Molecular Mechanisms and Potential Biomarkers of Neuropsychiatric Disorders in Parkinson's Disease

Parkinson's disease (PD) is the second most common degenerative disease of the central nervous system, characterized by both motor and non-motor disorders. Non-motor disorders include dementia, depression, and anxiety. The prevalence of dementia increases with disease progression, affecting 24-31% of PD patients and up to 75% after 10 years. Furthermore, approximately 50% of PD patients suffer from depression, while anxiety affects around 31% of this population. Molecular factors, including genetic factors, are currently implicated in the manifestation of neuropsychiatric disorders. It is believed that dementia and affective disorders in PD may result from both disturbed homeostasis of proteins such as α-synuclein, amyloid beta, and phosphorylated tau, as well as increased inflammatory processes and impaired neurotransmission. Chronic microglial activation, elevated levels of proinflammatory cytokines, and oxidative stress contribute to the severity of neuroinflammation, which in turn contributes to neuronal dysfunction and synaptic abnormalities. While the effect of pathological proteins in PD primarily involves impairment of dopaminergic neurotransmission, disturbances in the serotonergic, noradrenergic, cholinergic, and glutamatergic systems are also observed. Furthermore, genetic risk factors have been identified in PD patients, including monogenic causes, which are rare in unselected populations. Identifying causative molecular targets in PD is essential for developing therapies for this neurodegenerative disease. In this review, we present current views on the involvement of molecular factors in the development of psychiatric disorders in patients with PD, suggesting that they may have diagnostic and predictive value in the future.