Principal Investigator: Ellen Leibenluft
Section on Bipolar Spectrum Disorders
Emotion and Development Branch
BiographyEllen Leibenluft, M.D. is Senior Investigator and Chief of the Section on Bipolar Spectrum Disorders and of the Emotion and Development Branch at the National Institute of Mental Health Intramural Research Program. Dr. Leibenluft received her B.A. from Yale University summa cum laude and her M.D. from Stanford University. After completing residency training at Georgetown University Hospital, she served on the faculty there as director of the psychiatric inpatient unit and day hospital. She came to the NIMH in 1989, and since that time has been conducting research on bipolar disorder.
As detailed below, Dr. Leibenluft’s research focuses primarily on the brain mechanisms involved in bipolar disorder and severe irritability in children and adolescents. Her work involves the use of cognitive neuroscience techniques and neuroimaging modalities, primarily functional MRI. She is also interested in novel treatment development for severe irritability, as well as the longitudinal course of both bipolar disorder and severe irritability in children. Dr. Leibenluft has won a number of honors, including the American Psychiatric Association Blanche F. Ittleson Award for Research in Child and Adolescent Psychiatry, the Litchfield Lecture at Oxford University, and the Michael Rutter Lecture of the Royal College of Psychiatrists. She serves on several Editorial Boards, including the American Journal of Psychiatry, Biological Psychiatry, and Bipolar Disorders, and is a Deputy Editor of the American Journal of Child and Adolescent Psychiatry.
Dr. Leibenluft’s group strives to have research participation be a positive experience for children and their families. In addition, she places a strong emphasis on mentoring trainees at all levels and on creating a collaborative and productive environment within the Section.
Dr. Leibenluft’s major research interests center on the brain mechanisms mediating bipolar disorder and severe irritability in children and adolescents. Dr. Leibenluft has a long-standing interest in bipolar disorder, and she extended her research focus to also include children with severe irritability because of questions in the field as to whether chronic, severe irritability should be considered to be a presentation of bipolar disorder in children. Her research indicates different adult outcomes of childhood irritability vs. bipolar disorder, and suggests differences between the two clinical presentations in family history and brain function. To facilitate research on children with severe, impairing irritability, Dr. Leibenluft’s group defined the syndrome of severe mood dysregulation (SMD; Leibenluft et al, 2003); this research informed the inclusion of Disruptive Mood Dysregulation Disorder (DMDD) in DSM 5.
The Section conducts clinical research on youth with bipolar disorder (BD), those at familial risk for BD and those with severe, impairing irritability. For each of our target populations, our goal is to elucidate the brain mechanisms mediating psychopathology in order to inform novel treatment approaches. To accomplish this, we employ an applied neuroscience approach, i.e., we first use standardized behavioral paradigms to assess responses to emotion stimuli and related psychological functions (e.g., cognitive control, attentional processes) and then, when between-group differences are found, we use functional MRI (fMRI) to study the mediating neural circuitry. The Section takes a developmental approach, in that our work in youth at risk for BD includes children preschool age through adolescence, and we perform studies comparing adults and children with BD. In addition to fMRI, we conduct structural MRI and DTI studies. Among the Section’s findings is the identification of emotion identification deficits and amygdala dysfunction during face emotion processing as potential endophenotypes for bipolar disorder in youth with, or at risk, for bipolar disorder.
Our work on children with severe irritability initially focused on clinical and brain-based comparisons between such youth and those with clearly episodic bipolar disorder. As noted above, these studies elucidated important differences between the two populations, and that line of research continues. In addition, our research on severely irritable youth has evolved to include a focus on the brain mechanisms mediating irritability per se. For example, we developed tolerable and ethically appropriate methods of inducing mild but discernible frustration during neuroimaging, so that the brain mechanisms of frustration and, by extension, irritability, can be studied in real time. Consistent with the NIMH’s Research Domain Criteria, or RDoC, initiative, which focuses research on dimensional traits seen across traditional diagnostic boundaries , we are now studying the brain mechanisms of irritability, not only in youth with SMD, but also in those with anxiety disorders or bipolar disorder. Finally, there is a significant need for research on the treatment of severe irritability, and we are currently conducting a controlled clinical trial of methylphenidate plus citalopram in the treatment of SMD.
Parametric modulation of neural activity by emotion in youth with bipolar disorder, youth with severe mood dysregulation, and healthy volunteers. Thomas LA, Brotman MA, Muhrer EJ, Rosen BH, Bones BL, Reynolds RC, Deveney CM, Pine DS, Leibenluft E. Arch Gen Psychiatry. 2012 Dec 1;69(12):1257-66. doi: 10.1001/archgenpsychiatry.2012.913. PMID: 23026912.
Differing amygdala responses to facial expressions in children and adults with bipolar disorder. Kim P, Thomas LA, Rosen BH, Moscicki AM, Brotman MA, Zarate CA Jr, Blair RJ, Pine DS, Leibenluft E. Am J Psychiatry. 2012 Jun;169(6):642-9. doi: 10.1176/appi.ajp.2012.11081245. PMID: 22535257.
Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Leibenluft E. Am J Psychiatry. 2011 Feb;168(2):129-42. doi: 10.1176/appi.ajp.2010.10050766. Epub 2010 Dec 1. PMID: 21123313.
Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. Rich BA, Schmajuk M, Perez-Edgar KE, Fox NA, Pine DS, Leibenluft E. Am J Psychiatry. 2007 Feb;164(2):309-17. PMID: 17267795.
Defining clinical phenotypes of juvenile mania. Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS. Am J Psychiatry. 2003 Mar;160(3):430-7. PMID: 12611821.
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