Petra Maria Gaum

Exposure to polychlorinated biphenyls and the thyroid gland - examining and discussing possible longitudinal health effects in humans.

BACKGROUND Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. OBJECTIVES The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. METHODS A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. RESULTS There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. CONCLUSION This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation.

Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective

BACKGROUND Polychlorinated biphenyls (PCBs) are chemicals which were used for industrial purposes and are known to induce various adverse health effects. They are also known to be neurotoxic and numerous targets within the central nervous system have been identified in previous studies. Specifically, the neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as indicated in studies involving animals. However, limited evidence has been published documenting PCB induced changes in the neurotransmitter system in humans. OBJECTIVE In the present study, we examined the association between a higher PCB body burden following occupational exposure and possible changes in human neurotransmitter metabolites. METHODS Within a medical surveillance programme called HELPcB (Health Effects in High-Level Exposure to PCB) that monitors adverse health effects of occupational PCB exposure, urine samples were obtained (n(T1) = 166; n(T2) = 177 and n(T3) = 141). The urinary concentrations of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in order to determine the internal exposure to PCBs with human biomonitoring. RESULTS A cross-sectional analysis indicated a significant negative effect of PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to higher chlorinated PCBs was followed by constant reduced HVA level over three consecutive years. Exploratory analyses show different long-term effects for different PCBs according to their chlorination degree. A higher exposure with lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher exposure to all PCBs results in a reduction of HVA. CONCLUSION This study, to our knowledge, is the first to document changes in neurotransmitter metabolites after occupational PCB exposure in humans. This finding advances evidence obtained from past research, and identifies one potential pathomechanism in the central dopaminergic system of humans.

Effect of Occupational Polychlorinated Biphenyls Exposure on Quality-Adjusted Life Years Over Time at the HELPcB Surveillance Program

HELPcB (Health Effects in High-Level Exposure to Polychlorinated Biphenyls [PCB]) is a surveillance program for former PCB-exposed workers of a capacitor recycling company and other concerned individuals. The aim of this study was to examine the influence of polychlorinated biphenyls (PCB) on the health-related quality of life (HRQL) and on quality-adjusted life years (QALY). The EQ-5D-3L questionnaire was used to determine the HRQL. After three cross-sectional examinations at intervals of 1 yr, the longitudinal development of QALY was compared by repeated-measurement analysis of covariance (ANCOVA). The cohort was split at the 95th percentile of the comparison group for each PCB congener; known confounders such as age were taken into account. A significant difference in height and development of QALY over time was shown for the higher chlorinated non-dioxin-like PCB (hcPCB) congeners. A significant between-groups effect was found on PCB 153, PCB 180, and the sum of hcPCB. It was found that QALY decreased in the high-burden group and QALY stabilized after yr 2 in the normal-burden group. Taking the dimensions of the EQ-5D into account, the between-groups effect seems to be based predominantly on the dimension anxiety. The development of the within-group effect, however, seems to be based on the dimension mobility. This study detected a significant influence of hcPCB on the development of HRQL and QALYs over time according to the level of internal PCB burden.

Neuropsychological effects of occupational exposure to polychlorinated biphenyls

HighlightsA significant effect of PCBs on word fluency and sensorimotor processing is described.Lower chlorinated PCBs (LPCBS) have a negative impact on word generation.LPCBs are associated with a time‐on‐task effect in word fluency.Higher chlorinated PCBs and dioxin‐like PCBs show adverse effects on motor function.PCB‐induced neurotoxic effects on dopamine and norepinephrine are suggested. &NA; In the context of a health surveillance program for former PCB‐exposed workers of a transformer and capacitor recycling company in Germany, their family members, employees of surrounding companies and area residents a broad range of cognitive functions covering attention, executive processing, reasoning, memory and motor performance was examined. The study aimed at identifying potential adverse effects of PCB load on cognitive functions. Detailed analysis of PCB burden of the participants revealed rather high correlations of lower and higher chlorinated as well as dioxin‐like PCBs. Nearly one half of the participants exhibited increased burden in all three PCB classes whereas only 33 out of 237 participants did not show any increased PCB burden. Thus, data analysis followed a two‐fold strategy: (1) Based on studies providing data on PCB exposure of the German general population the PCB burden of every participant was classified as normal (percentile rank PR <95) or increased (PR ≥95). Increased burden with respect to lower (LPCBs) and higher chlorinated (HPCBs) as well as dioxin‐like (dlPCBs) PCBs was assumed if a participant showed at least one congener surpassing the PR95 criterion for the respective congener class and (2) Overall plasma PCB level per congener class was used as measure of PCB load. In a multivariate approach using structural equation modelling and multiple regression analysis we found a significant impact of PCBs on word fluency and sensorimotor processing irrespective of the measure of PCB burden (PR95 criterion or overall plasma level). However, no effect of PCB burden on memory, attention, and cognitive flexibility could be demonstrated. Particularly, an increase of LPCBs was associated with an overall reduction of verbal fluency of letter and semantic word generation as well as word production based on a single or two alternating criteria. In addition, participants with increased burden of LPCBs exhibited a time‐on‐task effect in terms of a stronger decline of performance with increasing duration of the verbal fluency task. Moreover, we found adverse effects of HPCBs on Aiming and of dlPCBs on Line Tracking. Results are discussed in terms of (1) a decrease of cerebral dopamine (DA) with non‐coplanar PCBs resulting in an impact on fronto‐striatal cerebral structures subserving verbal fluency and motor processing, (2) a PCB‐induced reduction of norepinephrine leading to the time‐on‐task effect with verbal fluency, and (3) adverse effects of PCBs on dopaminergic receptors in the cerebellum resulting in impaired fine motor function.

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

BackgroundExposure 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.MethodsThis 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.ResultsWe 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.ConclusionsThis 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.

A call for Applied Knowledge and Lived Interdisciplinarity in the medical care of depressed employees: a cross-sectional survey with German occupational physicians and psychotherapists

Objectives To identify approaches for an effective patient-centred care of depressed employees, we investigated occupational physicians’ (OPs) and psychotherapists’ (PTs) knowledge about job stressors on the development of depression, application of this knowledge, interdisciplinary cooperation and perceived barriers. Study design A cross-sectional online survey. Participants OPs (163; 48.5% male) and PTs (69; 43.5% male) providing complete data on the survey out of 257 OPs and 112 PTs who started the survey. There have been 458 (OPs) and 821 (PTs) initial clicks. Methods Main outcome measures were the importance ratings of specific job stressors, the frequency of asking patients about those stressors, the need for interdisciplinary cooperation, as well as perceived barriers for cooperation. We performed multivariate analysis of variance, intraclass correlation coefficients (ICCs) and Spearman’s rank-order correlations. Results The achieved response rate for OPs was 56.1% and for PTs 13.6%. Both disciplines agreed on the importance of job stressors regarding depression (ICC=0.90; 95% CI: 0.54 to 0.98), but both ranked these factors differently from the current state of research. As to knowledge application, OPs showed positive associations between the importance of job stressors and the frequency of asking employees about them (eg, job insecurity (rs=0.20, p=0.005)) and PTs for social stressors (eg, interpersonal conflicts (rs=0.38, p=0.001)). OPs (mean=3.41) reported a higher necessity of interdisciplinary cooperation than PTs (mean=3.17; F(1,230)=7.02, p=0.009). Furthermore, cooperation was reported as difficult to implement. PTs perceived barriers (eg, time restriction) as more hindering (mean=3.2) than OPs (mean=2.8; F(1,171)=8.16, p=0.005). Conclusions Both disciplines are aware of the relevance of job stressors as risk factors for depression, but should be encouraged to ask employees more frequently about them. The need for interdisciplinary cooperation and possible barriers are discussed. It is crucial to emphasise the meaning of sufficient cooperation, since closing this gap for improving patient-centred care especially for employees suffering from depression is necessary.