Cerebrospinal fluid inflammatory cytokines and correlation with clinical features in early, untreated patients with Parkinson’s disease

The presence of depression and anxiety has been reported in several neurodegenerative conditions, not only in Parkinson’s disease (PD). However, the incidence seems higher in PD than in other chronic diseases and the onset of mood disturbances may even precede the motor symptoms. Non-motor symptoms (NMS) in PD are associated with a variety of poor outcomes. Research and clinical data suggest that the etiology of PD and of NMS is multifactorial. Even if the pathophysiological mechanisms behind NMS, mood disorders in particular, are poorly understood, recent advance in neuroinflammation have provide a better knowledge of these symptoms. The inflammatory hypothesis states that mood disturbances are caused by an activation of the inflammatory system, increasing production of cytokines that promote changes in neuroendocrine, neurochemical processes and in the metabolic pathway of serotonin. Neuroinflammation may be involved in the pathophysiology of PD and specifically in the initiation and/or maintenance of NMS in PD. Based on this hypothesis, immune and inflammatory biomarkers have been largely investigated in PD patients. The levels of inflammatory cytokines in peripheral blood tend to be higher in PD patients. Studies of brains from patients and animal models have provide several evidence for neuroinflammation involvement in PD. However, at present, the influence of inflammation on NMS in PD remains unclear. The present study aims to investigate the relationship between inflammatory cytokines in cerebrospinal fluid (CSF) and the severity of depression and anxiety in drug-naïve PD patients. The concentrations of cytokines (IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-13 and TNF-α) were assessed using a Bio-Plex multiplex assay (Bio-Rad Laboratories, Hercules, CA, USA) according to the manufacturer’s instructions. Beck Depression InventorySecond Edition (BDI-II) and State-Trait Anxiety Inventory (STAI) were used to assess the severity of depression and anxiety, respectively. A total of twenty-eight subjects were included in the study. After controlling for age, disease duration and motor impairment, BDI-II and STAI score were positively correlated with the CSF levels of IL-6, IL-8 and IL-10 in the CSF. We suggest that NMS in PD patients, such as depression and anxiety, might be generated via inflammatory mechanisms. These data are consistent with a growing body of literature that implicates inflammatory cytokines in neural and behavioral processes and further suggests that cytokines may be involved in NMS in PD. Our results suggest that, depression and anxiety in PD, 6 even in an initial phase of the disease, might be the result of complicated actions of neurotoxic and neuroprotective mediators.