Date of Graduation

5-2025

Document Type

Thesis

Degree Name

Bachelor of Science in Biology

Degree Level

Undergraduate

Department

Biological Sciences

Advisor/Mentor

Leong, Josiah

Committee Member

Du, Yuchun

Second Committee Member

Forbes, Kristian

Third Committee Member

Hare, Laurence

Abstract

Adolescent depression has quickly grown in prevalence, yet the underlying neuropathology remains poorly understood. Anhedonia–the diminished ability to experience pleasure–is a core symptom of melancholic depression. Early identification of biomarkers associated with anhedonic depression could help mitigate the severity of the disorder by enhancing treatment efficacy. Blunted functionality of the nucleus accumbens (NAcc), the reward center of the brain, and abnormal dopaminergic activity in the ventral tegmental area (VTA) have both been linked to depression. Furthermore, glutamatergic input from the hypothalamus modulates the VTA which in turn, downregulates dopamine release in the NAcc. However, there is limited evidence supporting that the white matter tract connecting these three microstructures, the infero-medial medial forebrain bundle (imMFB), exhibits any abnormalities. The aim of this study was to characterize the imMFB in adolescents with anhedonic depression. Data from the Adolescent Brain Cognitive Development (ABCD) study was extracted to create a total sample size of 2,931 subjects, which was broken down into four subgroups: high depression and high anhedonia (hDhA), high depression and low anhedonia (hDlA), low depression and high anhedonia (lDhA), and low depression and low anhedonia (lDlA). Functional magnetic resonance imaging (fMRI) data from the Monetary Incentive Delay (MID) task was collected to examine NAcc activity during reward anticipation. Structural coherence of the imMFB was quantified by using fractional anisotropy (FA), a metric used in diffusion magnetic resonance imaging (dMRI). Subjects with high levels of anhedonia exhibited lower structural coherence in the last 25% of the left imMFB and higher structural coherence in the first 25% of the right imMFB. Subjects with high levels of depression exhibited blunted NAcc activity while anticipating small rewards; however, this decreased functionality was not correlated to FA values of the imMFB. Results indicated that structural abnormalities found in the imMFB may be more strongly associated with anhedonia, while functional blunting of the NAcc is linked to depression.

Keywords

Nucleus accumbens; medial forebrain bundle; depression; adolescent; ABCD study; diffusion MRI

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