. 2024 Sep 7;17:6113–6141. doi: 10.2147/JIR.S385825

Table 2.

Studies Measuring Peripheral IL-6 or TNF-α in Association with Depression or Anxiety in Parkinson’s Disease. Number of Asterisks Denote Significance Level (* P<0.05, ** P<0.01, *** P<0.001)

Assay source	Authors	Participants	Sudy design	Scale	Inflammatory marker	Results
Serum	Fu et al 2023¹⁵⁸	PD = 273, HC = 91	Cross sectional case control	HAMD-24, HAM-A, NMSS	TNF-α, IL-6, IL-8	IL-6 positively correlated with HAMD* and NMSS* in PD patients. IL-8 and TNF-α showed no significant correlations
Serum	Rastegar et al 2019¹⁴⁹	PD = 160 (80 with LRRK mutation)	Longitudinal cohort study	GDS	MIP1β, IL-6, IFNY, IL-1RA, IL-5, GM-CSF, TNFα, CCL5, IL-2, IL-1β, CCL11, bFGF, VEGF, PDGF, CXCL10, IL-13, IL-4, MCP-1, IL-8, MIP1α, IL-10, GCSF, IL-15, IL-7, IL-12(p70), IL-17A, and IL-9	The following baseline inflammatory markers correlated with fold change in GDS over 2 years in all patients: IL5 = 0.609, IL8 = 0.415, GCSF = 0.438*, MIP1β = 0.294, IL10 = 0.435*, MIP1β = 0.294, IL6 = 0.320, IL1RA = 0.546, TNFα = 0.436, CCL5 = 0.337, bFGF = 0.301, VEGF = 0.640, MIP1α = 0.435, IL7 = 0.350, IL15 = 0.643**. There were no other significant correlations with other markers.
Serum	Veselý et al 2018⁸⁷	PD = 47	Longitudinal cohort study	MADRS	CRP, C3, C4, IL-6	Increased baseline levels of IL-6 associated with higher MADRS scores at follow up (2 years), rho = 0.366*
Plasma	Selikhova et al 2002¹⁶²	PD = 45 (27 with depression, 18 without depression), HC = 15	Longitudinal cohort study	BDI, STAI	IL-6	Higher IL-6 in PD with depression compared to PD. Increases in IL-6 correlated with BDI scores r=0.64* and anxiety scores r=0.65*** in PD group.
Blood (Unspecified)	Wan et al 2023¹⁶⁴	PD = 51 (with depression) HC = 51	Cross sectional case control	HAM-A, HAMD	IL-6, S100β, mi-RNA-218-5p and mi-RNA-320a-5p	Negative correlation between miR-218-5p and HAM-A r = −0.4163, HAMD r = −0.4927. No other significant findings between inflamamtory markers and depression scores.
Blood (Unspecified)	Wang et al 2016¹⁶⁵	PD = 62 Control = 62	Cross sectional case control	HAMD, HAMA	IL-1β, IL-6, IFNY, hsCRP, sIL-2R, TNF-α	In PD group, correlations between TNF-α r=0.345*, hsCRP r=0.393, sIL-2R r=0.452 and HAMD scores. Correlations with the same inflammatory markers and HAMA scores r=0.386* r=0.423*, r = 0.364*
Serum (with paired CSF)	Karpenko et al 2018¹⁵³	PD = 117, HC = 60	Cross sectional case control	BDI, HADS, NMSS	IL-1β, IL-1RA, IL-6, IL-10, TNF-α	Correlation between HADS anxiety score r = 0.42, HADS depression score r = 0.36 and serum IL-10 in PD. No significant associations found for CSF cytokines/other serum cytokines
Serum	Kim et al 2022¹⁶⁶	PD = 58 (45 at 3 year follow up), HC = 20)	Longitudinal cohort study	NMSS	IL-1β, IL-2, IL-6, IL-10, TNF-α, hsCRP	High PC3 (mainly loaded by IL-6 and IL-2) scores associated with worse NMSS over time. High PC3 was associated with aggravation of mood and apathy
Serum	Lindqvist et al 2012¹⁶¹	PD = 86, HC = 40	Cross sectional case control	FACIT, HAD, SCOPA-S	IL-6, TNF-α, sIL-2R, CRP	No significant correlations between non-motor symptoms and IL-6 or CRP. Regression analysis showed sIL-2R predicted FACIT scores β=−0.31, HAD depression scores β=0.36, and HAD anxiety scores β=0.32. TNF-α predicted HAD depression score β= 0.31 in analysis with an outlier.
Plasma	Menza et al 2010¹⁶³	PD = 52 (comorbid depression)	Cross sectional cohort	HAMD-17, PDQ-8, SF36, CGI, PSQI	IL-1β, IL-6, IL-10, TNF-α	TNF-α correlated with higher PSQI r=0.347, and HAMD-17 r= 0.44** scores. After adjusting for multiple comparisons, correlation between TNF-α and HAMD-17 remained significant.