title: A pilot study of the effects of chronic paroxetine administration on hippocampal N-acetylaspartate in generalized anxiety disorder.
abstract: The neural basis of generalized anxiety disorder (GAD) is poorly characterized. The effect of chronic administration (12 weeks) of paroxetine, a selective serotonin reuptake inhibitor, on N-acetylaspartate (NAA), a marker of neuronal viability, was evaluated in adults with GAD using proton magnetic resonance spectroscopic imaging ((1)H MRSI) at 1.5 T. We hypothesized that, pretreatment abnormalities in hippocampal NAA/creatine (NAA/Cr) would normalize with symptomatic improvement. Nine GAD patients (mean age = 41.7 year; 4 females) received 12 weeks of open-label paroxetine treatment, flexibly dosed up to 60 mg/day. Clinical outcome was assessed with the Hamilton Anxiety Rating Scale (HAM-A). Multislice ( 1)H MRSI scans were performed at unmedicated baseline and following 6 and 12 weeks of treatment. Ten untreated healthy volunteers (HVs) (mean age = 37.1 year; 4 females) received scans at the same intervals. All patients achieved remission (HAM-A <or= 7) by week 12. Compared to HVs, GAD patients showed persistently lower levels of bilateral hippocampal NAA/Cr (17.7% mean decrease; Cohen's d = 1.29) that were maintained across all three time points, despite marked symptom improvement. This pilot study failed to support an association between a hippocampal neuronal marker and anxiolytic response to paroxetine, and suggests further investigation of potential trait-like hippocampal abnormalities in GAD.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. sanjay.mathew@mssm.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Mathew
authors.forename: R B
authors.initials: RB
authors.lastname: Price
authors.forename: D C
authors.initials: DC
authors.lastname: Shungu
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: E L P
authors.initials: EL
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Amiel
authors.forename: J D
authors.initials: JD
authors.lastname: Coplan
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001224:Aspartic Acid; D003401:Creatine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; C000179:N-acetylaspartate