Proton magnetic resonance spectroscopy in youth with severe mood dysregulation

Dickstein, Daniel P.; van der Veen, Jan Willem; Knopf, Lisa; Towbin, Kenneth E.; Pine, Daniel S.; Leibenluft, Ellen

doi:10.1016/j.pscychresns.2007.11.006

« Previous Next »Psychiatry Research: Neuroimaging
Volume 163, Issue 1 , Pages 30-39, 30 May 2008

Proton magnetic resonance spectroscopy in youth with severe mood dysregulation

Daniel P. Dickstein
- Unit on Bipolar Spectrum Disorders, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
- E.P. Bradley Hospital, East Providence, RI, USA
- Warren Alpert Medical School of Brown University, Providence, RI, USA
- Corresponding author. Bradley/Hasbro Children's Research Center, 1 Hoppin Street, Coro West Rm 2.056, Providence RI 02903, USA. Tel.: +1 401 793 8028; fax: +401 444 8742.
Jan Willem van der Veen
- Magnetic Resonance Spectroscopy Core, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
Lisa Knopf
- Unit on Bipolar Spectrum Disorders, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
- Emotion and Development Branch, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
Kenneth E. Towbin
- Unit on Bipolar Spectrum Disorders, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
- Emotion and Development Branch, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
Daniel S. Pine
- Emotion and Development Branch, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
Ellen Leibenluft
- Unit on Bipolar Spectrum Disorders, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA
- Emotion and Development Branch, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA

Received 22 March 2007; received in revised form 11 September 2007; accepted 19 November 2007.

Abstract

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus “hyperarousal” symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as “severe mood dysregulation” (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N=36) and controls (N=48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.