Objective Outcome and family history data differentiate children with severe mood dysregulation (SMD), a syndrome characterized by chronic irritability, from children with “classic,” episodic bipolar disorder (BD). Nevertheless, the presence of cognitive inflexibility in both SMD and BD highlights the need to delineate neurophysiological similarities and differences between the two patient groups. We used fMRI to examine neural correlates of cognitive flexibility deficits in SMD and BD vs. healthy volunteers (HV). Method During fMRI, subjects completed a response reversal task that assesses cognitive flexibility (N=22 SMD, 26 BD, 34 HV). We examined task effects in four regions of interest: caudate, cingulate gyrus, inferior frontal gyrus (IFG), and ventromedial prefrontal cortex. Results Diagnosis-by-accuracy interactions emerged in caudate and IFG. In these regions, we calculated the difference in activation between incorrect vs. correct trials. In caudate, this value was smaller in both SMD and BD than in HV. In IFG, however, this value was smaller in SMD than in both BD and HV. Post-hoc analyses indicate that comorbid ADHD in patients may influence the caudate findings. Exploratory whole-brain analysis confirmed the caudate and IFG findings. In addition, other regions differentiating SMD and BD were identified (e.g., superior parietal lobule/precuneus and inferior temporal gyrus). Conclusions In response to errors, similar perturbations occur in the caudate for SMD and BD youth relative to HV youth. IFG deficits, in contrast, manifest in SMD, but not BD, youth.

Objective-An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be significantly less likely to develop (hypo-)manic or mixed episodes over time than will youth with bipolar disorder (BD). Method-Patients with SMD (N = 84) and narrowly defined BD (N = 93) at baseline were followed up in 6-monthly intervals using the relevant K-SADS modules to ascertain (hypo-)manic or mixed episodes.Results-Only one of 84 SMD subjects (1/84 [1.2%]; 95% confidence interval CI = 0.0003 to 0.064) experienced a (hypo-)manic or mixed episode during the study (median follow-up = 28.7 months). The frequency of such episodes was more than 50 times higher in those with narrowly defined BD (58/93 [62.4%]; 95% CI 0.52 to 0.72).Conclusions-These data suggest that, over an approximately 2-year follow-up period, youth with SMD are unlikely to develop (hypo-)manic or mixed episodes. Keywords bipolar disorder; pediatric; severe mood dysregulation; irritability; ADHD In American psychiatric clinics and inpatient settings, dramatic increases in the rates of diagnosis of pediatric bipolar disorder (BD) have been documented over the past decade, 1,2 with a concomitant increase in prescription rates for antipsychotic medication. 3 This rapid increase in the diagnosis of pediatric BD has coincided with the contention that the clinical presentation of BD differs between children and adults. 4,5 The debate regarding the pediatric presentation of BD is complex. One important aspect of it has been the suggestion that marked irritability, even when it does not constitute an episodic change from baseline, is a manifestation of BD in youth. 4,6,7 To provide a framework for research on whether irritable children without distinct manic episodes have a developmental presentation of BD, we operationalized 8 a clinical syndrome, severe mood dysregulation (SMD), designed to capture chronically irritable children whose diagnostic status is in doubt. This paper uses a longitudinal sample to investigate the extent to which subjects with SMD develop episodes of (hypo-)mania, compared to youth with narrowly defined BD.The criteria for SMD require a persistent, nonepisodic clinical presentation of negatively valenced mood with frequent and impairing anger outbursts, combined with at least three of the "B" criteria of mania (pressured speech, agitation, insomnia, and flight of ideas/racing thoughts) and one (distractibility) that is also common to ADHD. 8 A community-based follow-up study suggests that SMD is common, with a lifetime prevalence of 3.3% in youth 9 to 19 years of age. 9 Furthermore, in that sample SMD predicted depressive disorder at 7-year follow-up in youths who were 9 to 19 years old at baseline. 9 Consistent with this finding, another community-based study of nonepisod...

Background There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in bipolar disorder (BD) have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time. Furthermore, the developmental trajectories of structural abnormalities in BD or SMD are unknown. This study provides such data in BD, SMD, and HV. Methods An optimized, modulated voxel-based morphometry (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD, 55 BD, and 68 HV). Additionally, 92 children (31 SMD, 34 BD, and 27 HV) were re-scanned after two years (mean interval 1.99 ± 0.94 years), to compare time-related changes among the three groups. Results Cross-sectionally, the groups differed in gray matter (GM) volume in pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical differences were driven mainly by increased GM volume in HV compared to BD and SMD. In globus pallidus, there was increased GM in BD compared to HV and SMD. Longitudinally, group-by-time interactions were evident in two clusters in the superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both clusters, the interactions were driven by an abnormal increase in volume in BD. Conclusions Cross-sectionally, both BD and SMD are associated with structural abnormalities in frontal cortex, insula, and basal ganglia. While some of these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre-SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal cortex and precuneus are present in, and unique to, BD. Because of the high proportion of co-occurring ADHD in the SMD subjects, we could not separate effects of ADHD from those of SMD, and future research including a non-irritable ADHD group must address this issue.

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