Aim: The substantia nigra pars compacta (SNc), a vital part of the brain that produces dopamine, is being closely studied due to its potential role in the monoamine hypothesis, which aims to explain the causes of Major Depressive Disorder (MDD). Dopamine, a chemical messenger in the brain, is linked to the monoamine hypothesis, suggesting that imbalances in these chemicals may contribute to MDD. This study aimed to calculate volumetric changes in the substantia nigra (SN), using brain magnetic resonance imaging (MRI) in individuals diagnosed with MDD. Material and Method: Sixty-six participants, comprising 33 individuals diagnosed with MDD (mean age=44.30±13.98 years) and 33 healthy individuals (mean age=46.27±14.94 years), were recruited from the university hospital psychiatry outpatient clinic. In the MDD group, there were 15 male participants (45%) and 18 female participants (55%). The healthy control group consisted of 28 males (84.8%) and 5 females (16.2%). Potential confounding factors, such as underlying chronic diseases, were ruled out by the clinician through a thorough examination of the patient's medical history, ensuring the study outcomes were not influenced. Three-dimensional brain MRI scans were conducted using a 1.5 Tesla MRI scanner. Volumes of the SN and midbrain were automatically computed using MRIStudio, an atlas-based image analysis program. Results: Statistically significant higher volumes were observed in the right SN in the MDD group compared to controls (0.146±0.045 cm³ vs. 0.122±0.035 cm³, p=0.02, p
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