Inflammatory markers and depression in Parkinson's disease: a systematic review

Neurol Sci. 2022 Dec;43(12):6707-6717. doi: 10.1007/s10072-022-06363-7. Epub 2022 Aug 30.


Background: Parkinson's disease (PD) patients experience non-motor symptoms (NMS), which may appear before motor manifestations. The most common NMS is depression, affecting about 30-40% of PD patients. Both PD and depression are associated with an increased inflammatory burden, with studies showing elevation of diverse inflammatory markers in patients with both conditions.

Methods: A systematic review was conducted in PubMed and PsycINFO databases to investigate what inflammatory markers are associated with PD depression (PDD). Only studies in English that measured inflammatory markers and analyzed against depression scores in PD patients were included.

Results: A total of 1132 articles were retrieved, and 14 entries were found to be eligible. Twelve were cross-sectional studies, one was a cohort, and one was a non-randomized controlled trial. IL-17A was the only marker strongly associated with PDD, while studies assessing sIL-2R and serum amyloid A found a moderate correlation. C-reactive protein, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, and IL-6 yielded conflicting results. Their possible roles in PDD are discussed. PDD was also related to longer disease duration and other NMS, such as anxiety, fatigue, dementia, REM sleep behavior disorder, and autonomic dysfunction.

Conclusion: We suggest that these markers may be used for distinguishing isolated depression from that related to neurodegeneration, especially in individuals that concurrently present with other known prodromal symptoms of PD and other α-synucleinopathies. However, future prospective studies are warranted to confirm this hypothesis.

Keywords: Depression; Inflammation; Parkinson's disease; Systematic review.

Publication types

  • Controlled Clinical Trial
  • Systematic Review
  • Review

MeSH terms

  • Anxiety
  • Biomarkers
  • Depression / etiology
  • Humans
  • Parkinson Disease*
  • REM Sleep Behavior Disorder* / complications
  • Synucleinopathies*


  • Biomarkers