Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

• Anabolic-androgenic steroids (AAS) cause psychiatric and cognitive abnormalities.
• We conducted the first systematic brain imaging study of human long-term AAS users.
• AAS users had larger right amygdalas and reduced right amygdala fMRI connectivity.
• AAS users also had dorsal anterior cingulate cortex neurochemical abnormalities.
• AAS use causes brain changes that may underlie psychiatric and cognitive changes.

BackgroundAnabolic-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.MethodsThis 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).ResultsAAS 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).ConclusionsLong-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.