Irritability in Pediatric Bipolar Disorder

While there is widespread agreement that severe irritability is almost universal in children with mania, the role that irritability should play in the diagnosis of pediatric bipolar disorder remains controversial. According to Leibenluft and colleagues at the NIMH, trained observers appear to be able to differentiate normal from pathological irritability reliably, but the validity of the differentiation remains unknown. With our colleagues, we recently compared the clinical course of youth diagnosed with bipolar disorder on the basis of criterion A symptoms of episodic irritability versus elation. We found few differences, with the exception that irritable youth appeared to be at greater risk for depression. We also found that the relative severity of irritability and elation was unstable between episodes, contradicting the expectation that either irritability or elation symptoms would predominate over time for specific youth.

Future research on irritability and elation in pediatric bipolar disorder would be aided by more frequent and precise assessments of both irritability and elation during and between major mood episodes than we conducted. Recently, the Affective Reactivity Index (ARI), a concise parent- and self-report questionnaire designed by Stringaris and colleagues to assess youth irritability, performed well in differentiating normal adolescent subjects from those with severe mood dysregulation (SMD) and bipolar disorder. It was interesting and possibly unexpected that the SMD subjects had significantly higher average ARI scores than did bipolar subjects on the parent report (but no difference was found between the groups on self-report). Carlson and others have expressed concerns about whether the currently available research instruments can capture all of the clinically important dimensions of irritability with the precision needed for trials in which irritability is the primary outcome variable.

Persistence in the attempt to disaggregate distinct courses in pediatric bipolar disorder may reap rewards. Emerging data suggest that stratifying irritability into chronic versus episodic subtypes reveals differences in clinical course and family history as well as neurophysiologic markers. Such markers include performance in behavioral paradigms involving identification of facial emotions and induction of frustration. Expansion of these neurophysiologic studies, in combination with clinical trials, should result in improved recognition of and, ultimately, treatments for irritable moods in children and adolescents.

The NIMH has begun funding projects that employ Research Domain Criteria to develop new ways of classifying psychopathology based on observable behavior and neurobiological measures. The effort is to define basic dimensions of functioning (such as arousal and affect regulation) for study across multiple domains, from genes to neural circuits to behaviors, cutting across traditional DSM-defined disorders. Such efforts will hopefully lead to improved understanding of the heterogeneous illness course in pediatric bipolar disorder, enhance the identification and utility of emerging genetic and neuroimaging markers, and facilitate development of effective treatments.

Financial disclosure:Dr Hunt has received financial support from Wiley Publishers for The Brown University Child & Adolescent Psychopharmacology Update. Dr Case is a consultant for Blue Cross Blue Shield of Rhode Island and United Healthcare/Optum Health Behavioral Solutions.