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.

Brain connectivity aberrations in anabolic-androgenic steroid users

“…Despite the use of methods that are not necessarily directly comparable, our data-driven approach supports evidence from a small-scale study suggesting decreased functional connectivity between the amygdala and other brain regions in AAS users versus non-users (Kaufman et al, 2015). The findings are also in accordance with previous fMRI reports linking increases in testosterone levels to reductions in amygdala-prefrontal coupling (Peters et al, 2015, Spielberg et al, 2015, Volman et al, 2011), and reinforces the notion that testosterone fluctuations affect networks in the brain which are critically involved in emotional processing and regulation (Li et al, 2014, Phelps and LeDoux, 2005).…”

“…AAS has been associated with a wide array of adverse effects on mental health and also cognitive deficits (Heffernan et al, 2015b, Kanayama et al, 2012, Kaufman et al, 2015, Su et al, 1993). Perturbations of amygdala connectivity with cognitive and emotional network hubs including the DMN could potentially constitute brain correlates of these side effects.…”

“…In particular, due to the characteristic emotional consequences of AAS use, and converging neuroimaging evidence (Kaufman et al, 2015, Peters et al, 2015, van Wingen et al, 2011, Volman et al, 2011), we expected group differences in amygdala connectivity and in brain network nodes involved in cognitive and emotional regulation, which would also be sensitive to the severity of dependence and total exposure.…”

“…While positive effects of AAS on mood, such as transient euphoria and hypomania, have been reported early in the course of AAS use (Thiblin and Petersson, 2005), anxiety, impulsivity, marked irritability and aggression is commonly manifested after long-term use (Hall and Chapman, 2005, Pagonis et al, 2006b, Pope et al, 2000, Trenton and Currier, 2005). Moreover, emerging evidence suggests that prolonged AAS use is associated with cognitive impairments including self-reported memory (Heffernan et al, 2015a, Su et al, 1993), working memory and visuospatial abilities (Kanayama et al, 2012, Kaufman et al, 2015). …”

“…Using a seed-based approach targeting amygdala connectivity, it was found that resting-state coupling between the right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas, respectively, was significantly lower in 7 users compared to 9 non-users (Kaufman et al, 2015). Further, a recent meta-analysis of fMRI activation studies revealed significant amygdala foci both after testosterone administration and in endogenous testosterone studies (Heany et al, 2016), and higher endogenous testosterone levels have been linked to attenuated resting-state amygdala-prefrontal coupling in adolescents (Peters et al, 2015), and in healthy males during a social approach-avoidance task (Volman et al, 2011), and intranasal testosterone reduced amygdala coupling with the orbitofrontal cortex in females (van Wingen et al, 2011).…”