title: Proton magnetic resonance spectroscopy in youth with severe mood dysregulation.
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.
authors.affiliation: Unit on Bipolar Spectrum Disorders, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA. Daniel_Dickstein@Brown.edu
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Dickstein
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van der Veen
authors.forename: Lisa
authors.initials: L
authors.lastname: Knopf
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Towbin
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use; D001143:Arousal / Q000502:physiology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D002908:Chronic Disease; D003401:Creatine / Q000378:metabolism; D003937:Diagnosis, Differential; D004292:Dominance, Cerebral / Q000502:physiology; D004311:Double-Blind Method; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D007508:Irritable Mood / Q000502:physiology*; D018020:Lithium Compounds / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D019964:Mood Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D010725:Phosphocreatine; D005973:Glutamine; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine