title: Brain and cognition abnormalities in long-term anabolic-androgenic steroid users.
abstract: BACKGROUND
  Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans.
  
  
  METHODS
  This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS).
  
  
  RESULTS
  AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053).
  
  
  CONCLUSIONS
  Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction.
authors.affiliation: McLean Imaging Center, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA. Electronic address: kaufman@mclean.harvard.edu.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Kaufman
authors.affiliation: McLean Imaging Center, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Janes
authors.affiliation: Biological Psychiatry Laboratory, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Hudson
authors.affiliation: Biological Psychiatry Laboratory, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brennan
authors.affiliation: Biological Psychiatry Laboratory, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Gen
authors.initials: G
authors.lastname: Kanayama
authors.affiliation: McLean Imaging Center, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kerrigan
authors.affiliation: McLean Imaging Center, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
authors.affiliation: Biological Psychiatry Laboratory, McLean Hospital, The Department of Psychiatry, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Harrison G
authors.initials: HG
authors.lastname: Pope
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D045930:Anabolic Agents / Q000009:adverse effects*; D000728:Androgens / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D059906:Neuroimaging; D009483:Neuropsychological Tests; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D005973:Glutamine; C009217:scyllitol; D018698:Glutamic Acid; D007294:Inositol
keywords: Amygdala; Anabolic-androgenic steroids; Glutamate; Magnetic resonance imaging; Magnetic resonance spectroscopy; Scyllo-inositol