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Irritability in Children With Mood Disorders Has Varying Sources


BETHESDA, Md. -- In children with bipolar disorder or severe mood dysregulation, extreme irritability sparked by frustration triggers distinctly different brain activity patterns, suggesting different psychophysiological mechanisms.

BETHESDA, Md., Feb. 1 -- The extreme irritability in children with bipolar disorder appears to spring from different wells of frustration than the irritability in children with severe mood dysregulation, NIH researchers reported.

In a study comparing children with bipolar disorder or severe mood dysregulation with unaffected controls, extreme irritability sparked by a task designed to induce frustration revealed distinctly different brain activity patterns, according to Brendan A. Rich, Ph.D., and colleagues here and at the University of Maryland.

"Our results indicate that there may be different psychophysiological mechanisms and behavioral correlates associated with frustration between children with narrow-phenotype bipolar disorder and those with severe mood dysregulation," the investigators wrote in the February issue of the American Journal of Psychiatry.

The findings, if borne out by further research, could lead to better differentiation and treatment of mood disorders in children, said the study's authors.

"If future research indicates that bipolar disorder and severe mood dysregulation are two separate disorders, this could guide parents and physicians toward the right treatments," said Dr Rich. "A good example is that medication prescribed for symptoms seen in severe mood dysregulation, such as stimulant medication, might be inappropriate for a child with classically defined bipolar disorder."

To assess whether irritability could be a diagnostic indicator for pediatric mania in bipolar disorder, the investigators looked for behavioral and psychophysiological correlates of irritability among 21 children with severe mood dysregulation, 35 with narrow-phenotype bipolar disorder, and 26 unaffected controls.

Severe mood dysregulation was defined as non-episodic irritability and hyperarousal without episodes of euphoric mood, and narrow-phenotype bipolar disorder was defined as a history of at least one manic or hypomanic episode with euphoric mood.

The children were evaluated with electroencephalography with electrodes recording signals from temporal, frontal, central and parietal sites as they performed the Posner task.

The task involved three tests in which children were asked to press a button on a screen corresponding to the location of a target. After a baseline run, the participants were told they could win or lose 10 cents for each correct or wrong response. On the third test run, the results were rigged so that the children were told they would lose 10 cents on slightly more than half of their correct responses, thereby manipulating emotional demands and inducing frustration.

After each task the children were asked to rate their responses to that task, reward, and punishment using the Self-Assessment Manikin with line-drawings showing extremes of happy or unhappy (to assess valence), or calm or aroused (to assess arousal).

The authors measured the children's mood response, behavior (reaction time and accuracy), and brain activity (event-related potentials).

They found that both the children with severe mood dysregulation and narrow-phenotype bipolar disorder reported significantly more arousal than controls when they were frustrated, but that the arousal resulted in different behavioral and psychophysiological performance between the patient groups.

For example, when frustrated, children with bipolar disorder had lower signal amplitude in the parietal lobe (P3 lead) than either children with severe mood dysregulation or controls. This difference indicates that the children with bipolar disorder have impairments in executive attention, the authors wrote.

In contrast, children with severe mood dysregulation had lower N1 (auditory evoked) event-related potential amplitude than children with narrow-phenotype bipolar disorder or controls, regardless of the emotional context. This difference reflected impairments in the initial stages of attention in the children with severe mood dysregulation, the investigators stated.

In post hoc analyses, the investigators determined that in the children with severe mood dysregulation, the N1 deficits were associated with the severity of symptoms of oppositional defiant disorder.

"Whereas the deficits in the narrow-phenotype subjects indicated impaired allocation of attention in the context of frustration, those in the severe mood dysregulation group indicated impairments in the initial stages of attention across emotional and non-emotional tasks," the investigators wrote.

"Finally, whereas the deficits in the narrow-phenotype cohort are consistent with those seen in mood disorders, deficits in children with severe mood dysregulation may reflect concurrent oppositional defiant disorder. The current study is the first to provide evidence of behavioral and psychophysiological differences between possible phenotypes of pediatric bipolar disorder," they concluded.

The investigators acknowledged that the results were confounded by the fact that the majority of children in the study with bipolar disorder were on medication, whereas most of the children with severe mood dysregulation were not medicated. There have been no studies showing that medication decreases P3 amplitude, however, suggesting that medication could not have accounted for the differences they saw in children with bipolar disorder, they wrote.

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