Neuropsychiatric symptoms and past manganese exposure in a ferro-alloy plant

Abstract

Introduction

Psychiatric manifestations have been reported in cases of manganism, and mood disorders are often observed in manganese (Mn) exposed workers. We examined neuropsychiatric symptoms among formerly Mn-exposed workers 14 years after cessation of exposure.

Materials and methods

A study was conducted in 1990 among workers from a ferro- and silico-Mn plant and unexposed working men referents from the same region in South-West Quebec. At follow-up in 2004, 77 former Mn-workers and 81 referents agreed to participate and responded to a neuropsychiatric symptom checklist, the Brief Symptom Inventory (BSI); scores were transformed into T-scores based on a normative population. Cumulated exposure indices (CEI) were computed for each former Mn-worker. Linear and logistic regression analyses were used.

Results

Mean T-scores were significantly higher among former Mn-workers than referents on scales of Depression and Anxiety. Mean T-scores of psychological distress increased with the CEI tertiles, with significant associations for the scales Somatization, Depression, Anxiety and Hostility. Former Mn-workers in the two highest tertiles of CEI showed a higher risk for T-scores ≥63 for Hostility (OR, 7.5; 95% CI, 1.5–38.9), Depression (OR, 2.6; 95% CI, 1.1–8.4) and Anxiety (OR, 3.0; 95% CI, 1.1–8.4).

Conclusion

These results suggest that past exposure to Mn may have lasting consequences on neuropsychiatric symptoms.

Introduction

Manganese (Mn) is an essential element, but exposure to high levels of airborne Mn in industries, such as mining, welding, Mn alloy, and dry battery production, can produce manganism, a neurodegenerative extrapyramidal syndrome with psychiatric features (Levy and Nassetta, 2003). The first symptoms of overexposure to Mn are irritability, fatigue, headache, muscle cramps, loss of appetite, apathy, and disorders of sleep and libido (Rodier, 1955). In the early reports on Chilean miners, a peculiar acute psychiatric syndrome, termed “locura manganica” or “manganese madness”, was described (Donaldson, 1987, Schuler et al., 1957). Characterized by compulsive or violent behaviours, emotional instability, disorientation, and hallucinations, this acute phase of intoxication could last for about a month and was clinically distinct from the chronic effects, which form a parkinsonian syndrome typified by muscular hypertonia, gait dysfunction with a propensity to fall backward, postural instability, bradykinesia, rigidity, micrographia, masked facies, speech disturbances and muscle tremors (Abdel-Naby and Hassanein, 1965, Chandra et al., 1974, Huang et al., 1989, Penalver, 1955, Rodier, 1955, Schuler et al., 1957).

Lower levels of Mn exposure among active workers are associated with neurofunctional alterations characterized by neuromotor and cognitive deficits, as well as mood changes (Iregren, 1990, Lucchini et al., 1995, Mergler and Baldwin, 1997, Mergler et al., 1994, Roels et al., 1985, Roels et al., 1992, Roels et al., 1987). In a review of studies of occupational exposure to Mn, Bowler et al. (1999) identified six dimensions of psychological effects: (1) anxiety, nervousness, irritability; (2) psychotic experience; (3) emotional disturbance; (4) fatigue, lack of vigor, sleep disturbance; (5) impulsive–compulsive behaviour; (6) aggression, hostility. Despite the importance of neuropsychiatric symptoms in mild and severe Mn intoxication, follow-up studies (Huang et al., 1998, Lucchini et al., 1999, Roels et al., 1999) have focused on the progression of neuromotor and/or cognitive deficits with little attention to mental health status.

Extensive human and animal data have shown high T1-weighted signal intensity on MRI, reflecting Mn accumulation in the basal ganglia, especially in the globus pallidus, among intoxicated humans and non-humans primates (Pal et al., 1999). Chronic exposure to Mn leads to selective dopaminergic dysfunction, neuronal loss, and gliosis in basal ganglia structures, with concurrent changes in astrocytes functioning. Alterations of content and metabolism of glutamate and γ-aminobutyric acid (GABA) activities have also been noted (Pal et al., 1999). A reduction in the content of serotonin in the putamen and globus pallidus was observed in non-human primates with chronic exposure to Mn (Eriksson et al., 1987). Deregulation of these neurotransmitter systems is known to play a role in several psychiatric diseases, including schizophrenia (Wassef et al., 2003), and in psychiatric symptoms of neurological diseases, such as Parkinson disease (Schrag, 2004). Although the mechanism of Mn toxicity and the resulting neurobiochemical changes are not completely understood, oxidative stress generated through mitochondrial perturbation is likely to be involved (Dobson et al., 2004). Unlike Parkinson's disease, Mn-induced damage probably occurs downstream of the nigrostriatal dopaminergic pathway (Shinotoh et al., 1997).

In 1990, our research team conducted a matched-pair, cross-sectional study on nervous system functions of workers from a Mn-alloy production plant (Mergler et al., 1994). The plant closed shortly after completion of the study, and in 2004, we conducted a follow-up the same cohort of formerly Mn-exposed workers and referents. The findings on neurobehavioural functions are reported elsewhere (Bouchard et al., in press). Here, we examine current neuropsychiatric symptoms in relation to past exposure to Mn.