title: Neurometabolite effects of response to quetiapine and placebo in adolescents with bipolar depression.
abstract: OBJECTIVE
  Mood stabilizers have been reported to affect brain concentrations of myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and potential predictors of response to QUET in adolescents with bipolar depression.
  
  
  METHODS
  Twenty-six adolescents with bipolar depression participated in an 8-week placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and 4T at two sites, with 8 cm(3) voxels placed in the right and left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used to calculate absolute concentrations of NAA and mI.
  
  
  RESULTS
  Twenty-six subjects had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS] score). Although baseline ACC mI did not predict responder status, responders had significantly lower posttreatment ACC mI values than did nonresponders (3.27±.71 vs. 4.23±.70; p=0.004). There were no significant differences in the changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group (ACC: -0.55±1.3 vs.+0.25±1.5, p=0.23; right-DLPFC: -0.55±1.3 vs. 0.33±0.89, p=0.13; left-DLPFC: -0.04±0.91 vs.+0.29±0.61, p=0.41).
  
  
  CONCLUSIONS
  We found that posttreatment, not baseline, ACC mI levels were associated with response to QUET in adolescents with bipolar depression. There were no differences in NAA concentration changes between the QUET and PBO groups. Larger studies including different brain regions would help to clarify the effects of QUET on neurochemistry in patients with bipolar disorder.
authors: Pediatric Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5540, USA. kchang88@stanford.edu
authors: Kiki
authors: K
authors: Chang
authors: Melissa
authors: M
authors: Delbello
authors: Wen-Jang
authors: WJ
authors: Chu
authors: Amy
authors: A
authors: Garrett
authors: Ryan
authors: R
authors: Kelley
authors: Neil
authors: N
authors: Mills
authors: Meghan
authors: M
authors: Howe
authors: Holly
authors: H
authors: Bryan
authors: Cal
authors: C
authors: Adler
authors: Jim
authors: J
authors: Eliassen
authors: Daniel
authors: D
authors: Spielman
authors: Stephen M
authors: SM
authors: Strakowski
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D003987:Dibenzothiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate