Examining the Role of the NAc-PFC Pathway in the Link Between  Examining the Role of the NAc-PFC Pathway in the Link Between  Adolescent Nicotine Exposure and Adulthood Depression

Harrison, Robin

Examining the Role of the NAc-PFC Pathway in the Link Between Examining the Role of the NAc-PFC Pathway in the Link Between Adolescent Nicotine Exposure and Adulthood Depression

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harrison_robin_msc_2026_thesis.pdf (1.52 MB)

Date

2026-02-19

Authors

Harrison, Robin

Abstract

There is a frequent association between nicotine exposure in adolescence and adulthood depression, but this relationship is poorly understood from a biological perspective. The nucleus accumbens and prefrontal cortex often display dysfunction during reward-based neuroimaging studies in nicotine users and depressed individuals. To explore these regions’ roles in this relationship, this project investigated activation of these areas during monetary reward through functional magnetic resonance imaging in individuals with (n=25) and without (n=25) adolescent nicotine exposure who may also have had a lifetime diagnosis of depression. This analysis found that individuals with a history of adolescent nicotine use displayed heightened activation to monetary reward in the prefrontal cortex compared to those without, and this phenotype was also present in nicotine-exposed individuals with a history of depression. These findings contribute to our understanding of nicotine’s influence on the adolescent brain, and may help elucidate the common association between nicotine use and depression.

Summary for Lay Audience

Although cigarette use has declined in recent years, adolescent nicotine exposure is currently rising due to the increased use of vaping products by this cohort. This trend is particularly concerning as there is a well-established association between nicotine use and neuropsychiatric disorders, including major depressive disorder. It is therefore important to better understand nicotine's long-term impact on the adolescent brain and disentangle the root of this relationship from a biological perspective. The nucleus accumbens and prefrontal cortex are involved in processing natural and drug-related rewards and losses, and frequently show lower activation to reward outcomes in both smokers and depressed individuals compared to healthy controls during neuroimaging studies. However, these regions have not been extensively studied in individuals with a history of both nicotine use and depression. To address this research gap, functional magnetic resonance imaging data was collected and analyzed from 50 individuals with and without adolescent nicotine exposure, who may also have had a lifetime diagnosis of depression. Participants completed a card-guessing game in the scanner that they believed would influence how much money they won from our study. This research found that individuals with both nicotine exposure and depression displayed heightened response in the prefrontal cortex during monetary reward outcomes compared to other subgroups. These findings contribute to our understanding of nicotine’s influence on the adolescent brain, and may help elucidate the common association between nicotine use and depression. Continuing to study this relationship from a biological perspective in the future could furthermore aid in developing interventions for prevention and treatment of both conditions.

Keywords

Nicotine, depression, functional magnetic resonance imaging, reward, nucleus accumbens, prefrontal cortex, vaping, adolescence, mesocorticolimbic pathway, translational research

URI

https://hdl.handle.net/20.500.14721/39516

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