Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinson's disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms...

...PD patients exhibited worse performance on nonmotor symptom scales (all P-values <0.001) and presented lower plasma levels of 5-HT (P < 0.001) and 5-HIAA (P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = -0.447, P < 0.001; r = -0.407, P < 0.001, respectively) and pain (r = -0.485, P < 0.001; r = -0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT (P = 0.01) and 5-HIAA (P = 0.006) remained significantly associated with depression.

Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD.
http://www.pubfacts.com/detail/26028...re-associated-

Neurology. 2015 Jun 16;84(24):2422-9.
2015 May 20.
Depression and subsequent risk of Parkinson disease: A nationwide cohort study.
Gustafsson H1, Nordström A1, Nordström P2.

Abstract
OBJECTIVE:
To investigate the long-term risk of Parkinson disease (PD) after depression and evaluate potential confounding by shared susceptibility to the 2 diagnoses.

METHODS:
The nationwide study cohort included 140,688 cases of depression, matched 1:3 using a nested case-control design to evaluate temporal aspects of study parameters (total, n = 562,631). Potential familial coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811 sibling pairs. Associations were investigated using multivariable adjusted statistical models.

RESULTS:
During a median follow-up period of 6.8 (range, 0-26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval [CI], 2.5-4.1) within the first year of depression, decreasing to 1.5 (95% CI, 1.1-2.0) after 15 to 25 years. Among participants with depression, recurrent hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1-1.9 for ≥5 vs 1 hospitalization). In family analyses, siblings' depression was not significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9-1.4).

CONCLUSIONS:
The time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for coaggregation among siblings all indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than 2 decades, depression may be a very early prodromal symptom of PD, or a causal risk factor.

© 2015 American Academy of Neurology.
http://www.ncbi.nlm.nih.gov/pubmed/25995056