Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program

Abstract

Background: Exposure to polychlorinated biphenyls (PCBs) is associated with depressive symptomatology. A cause of depressive symptoms is a disturbance in the neurotransmitter system of dopamine (DA). Animal as well as human studies report that PCBs can influence the DA system. This study examined whether PCB-related depressive symptoms are affected by DA metabolites in humans with high PCB body burden.

Methods: This study is part of the German HELPcB surveillance program (Health Effects in high Level exposure to PCB) for occupationally exposed workers and their relatives. Data was collected from 178 participants on two measurement time points (t1 and t2) with a one-year time lag in between the two time points. PCBs were analyzed in plasma via human biomonitoring and a validated questionnaire was used to identify existence and severity of depressive symptoms. As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test whether the association between PCB exposure and severity of depressive symptoms is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation was tested with the SPSS macro MEDIATE.

Results: We found a significant mediation over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The positive association between PCB exposure with severity of depressive symptoms was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was associated with lower concentration in urinary HVA. A reduced HVA concentration at t1 was correlated with increased depressive symptoms severity at t2. No meditations were found for VMA.

Conclusions: This work indicates that the association of PCB exposure and an increase of depressive symptoms after one year is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps towards finding an explanation for an underlying neurochemical pathomechanism of PCB-related depressive symptomatology.

Keywords: Adults; Depressive symptoms; Dopamine; Homovanillic acid; Humans; Neurotoxicity; Neurotransmitter metabolites; Polychlorinated biphenyls; Vanillylmandelic acid.

Fig. 1

Hypothesized mediation model with direct and indirect path

Fig. 2

Flow-chart of the number of the study population. Note: t1 = measurement occasion 1, t2 = measurement occasion 2. ¹excluded due to dopamine relevant medication, such as antidepressants or medication in Parkinson disease

Fig. 3

Illustration with standardized-b-coefficients of the longitudinal indirect paths of PCB to depressive symptoms through HVA/crea. Note: HPCB = higher-chlorinated PCBs, dioxin-like PCBs, HVA = homovanillic acid, t1 = measurement occasion 1, t2 measurement occasion 2; ⁺ = p < .10 (1-sided), * = p < .05 (1-sided)