder, and 26 control children were examined to compare behavioral and psychophysiological correlates of irritability. In accordance with the broad phenotype conceptualization of bipolar disorder, severe mood dysregulation was defined as “nonepisodic irritability accompanied by hyperarousal and hyperreactivity to negative emotional stimuli without elation or grandiosity” at least three times weekly, the researchers stated. As outlined by the DSM-IV, the narrow-phenotype bipolar disorder category required the presence of at least one episode of mania or hypomania with abnormally elevated mood.

All three groups of children (ages 7 to 17) completed the affective Posner task, which is designed to manipulate emotional demands and cause frustration. Twenty-eight of the 35 children (80%) with narrow-phenotype bipolar disorder met criteria for bipolar I disorder. Among children with severe mood dysregulation, eight (38%) had a history of major depressive disorder.

DOUBLE DISSOCIATION

Although patients in both the severe mood dysregulation and narrow-phenotype bipolar disorder groups reported significantly more arousal during frustration than controls, behavioral and psychophysiologic performance differed between the two groups. According to the researchers, children with narrow-phenotype bipolar disorder had significantly lower P3 amplitude than children with severe mood dysregulation or controls during frustration, but they showed no N1 amplitude deficit, which reflected executive attention impairments.

However, children with severe mood dysregulation displayed impairment in the initial stages of attention, as they had significantly lower N1 event-related potential amplitude than controls or children with narrow-phenotype bipolar disorder, regardless of the presence of frustration, but displayed no P3 amplitude. Additionally, the N1 deficit in children with severe mood dysregulation was associated with oppositional defiant disorder symptom severity, and while these children had significantly lower P1 amplitude than did controls, P1 amplitude did not differ significantly between children with narrow-phenotype bipolar disorder and controls.

“Attenuated N1/P1 amplitude, previously documented in ADHD, suggests that children with severe mood dysregulation have deficits in initial attention regardless of emotional context, possibly accounting for their low accuracy,” Dr. Rich and colleagues pointed out. “Whereas narrow-phenotype bipolar subjects displayed decreased P3 amplitude when frustrated, the children with severe mood dysregulation displayed normal P3 amplitude, suggesting that they can modulate their attention properly in the context of increased emotional demands.”

DISTINCTIONS BETWEEN CRITERIA

The authors pointed out that severe mood dysregulation, oppositional defiant disorder, and ADHD have closely related definitions that, to a certain extent, could be used to describe the same group of children. However, severe mood dysregulation has criteria for irritability and impairment secondary to irritability that are stricter than those of ADHD and oppositional defiant disorder with depression-like irritability. In addition, the researchers’ criteria for narrow-phenotype bipolar disorder patients excluded only children with irritability, making the criteria stricter than the DSM-IV criteria.

“Chronic irritable mood does not appear to be sufficient to justify a bipolar disorder diagnosis, but it still remains possible that an episodic irritable phenotype would biologically correlate with the narrow bipolar phenotype,” stated S. Nassir Ghaemi, MD, MPH, and Andrés Martin, MD, MPH, in an accompanying editorial. “It remains to be seen whether, as some suspect, some instances of oppositional defiant disorder or ADHD represent childhood harbingers of what ultimately evolves into recognizable bipolar disorder in adulthood.” Drs. Ghaemi and Martin advised clinicians to rely on diagnosis and proven treatments, rather than to consider “a simplistic and potentially risky symptom-ameliorating polypharmacy.”

—John Merriman

Suggested Reading
Ghaemi SN, Martin A. Defining the boundaries of childhood bipolar disorder. Am J Psychiatry. 2007;164:185-188.
Rich BA, Schmajuk M, Perez-Edgar KE, et al. Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. Am J Psychiatry. 2007;164:309-317.

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