title: High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates.
abstract: OBJECTIVE
  It has been hypothesized that anomalies in monoaminergic function underlie some of the manifestations of bipolar disorder. In this study the authors examined the possibility that trait-related abnormalities in the concentration of monoaminergic synaptic terminals may be present in patients with asymptomatic bipolar disorder type I.
  
  
  METHODS
  The concentration of a stable presynaptic marker, the vesicular monoamine transporter protein (VMAT2), was quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior history of mania with psychosis (nine men and seven women) and individually matched healthy subjects were studied. Correlational analyses were conducted to examine the relationship between regional VMAT2 binding, cognitive function, and clinical variables.
  
  
  RESULTS
  VMAT2 binding in the thalamus and ventral brainstem of the bipolar patients was higher than that in the comparison subjects. VMAT2 concentrations in these regions correlated with performance on measures of frontal, executive function. In addition, sex differences in VMAT2 binding were detected in the thalamus of the bipolar patients; the male patients had higher binding than the women. No sex differences in binding were observed in the healthy comparison group.
  
  
  CONCLUSIONS
  These initial results suggest that higher than normal VMAT2 expression and, by extension, concentration of monoaminergic synaptic terminals, may represent a trait-related abnormality in patients with bipolar I disorder and that male and female patients show different patterns. Also, VMAT2 concentrations may be associated with some of the cognitive deficits encountered in euthymic bipolar disorder.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, 48104-1687, USA. zubieta@umich.edu
authors.forename: J K
authors.initials: JK
authors.lastname: Zubieta
authors.forename: P
authors.initials: P
authors.lastname: Huguelet
authors.forename: L E
authors.initials: LE
authors.lastname: Ohl
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: J M
authors.initials: JM
authors.lastname: Carr
authors.forename: B J
authors.initials: BJ
authors.lastname: Giordani
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
mesh_terms: D000328:Adult; D015415:Biomarkers; D001714:Bipolar Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D001933:Brain Stem / Q000737:chemistry; D003072:Cognition Disorders / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism; D012737:Sex Factors; D013747:Tetrabenazine / Q000031:analogs & derivatives*; D013788:Thalamus / Q000737:chemistry; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine