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Published Online: 9 October 2024

Association of Neuromelanin-Sensitive MRI Signal With Lifetime Substance Use in Young Women

Greg Perlman, Ph.D. [email protected], Kenneth Wengler, Ph.D., Scott J. Moeller, Ph.D., Roman Kotov, Ph.D., Daniel N. Klein, Ph.D., Jodi J. Weinstein, M.D., Guillermo Horga, M.D., Ph.D., and Anissa Abi-Dargham, M.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Preprint
https://doi.org/10.1176/appi.ajp.20220819
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Abstract

Objective:

Midbrain dopamine function plays a key role in translational models of substance use disorders. Whether midbrain dopamine function is associated with substance use frequency and severity or reward function in 20–24 year-olds remains a critical gap in knowledge. The authors collected neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a validated index of lifetime dopamine function in the substantia nigra/ventral tegmentum area (SN-VTA) complex, to characterize altered dopamine function.

Method:

Midbrain NM-MRI contrast-to-noise ratio (CNR) was acquired in 135 20–24 year-olds (105 women and 30 men). A composite measure of cumulative substance use was derived from factor analysis of lifetime alcohol intoxications, lifetime cannabis use, use of nicotine in heaviest month, number of classes of drugs used, and ever meeting DSM-5 criteria for a SUD. Trait reward function was assessed by self-report.

Results:

Cumulative substance use was significantly positively associated with NM-MRI CNR in a large area of the bilateral SN-VTA complex, an effect which was driven by women (who comprised most of the sample) and by voxels with greater NM-MRI CNR, including the ventral tegmentum area. NM-MRI CNR was not associated with individual differences in trait reward function.

Conclusions:

History of substance use is associated with greater NM signal in NM-rich areas of the midbrain, especially in women. Future longitudinal studies with repeated NM-MRI assessments, especially in younger cohorts and while including more men, are warranted to evaluate whether aberrant dopamine function predates, follows, or is modulated by substance use.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Preprint
PubMed: 39380373

History

Received: 29 September 2022
Revision received: 5 January 2024
Revision received: 4 March 2024
Accepted: 26 March 2024
Published online: 9 October 2024

Keywords

  1. Substance-Related and Addictive Disorders
  2. Brain Imaging Techniques

Authors

Details

Greg Perlman, Ph.D. [email protected]
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Kenneth Wengler, Ph.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Scott J. Moeller, Ph.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Roman Kotov, Ph.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Daniel N. Klein, Ph.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Jodi J. Weinstein, M.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Guillermo Horga, M.D., Ph.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Anissa Abi-Dargham, M.D.
Renaissance School of Medicine (Perlman, Moeller, Kotov, Weinstein, Abi-Dargham) and Department of Psychology (Klein), Stony Brook University, Stony Brook, New York; Department of Psychiatry, Columbia University, New York (Wengler, Weinstein, Horga); and Division of Translational Imaging, New York State Psychiatric Institute, New York (Wengler, Horga).
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Notes

Send correspondence to Dr. Perlman ([email protected]).

Competing Interests

Dr. Abi-Dargham reports that she serves on the Scientific Advisory Board for Neurocrine, Sunovion, and Abbvie; on the Data Safety Monitoring Board for Merck; and as the Deputy Editor of Biological Psychiatry; holds stock options in Herophilus and Terran Life Sciences; and has received consulting fees/honoraria from Boehringer Ingelheim, Merck, Neurocrine, Otsuka, Roche, and Sunovion. Dr Horga reports an investigator-initiated sponsored research agreement from Terran Biosciences outside the submitted work and having filed patents for the analysis and use of neuromelanin-sensitive magnetic resonance imaging in central nervous system disorders licensed to Terran Biosciences with no royalties received (WO2021034770A1, WO2022192728A3, AU2021377338A1, AU2019359377A1). Dr Wengler reports having filed patents for the analysis and use of neuromelanin-sensitive magnetic resonance imaging in central nervous system disorders licensed to Terran Biosciences with no royalties received (WO2021034770A1, WO2022192728A3, AU2021377338A1). The remaining authors report no financial relationships with commercial interests.

Funding Information

This research was supported by National Institutes of Health grants to Dr. Perlman (R21DA049041), Dr. Moeller (R01DA051420, R01DA049733, R21DA051179, R21DA048196, and R61DA056423), Dr. Kotov (R01DA051420 and R01DA049733), and Dr. Weinstein (K23MH115291).

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