title: Neurochemical effects of quetiapine in patients with bipolar mania: a proton magnetic resonance spectroscopy study.
abstract: Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.
authors.affiliation: Division of Bipolar Disorder Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219-0516, USA. adlercb@ucmail.uc.edu
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Adler
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.forename: Wade A
authors.initials: WA
authors.lastname: Weber
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Jarvis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Welge
authors.forename: Wen-Jang
authors.initials: WJ
authors.lastname: Chu
authors.forename: Emily
authors.initials: E
authors.lastname: Rummelhoff
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jing-Huei
authors.initials: JH
authors.lastname: Lee
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strakowski
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016022:Case-Control Studies; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D000069348:Quetiapine Fumarate; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D001224:Aspartic Acid; C000179:N-acetylaspartate