title: Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex.
abstract: BACKGROUND
  The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone.
  
  
  METHODS
  Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88+/-2.99 years; one female) were medicated with the atypical antipsychotic risperidone.
  
  
  RESULTS
  Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels.
  
  
  CONCLUSIONS
  The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study.
  
  
  CONCLUSIONS
  Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.
authors.affiliation: Brain Imaging Center, McLean Hospital, Belmont, MA 02478, USA. const@mclean.harvard.edu
authors.forename: Constance M
authors.initials: CM
authors.lastname: Moore
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Janet
authors.initials: J
authors.lastname: Wozniak
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.forename: Megan
authors.initials: M
authors.lastname: Aleardi
authors.forename: Megan
authors.initials: M
authors.lastname: Wardrop
authors.forename: Meghan
authors.initials: M
authors.lastname: Dougherty
authors.forename: Terri
authors.initials: T
authors.lastname: Harpold
authors.forename: Paul
authors.initials: P
authors.lastname: Hammerness
authors.forename: Edin
authors.initials: E
authors.lastname: Randall
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D002648:Child; D015897:Comorbidity; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D005973:Glutamine; D018698:Glutamic Acid; D018967:Risperidone; D003401:Creatine