Since the beginning of this project we have screened over 1000 subjects for this study. We have enrolled approximately 110 youth with bipolar disorder (BD), 129 subjects at risk for BD because they have a parent or sibling with the illness, 140 control subjects, and 53 adults with BD. This year, approximately 75 new subjects were enrolled. Previous work on this project identified deficits in face emotion identification in youth with BD, as well as deficits in response flexibility. Work this year extended these findings to youth at risk and to adults with the illness. We published two papers indicating that youth at risk for BD have the same deficits in face emotion labeling as do youth with the illness. Specifically, compared to controls, both youth with BD and those at risk for the illness require more emotional information before identifying a face emotion correctly, and make more mistakes. This deficit is present across a range of emotions. This year we also obtained data indicating that adults with BD have the same deficit in face emotion procesing as do youth with BD and youth at risk for BD. In addition, we published data indicating that youth at risk for BD, like those with the illness, have deficits in sustained attention, as indexed by high intrasubject variability in response time. These attentional deficits may account for the abnormalities in cognitive flexibility that we have identified previously in youth with BD. Thus we have identified two potential endophenotypes, deficits in face emotion labeling and deficits in sustained attention in patients with BD. Endophenotypes are markers along the gene to illness pathway, and their identification could aid in the search for risk-related genes in BD and eventually lead to the development of strategies for early detection and prevention of BD. This year we also continued our studies designed to ascertain the neural dysfunction mediating the deficits in face emotion labeling and cognitive flexibility that we have observed. Previous work has implicated prefrontal-amygdala dysfunction in deficits in face emotion labeling in youth with BD. Data accepted for publication this year identifies how amygdala dysfunction differs among youth with BD, those with severe irritability and hyperarousal symptoms (severe mood dysregulation or SMD, see MH002786-07), those with attention deficit hyperactivity disorder (ADHD), and controls. In addition, other data being prepared for publication uses a different scanning paradigm and also finds differences among BD, SMD, and controls in amygdala function while viewing emotional faces. These data suggest that brain-based measures can be used to differentiate clinical groups, and ultimately point toward a future time when diagnosis in psychiatry will use such measures in addition to clinical assessment. Finally, other imaging studies conducted this year suggest differences between adults and youth with BD in the neural circuitry engaged when viewing emotional faces, particularly in the ventrolateral prefrontal cortex. An important development this year was the expansion of our program to include preschool children at risk for BD, again by virtue of having a sibling or parent with the illness. In recent years there has been a number of reports of preschoolers being diagnosed with BD, despite the fact that they are not reported to have the distinct manic episodes classically considered to be a hallmark of the illness. We decided that it was important to study preschoolers at risk for BD with state-of-the-art assessment techniques, as well as with neuroscience-based techniques adapted for use in this age group. Our work with preschoolers uses observational techniques to determine whether they have unusual degrees of irritability, as well as specialized computer tasks to determine whether they have the deficits in sustained attention and face emotion labeling that we identified in school-age children at risk for BD. To this point, we have demonstrated the feasibilty of this project and active data collection is ongoing. Finally, this year we initiated a doubel-blind, placebo-controlled trial of riluzole in children with BD and severe comorbid anxiety. Anxiety is a common and often impairing symptom in youth with BD, and preliminary data suggests that riluzole, a glutamatergic agent, may be effective in the treatment of anxiety in both youth and adults. To be eligible for this trial, children must have failed at least two courses of standard treatment. Withdrawal from their current medication regimen occurs on an inpatient unit at the NIH Clinical Center. Once treatment with riluzole or placebo has begun, patients can continue the trial in the day treatment center (if they live locally) or at home, depending on their clinical status. Recruitment has just begun and data collection is ongoing.
| Haller, Simone P; Kircanski, Katharina; Stoddard, Joel et al. (2018) Reliability of neural activation and connectivity during implicit face emotion processing in youth. Dev Cogn Neurosci 31:67-73 |
| Kircanski, Katharina; Clayton, Michal E; Leibenluft, Ellen et al. (2018) Psychosocial Treatment of Irritability in Youth. Curr Treat Options Psychiatry 5:129-140 |
| Vidal-Ribas, Pablo; Brotman, Melissa A; Salum, Giovanni A et al. (2018) Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder. Depress Anxiety 35:1207-1217 |
| Brotman, Melissa A; Kircanski, Katharina; Leibenluft, Ellen (2017) Irritability in Children and Adolescents. Annu Rev Clin Psychol 13:317-341 |
| Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E et al. (2017) Neural Markers in Pediatric Bipolar Disorder and Familial Risk for Bipolar Disorder. J Am Acad Child Adolesc Psychiatry 56:67-78 |
| Brotman, Melissa A; Kircanski, Katharina; Stringaris, Argyris et al. (2017) Irritability in Youths: A Translational Model. Am J Psychiatry 174:520-532 |
| Kircanski, Katharina; Zhang, Susan; Stringaris, Argyris et al. (2017) Empirically derived patterns of psychiatric symptoms in youth: A latent profile analysis. J Affect Disord 216:109-116 |
| Leibenluft, Ellen (2017) Pediatric Irritability: A Systems Neuroscience Approach. Trends Cogn Sci 21:277-289 |
| Pagliaccio, David; Wiggins, Jillian Lee; Adleman, Nancy E et al. (2017) Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder. Biol Psychiatry 82:669-678 |
| Hoffmann, Mauricio Scopel; Leibenluft, Ellen; Stringaris, Argyris et al. (2016) Positive Attributes Buffer the Negative Associations Between Low Intelligence and High Psychopathology With Educational Outcomes. J Am Acad Child Adolesc Psychiatry 55:47-53 |
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