Abstract: For decades, the clinical identity of Parkinson’s disease (PD) has been anchored to its motor symptoms, such as tremor, rigidity, and bradykinesia, which arise from the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. However, for many patients, the most debilitating aspects of the disease are psychological and emotional rather than physical. Depression, in particular, is one of the most common and impactful non-motor neuropsychiatric symptoms, affecting up to 50% of patients with PD, often emerging years before the first signs of motor impairment (Poplawska-Domaszewicz et al., 2024). The prodromal depression is not merely a reaction to a debilitating diagnosis; rather, increasing evidence suggests that it is an integral part of the underlying neurobiology of the disease. The pioneering work of Halliday et al. (1990) and, subsequently, the pathological staging model proposed by Braak et al. (2003) more than two decades ago provided the first anatomical clue, demonstrating that the accumulation of aggregated α-synuclein (α-syn) protein, the hallmark pathology of PD, begins in the lower brainstem and affects the serotonergic (5-HT) raphe nuclei long before reaching the substantia nigra pars compacta. Understanding the consequences of early disruption of the 5-HT system is essential for improving quality of life and developing therapies that treat the whole patient, not just their motor deficits.