Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths

Abstract

In recent years, increasing numbers of children have been diagnosed with bipolar disorder. In some cases, children with unstable mood clearly meet current diagnostic criteria for bipolar disorder, and in others, the diagnosis is unclear. Severe mood dysregulation is a syndrome defined to capture the symptomatology of children whose diagnostic status with respect to bipolar disorder is uncertain, that is, those who have severe, nonepisodic irritability and the hyperarousal symptoms characteristic of mania but who lack the well-demarcated periods of elevated or irritable mood characteristic of bipolar disorder. Levels of impairment are comparable between youths with bipolar disorder and those with severe mood dysregulation. An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood. Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups. No specific treatment for severe mood dysregulation currently exists, but verification of its identity as a syndrome distinct from bipolar disorder by further research should include treatment trials.

Figure 1

Research Diagnostic Criteria for Severe Mood Dysregulationa ^a Adapted from Leibenluft et al. (14).

Figure 2

Psychological Processes and Neural Circuits Hypothesized to Contribute to Pathologic Irritabilitya ^aACC=anterior cingulate cortex; PFC=prefrontal cortex; NAcc=nucleus accumbens.

Figure 3

Face Emotion Labeling Errors, Adjusted for Sex, Age, IQ, and Ethnicity, in Youths With Mood and Behavior Disordersa ^a Adapted from Guyer et al. (56). Bipolar disorder (N=42); severe mood dysregulation (N=39); ANX/MDD=generalized anxiety, social phobia, separation anxiety, and/or major depression (N=44); ADHD/CD=attention deficit hyperactivity disorder and/or conduct disorder (N=35); HC=healthy comparison subjects (N=92). Between-group differences: severe mood dysregulation > ANX/ MDD, ADHD/CD, p<0.01; bipolar disorder > ANX/MDD, ADHD/CD, p<0.001; severe mood dysregulation and bipolar disorder did not differ.

Figure 4

Left Amygdala Activation During Ratings of Subjective Fear Versus Nose Width While Viewing Neutral Facesa ^a Reprinted from Brotman et al. (58). ^b Amygdala activation in ADHD patients was greater than that for healthy comparison subjects (p=0.05). ^c Amygdala activation in ADHD patients was greater than that for bipolar disorder patients (p=0.05). ^d Amygdala activation in severe mood dysregulation patients was less than that for bipolar disorder patients (p=0.04). ^e Amygdala activation in severe mood dysregulation patients was less than that for ADHD patients (p<0.01). ^f Amygdala activation in severe mood dysregulation patients was less than that for healthy comparison subjects (p=0.04).