A prospective longitudinal study shows putamen volume is associated with moderate amphetamine use and resultant cognitive impairments.

Keith M Kendrick,Qiang Luo,Euphrosyne Gouzoulis-Mayfrank,Marc Tittgemeyer,Benjamin Becker,Joerg Daumann,Daniel Wagner,Philip Koester

doi:10.1093/psyrad/kkab001

Abstract

Amphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects. To prospectively determine effects of occasional ATS use on cognitive functioning and brain structure. In a prospective longitudinal study design, cognitive functioning and brain structure were assessed at baseline and at 12-month follow-up in occasional ATS users (cumulative lifetime use<10 units at baseline). Examination of change scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample, interim ATS use, memory decline, and putamen volume reductions were strongly associated. The present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology that might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

Highlights

Increasing rates of recreational amphetamine-type stimulant (ATS) use, predominately illicitly produced amphetamine (AMPH) and 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and of Amphetamine-type stimulants (ATS) users seeking treatment indicate that ATSs have become a major health problem (UNODC, 2011; 2014)
During the last decades converging evidence from different animal models indicates a neurotoxic potential of ATSs (Aguilar et al, 2020; Parrott, 2013; Moratalla et al, 2017).These animal studies have shown that the experimental application of varying dosage regimens of MDMA and amphetamines lead to long-term neurotoxic effects in rodent and nonhuman primate models, as indicated by a range of brain morphological and neurochemical indices
Accumulating evidence from human studies suggests that the chronic use of ATS is associated with altered brain morphology, deficient grey matter (GM) integrity in limbic-striato-prefrontal brain networks, as well as subtle yet consistently observed, deficits in cognitive and emotional functions that have been associated with this circuitry (Gouzoulis-Mayfrank et al, 2009; Wagner et al, 2013; Ersche et al, 2013; Mackey & Paulus, 2013; Parrott 2015)

Summary

Introduction

Increasing rates of recreational amphetamine-type stimulant (ATS) use, predominately illicitly produced amphetamine (AMPH) and 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and of ATS users seeking treatment indicate that ATSs have become a major health problem (UNODC, 2011; 2014). Convergent evidence from animal models and meta-analyses covering neuroimaging studies in human drug users suggest that prolonged drug use is associated with structural and functional adaptations in limbic-striato-prefrontal circuits of the brain (Everitt and Robbins, 2016; KlugahBrown et al, 2020; Ersche et al, 2013). Accumulating evidence from human studies suggests that the chronic use of ATS is associated with altered brain morphology, deficient grey matter (GM) integrity in limbic-striato-prefrontal brain networks, as well as subtle yet consistently observed, deficits in cognitive and emotional functions that have been associated with this circuitry (Gouzoulis-Mayfrank et al, 2009; Wagner et al, 2013; Ersche et al, 2013; Mackey & Paulus, 2013; Parrott 2015). Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. In the entire sample interim ATS use, memory decline and putamen volume reductions were strongly associated

Methods

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Conclusion