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Predisposition to and effects of methamphetamine use on the adolescent brain

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Abstract

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

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Acknowledgements

This work was supported by NIDA Grants 1R01 DA024070 (to IK Lyoo and PF Renshaw), K05 DA031247 (to PF Renshaw), Grant KRF-2008-220-E00021 from the Global Research Network Program funded by the Korea Research Foundation (to IK Lyoo), the Global Top 5 program from the Ewha W University (to IK Lyoo) and Grant 2012R1A2A2A01010739 from the National Research Foundation of Korea (to IK Lyoo). We thank Y Cheon, SY Won, YS Kim and YS Kwon for assistance with data collection and recruitment and JS Kim, KM Kim and KI Yang for technical assistance.

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Correspondence to I K Lyoo.

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Professor IK Lyoo has received research support from Lundbeck, Eli Lilly, AstraZeneca, GSK, Nongshim and Pulmuone Holdings and Professor PFR has been a consultant for Ridge Diagnostics and Kyowa Hakko. The other authors declare no conflict of interest.

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Lyoo, I., Yoon, S., Kim, T. et al. Predisposition to and effects of methamphetamine use on the adolescent brain. Mol Psychiatry 20, 1516–1524 (2015). https://doi.org/10.1038/mp.2014.191

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