Objective Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation. Method The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions. Results Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group’s responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups. Conclusions In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.

The results show that for nurses to be able to provide clinical leadership to their patients and colleagues, management must create empowering environments.

Background We used a dot-probe paradigm to examine attention bias toward threat (i.e., angry) and happy face stimuli in Severe Mood Dysregulation (SMD) vs. healthy comparison (HC) youth. The tendency to allocate attention to threat is well established in anxiety and other disorders of negative affect. SMD is characterized by the negative affect of irritability, and longitudinal studies suggest childhood irritability predicts adult anxiety and depression. Therefore, it is important to study pathophysiologic connections between irritability and anxiety disorders. Methods SMD patients (N=74) and HC youth (N=42) completed a visual probe paradigm to assess attention bias to emotional faces. Diagnostic interviews were conducted and measures of irritability and anxiety were obtained in patients. Results SMD youth differed from HC youth in having a bias toward threatening faces (p<0.01). Threat bias was positively correlated with the severity of the SMD syndrome and depressive symptoms; degree of threat bias did not differ between SMD youth with and without co-occurring anxiety disorders or depression. SMD and HC youth did not differ in bias toward or away from happy faces. Conclusions SMD youth demonstrate an attention bias toward threat, with greater threat bias associated with higher levels of SMD symptom severity. Our findings suggest that irritability may share a pathophysiological link with anxiety and depressive disorders. This finding suggests the value of exploring further whether attention bias modification treatments that are effective for anxiety are also helpful in the treatment of irritability.

Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations.

Background Pain is a major complication of sickle cell disease (SCD), spanning vaso‐occlusive crises and persistent pain. Although it is known that persistent pain is associated with considerable impairment in youth without SCD, little is known about the functional effects of persistent pain in SCD. The current study aimed to (a) characterize persistent pain in youth with SCD and (b) determine the extent to which youth with SCD and persistent pain differ in disease morbidity, functional impairment, and neurocognitive and psychological functioning. Procedure Eighty‐nine participants (ages 7‐16) and caregivers completed questionnaires (BRIEF [Behavior Rating Inventory of Executive Function], Conners‐3 [Conners—third edition], and PedsQL™‐SCD Module, where PedsQL is Pediatric Quality of Life Inventory). Participants completed neurocognitive tests WISC‐V [Wechsler Intelligence Scale for Children‐fifth edition], WJ‐III [Woodcock Johnson Tests of Achievement—third edition], and WIAT‐III [Wechsler Individual Achievement Test—third edition]). Youth were classified as having persistent pain if they reported daily pain for 7 days. Chi‐square and independent sample t‐test analyses were used to assess group differences (those with vs without persistent pain). Results Patients with persistent pain (n = 18) reported lower health‐related quality of life (P = .000). Caregivers were more likely to rate youth with persistent pain as having lower planning/organization abilities (P = .011) and clinically elevated symptoms of defiance/aggression and oppositional defiance (Ps = .00; .01). Patients with persistent pain demonstrated poorer working memory (P = .023) and processing speed (P = .027), and fewer demonstrating reading fluency abilities in the average or above range (P = .026). Conclusions Youth with SCD and persistent pain are at risk for psychosocial and neurocognitive impairments, suggesting that persistent pain may be an important indicator of disease burden. Furthermore, disease management may be enhanced by assessing cognitive and psychosocial functioning and incorporating interdisciplinary treatments addressing impairment associated with persistent pain.

Substantial evidence suggests that pharmacological manipulations of neural serotonin pathways influence ingestive behaviors. Despite the known role of the nucleus accumbens in directing appetitive and consummatory behavior, there has been little examination of the influences that serotonin receptors may play in modulating feeding within nucleus accumbens circuitry. In these experiments, the authors examined the effects of bilateral nucleus accumbens infusions of the 5-HT1/7 receptor agonist 5-CT (at 0.0, 0.5, 1.0, or 4.0 microg/0.5 microl/side), the 5-HT receptor agonist EMD 386088 (at 0.0, 1.0, and 4.0 microg/0.5 microl/side), or the 5-HT2C preferential agonist RO 60-0175 (at 0.0, 2.0, or 5.0 microg/0.5 microl/side) on food intake and locomotor activity in the rat. Intra-accumbens infusions of 5-CT caused a dose-dependent reduction of food intake and rearing behavior, both in food-restricted animals given 2-hr free access to Purina Protab RMH 3000 Chow, as well as in nondeprived rats offered 2-hr access to a highly palatable fat/sucrose diet. In contrast, stimulation of 5-HT receptors with EMD 386088 caused a dose-dependent increase of intake under both feeding conditions, without affecting measures of locomotion. Infusions of the moderately selective 5-HT2C receptor agonist RO 60-0175 had no effects on feeding or locomotor measures in food-restricted animals, but did reduce intake of the fat/sucrose in nonrestricted animals at the 2.0 microg, but not the 5.0 microg dose. Intra-accumbens infusions of selective antagonists for the 5-HT (SB 269970), 5-HT (SB 252585), and 5-HT2C (RS 102221) receptors did not affect locomotion, and demonstrated no lasting changes in feeding for any of the groups tested. These data are the first to suggest that the activation of different serotonin receptor subtypes within the feeding circuitry of the medial nucleus accumbens differentially influence consummatory behavior.

Objective Despite increased interest in the developmental trajectory of the pathophysiology mediating bipolar disorder (BD), few studies compare adults and youths with BD. Deficits in motor inhibition are thought to play an important role in the pathophysiology of BD across the age spectrum. Here we compare neural circuitry mediating this process in youths vs. adults with BD and healthy volunteers. Method fMRI data from 89 subjects (16 BD youth, 23 BD adults, 21 healthy children, 29 healthy adults) were acquired while subjects performed the stop-signal task. Results During failed inhibition, an age group x diagnosis interaction manifested in the anterior cingulate cortex (ACC), with child BD participants showing hypoactivation relative to healthy children and adult BD, and adult BD showing hyperactivation relative to healthy adults. During successful inhibition, a main effect of diagnosis emerged in the right nucleus accumbens and left ventral prefrontal cortex, with bipolar individuals, irrespective of age, showing less activation than healthy participants. Conclusions Child BD and adult BD both show ACC dysfunction during failed motor inhibition, although the nature of that dysfunction differs between groups. Adults and youth with BD show similar deficits in nucleus accumbens and ventral prefrontal cortex activation during successful inhibition. Therefore, while subcortical and VPFC hypoactivation is present in BD across the lifespan, ACC dysfunction varies developmentally, with reduced ACC activation in child BD and increased activation in adult BD during failed inhibition. Longitudinal fMRI studies on the developmental trajectory of the neural circuitry mediating motor inhibition in BD are warranted.

Background Youth with bipolar disorder (BD) show behavioral and neural deficits in cognitive flexibility; however, whether such deficits exist among youths at risk for BD has not been explored. Methods The current fMRI study examined the neural basis of cognitive flexibility in BD youth (n=28), unaffected youth at risk for BD (AR; n=13), and healthy volunteer youth (HV; n=21) by comparing brain activation patterns while participants performed the change task. On change trials, subjects must inhibit a prepotent response and execute an alternate one. Results During successful change trials, both BD and AR youth had increased right ventrolateral prefrontal and inferior parietal activity, compared to HV youth. During failed change trials, both BD and AR youth exhibited increased caudate activation relative to HV youth, but BD youth showed increased activation in the subgenual anterior cingulate cortex (ACC) relative to the other two groups. Conclusions Abnormal activity in ventrolateral prefrontal cortex, inferior parietal cortex, and striatum during a cognitive flexibility task may represent a potential BD endophenotype, but subgenual ACC dysfunction may represent a marker of BD illness itself.