Laura Ladekarl, Class of 2025

Dopamine, central in the brain’s reward system, plays a key role in addiction and reward processing. Studies have shown that individuals with substance use disorders (SUDs) show reduced dopamine release and fewer receptors, even after prolonged periods of abstinence from their drug of choice. Neuromelanin-sensitivity magnetic resonance imaging (NM-MRI) visualizes and quantifies the concentration of Neuromelanin (NM) in brain tissues. It also examines the signal in neural structures near the dopamine-mediated complex SN-VTA, going from the substantia nigra (SN), to the ventral tegmental area (VTA). This allows researchers to identify dopamine-producing neurons and measure the NM concentration of these neurons. When applying an NM-MRI signal near the SN-VTA complex, it enables calculations of a contrast-to-noise ratio (CNR), an assessment of signal intensity differences between regions contrasted to background noise. More dopamine means higher CNR signaling intensity. While SUDs are widely researched in adults, there is not much regarding how the brains of adolescents with a history of substance use may display alterations in their ST-VTA circuits. Dr. Perlman and his colleagues from Stony Brook University hypothesized that cumulative substance use would be associated with a greater NM-MRI CNR. 

The study gathered data from 135 participants, 105 women and 30 men between the ages of 20 and 24, at Stony Brook University. The researchers used the K-SADS-PL survey, which had participants report use, frequency, and longevity of 11 substances (e.g., nicotine, alcohol, etc.) to evaluate substance usage. For each drug the participant had used, they gave a brief interview about their usage. All participants then completed the DSM-5 SUD module to evaluate the presence of SUD symptoms. Subsequently, they reported their reward sensitivity through self-evaluating measures. Afterwards, NM-MRI signals were used to determine if there was a relationship to substance use. 

The results indicated that the NM-MRI signals had low correspondence with self-reported reward sensitivity, suggesting that increased dopamine function may not directly correlate with the subjective reward experience. Cumulative substance use exhibited a positive relationship with NM-MRI CNR, however, the results were only in women. This supported the hypothesis for women only, but these findings may be attributed to the larger female sample size. 

The results of this study suggest that dopamine functioning in the brains of adolescent girls with substance use disorders is altered, which could have implications for translational and etiological models of SUDs. Future studies with more balanced gender ratios are needed to determine if similar results occur across all genders. This will allow scientists to better understand the toll excessive drug use can take on the developing brain and aid in developing more effective treatments. 

Figure 1 Man seeking therapy while seeming distraught

Works Cited:

Perlman G, Wengler K, Moeller SJ, Kotov R, Klein DN, Weinstein JJ, Horga G, Abi-Dargham A. Association of Neuromelanin-Sensitive MRI Signal With Lifetime Substance Use in Young Women. Am J Psychiatry. 2024 Nov 1;181(11):997-1005. doi: 10.1176/appi.ajp.20220819. Epub 2024 Oct 9. PMID: 39380373; PMCID: PMC11637462.
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