title: Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a proton magnetic resonance spectroscopy study.
abstract: We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment remitters and nonremitters. Secondary aims of this study were to identify neurochemical predictors of successful olanzapine treatment and other neurochemical effects of olanzapine. In all, 20 adolescents admitted for their first hospitalization for bipolar disorder, type I, manic or mixed and 10 demographically matched healthy subjects were recruited. Manic adolescents were treated with olanzapine monotherapy and scanned at three time points (N = 19). Medial and left and right lateral ventral prefrontal NAA, choline, creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at baseline, prior to receiving medication, and on days 7 and 28 of treatment. Healthy subjects did not receive medication but underwent 1H MRS scans at the same time points to assess for normal variability in metabolites over time. Although there was no overall increase in NAA in manic adolescents following 28 days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a greater increase in medial ventral prefrontal NAA compared with nonremitters (N = 8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic adolescents treated with olanzapine had an increase from baseline to day 7 in medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline. Baseline medial ventral prefrontal choline was greater in olanzapine remitters than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine may lead to increased ventral prefrontal neuronal viability and/or function as compared to unsuccessful treatment with olanzapine. Additionally, olanzapine-induced increases in choline may lead to alteration of abnormalities in cell membrane metabolism or second messenger pathways that are thought to be involved in the pathophysiology of bipolar disorder.
authors.affiliation: Division of Bipolar Disorders Research, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0559, USA. delbelmp@email.uc.edu
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cecil
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Adler
authors.forename: John P
authors.initials: JP
authors.lastname: Daniels
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strakowski
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D000077152:Olanzapine; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D011522:Protons; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D011522:Protons; D001569:Benzodiazepines; D001224:Aspartic Acid; C000179:N-acetylaspartate; D000077152:Olanzapine