Community Dent Oral Epidemiol 2011; 39: 1218 All rights reserved

2010 John Wiley & Sons A/S

Stressful negative life events and amalgam-related complaints

Sundstro m A, Bergdahl J, Nyberg L, Bergdahl M, Nilsson L-Go ran. Stressful negative life events and amalgam-related complaints. Community Dent Oral Epidemiol 2011; 39: 1218. 2010 John Wiley & Sons A S Abstract Objectives: The role of stressful life events in the onset of selfreported amalgam-related complaints is unclear. The aim of this study was to examine the relationship between life events and amalgam-related complaints. Method: The participants were selected from a longitudinal population-based study. One-to-one matching of 337 participants with amalgam-related complaints to 337 participants without such complaints was performed. For 81 of the participants with amalgam-related complaints and their matched controls, data was also available approximately 5 years before the onset of complaints, making longitudinal analysis possible. All participants completed questionnaires assessing the occurrence of 55 life events. Results: The results showed that many participants with amalgamrelated complaints experienced negative life events before and at the onset of amalgam-related complaints. They also reported more unexpected and uncontrollable events difcult to adjust to in comparison with controls. The groups did not differ on positive or neutral life events. Somatic illness or surgical operation was the most common life event. Death of a very close family member and a major change in nancial situation were also commonly reported. Conclusions: This study indicates that adverse negative life events could play a vital role in understanding and explaining amalgam-related complaints.

m1,2, Jan Bergdahl2,3,4, Anna Sundstro 1,5 Lars Nyberg , Maud Bergdahl3,4 and ran Nilsson1,6 Lars-Go
1 Centre for Population Studies Ageing and Living Conditions Programme, Umea , Sweden, 2Department of University, Umea University, Umea , Psychology, Umea Sweden, 3Institute of Clinical Dentistry, University of Troms, Troms, Norway, 4 Public Dental Service Competence Centre of Northern Norway (TkNN), Troms, Norway, 5Department of Radiation Sciences and Integrative Medical Biology Section, University, Umea , Sweden, Umea 6 Department of Psychology, Stockholm University, Stockholm, Sweden

Key words: amalgam related complaints, dental amalgam, dental material, life events, mercury Anna Sundstro m, Centre for Population Studies Ageing and Living Conditions University, S-901 87 Programme, Umea , Sweden Umea Tel.: +46-90-7866139 Fax: +46-90-7866958 e-mail: anna.sundstrom@ddb.umu.se Submitted 1 December 2009; accepted 25 June 2010

Dental amalgam has been a topic of concern since it was introduced more than 150 years ago in the practice of dentistry. The controversy has centred on the mercury content of amalgam and its potential health implications (14). Although small amounts of mercury can be detectable in the body, these levels are generally below recommended values (5), and published research has not reported evidence that dental amalgam has any adverse health effects, except in the rare event of mercury allergy (3, 68). Persons with self-reported reactions to dental amalgam experience a multitude of nonspecic emotional, somatic and cognitive symptoms that they attribute as symptoms of mercury intoxication or as mercury allergy (913). Commonly reported symptoms include memory disturbance, fatigue, muscle and joint pain, dizziness, headache, lack of concentration and general anxiety (10, 1218).

Furthermore, psychiatric comorbidity in patients with self-reported reactions to dental amalgam is high, ranging from 40% to 90%. Somatisation, anxiety disorders and depression are the most common psychiatric diagnoses (10, 19, 20). The causes of amalgam-related complaints are poorly understood, but a psychosomatic aetiology appears possible, and it has been suggested that these patients often have trouble expressing their emotions and instead react with bodily symptoms (21). For these patients, psychosocial factors, such as stressful life events, could play an important role in understanding their symptoms. In a study by Langworth et al. (22), negative life events were reported by a substantial number of patients (71%) at the time of the onset of symptoms. The most frequently reported life events were divorce, death or serious illness of a close relative, loss of employment and relocation. However, the
doi: 10.1111/j.1600-0528.2010.00571.x

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Negative life events & amalgam-related complaints

importance of these ndings and reports by other researchers (14, 21, 22) are limited either by small groups, or by lack of comparison to control groups. Because negative life events are also commonly reported among the general population, inclusions of well-matched controls are important for validation of data. Furthermore, most research comes from cross-sectional studies with no data before the onset of amalgam-related complaints, so interpretation of results can be difcult. Thus, it is unclear whether adverse life events can serve as a trigger of amalgam-related complaints. With this consideration in mind, this study extends previous research by examine the relationship between life events and amalgam-related complaints cross-sectionally and longitudinally in a population-based study.

Methods
Participants
This cross-sectional and longitudinal study is part of the ongoing Betula project, which is a population-based study focusing on ageing, memory and health. The Betula project has been described in detailed elsewhere (23, 24); therefore, only those aspects that are of relevance for this study will be summarized here. The Betula project currently consists of ve independent samples (S1S5) and involves a total of 4088 participants ranging in age at baseline between 35 and 85 years. All participants were randomly selected from the population registry in northern Sweden. Participants that had severe visual or auditory handicaps, mental retardation, dementia diseases or whose rst language was not Swedish were excluded from participation. The rst test wave was conducted in 19881990 with participants from S1, the second wave in 19931995 (S1, S2 and S3), the third in 19982000 (S1, S2, S3 and S4) and the fourth wave in 20032005 (S1, S3 and S5). Participants in this study were from all sample (S1, N = 104; S2, N = 91; S3, N = 90; S4, N = 29; and S5, N = 28), and all test waves (T1, N = 56; T2, N = 171; T3, N = 75; and T4, N = 40). All participants were examined at two sessions, approximately 1 week apart. In the rst test session, a trained nurse conducted an extensive health examination and an interview of health status. Participants were also given questionnaires concerning various social variables and life events to ll in at home and return for the next session. In

the case of an incomplete questionnaire, the participant was assisted in completing it. The present analyses were based on those participants who responded afrmatively on the question: Do or did you have health problems you think are related to amalgam llings?. This question was included in the health interview and was conducted by a trained nurse in the rst test session. A total of 346 participants (8.5%) reported that they had health problem that they related to their dental amalgam llings. Nine of these participants had missing data on life events and were therefore excluded. This exclusion resulted in a sample of 337 individuals with self-reported amalgam-related complaints (amalgam group). A control group (n = 337) matched one-by-one for age, gender, education, test sample and test wave was also selected from the same population and included in the cross-sectional sample. Participants in the cross-sectional analysis were from all samples and all test waves. Most participants in the amalgam group reported amalgamrelated complaints in their rst test. However, some participants (n = 81) had, in a previous test wave, answered no to the question about amalgam-related complaints, and reported no problems related to amalgams. For example, one participant in Sample 1 (S1) reported no amalgam-related complaints during his or her rst test wave between 1998 and 1990 (T1), but 5 years later during his or her second test wave (T2), reported having amalgam-related complaints, thus making a longitudinal analysis possible between T1 and T2. One other participant was from Sample 3 (S3) and did not report any complaints during his or her rst test occasion (T2) between 1993 and 1995, but 5 years later reported complaints, thus making longitudinal analysis possible between T2 and T3. Consequently, both of these participants had pre data, which make a within-subject comparison possible. The 81 participants with data available before the onset of amalgam-related complaints were, together with their 81 one-by-one-matched controls, enrolled in the longitudinal analysis.

Measures
The Life Event Inventory is a record developed by Perris (25) and was used to measure life events. The inventory consists of 55 specic life events and covers categories such as areas of work, private life, social relationship, health, relatives and friends and the death of a relative or close friends. Participants were asked to indicate if each event had occurred

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or not during the last 5 years. In addition, the participants were asked to note whether the event was expected not expected and also to rank how they experienced the event: very negative, negative, neutral, positive, or very positive. Thus, one participant could report the occurrence of a major life event and rate the impact of the event as neutral while another participant, experiencing the same event, could rate it as very negative. Participants were also asked to note the degree of control that they had over the events occurrence (control no control) and, nally, the adjustment (easy difcult) that was required to each reported event.

Self-reported health status

Health status was assessed by a self-reported health status questionnaire. Participants were asked if they fell well or not (yes no) and if they had the following symptoms: heart chest problem, back pains, stomach ace, constipation, aching joints, skin problem, airway problem, aching shoulders, arms, or legs, short of breath, oedema legs, dizziness, loss of appetite, urinating problems, sleeplessness, fatigue, depression, loneliness, anxiety, visual problem and auditory problem.

was 24%. The difference was statistically signicant (P < 0.001). Participants with amalgam-related complaints also reported more symptoms than controls. The mean number reported symptoms for those with amalgam-related complaints was 5.4 (SD = 3.3), compared with 3.6 (SD = 2.8) for controls (P < 0.001). The symptoms that both participants with amalgam-related complaints and controls most commonly reported were aching shoulders, arms, or legs, back pains, aching joints and fatigue (Table 2). Participants with amalgamrelated complaints were also more likely to report multiple symptoms. Twenty-six per cent among the amalgam group report having eight or more symptoms, compared to nine per cent among controls (P < 0.0001). Furthermore, depressive symptoms, such as loss of appetite, sleeplessness, fatigue, feeling of depression, loneliness, and anxiety, were also commonly reported in the amalgam group and signicant at P < 0.001 (Table 3).

Life events
Participants with amalgam-related complaints reported a total of 1933 life events, and controls reported a total of 1573 events. The mean occurrence of events per person was 5.7 (SD = 4.9, range 030) for amalgam group, and 4.7 (SD = 3.9, range
Table 1. Baseline characteristics of participants with selfreported amalgam-related complaints and controls Amalgam group Controls (N = 337) (N = 337)

Statistical Analysis
Demographic data was analysed by the McNemars test, and continuous variables were compared using the paired t-test or Wilcoxon signed rank test. All statistical tests were two-tailed with the critical P-value set at 0.05 and carried out using SPSS version 15.0 for Windows (SPSS Inc, Chicago, IL, USA).

Characteristics Women, % Age, mean SD Education SDb Smoking status Current smoker, % Employment statusa,b Employed, % Unemployed, % Studying, % Early retirement, % Age retirement, % Sick-listed, % Marital statusb Not married, % Married, % Divorced, % Widow widower, % Psychiatric disorders, %

P-value

65.6 65.6 NS 58.8 12.2 58.8 12.2 NS 10.4 3.8 10.3 3.7 NS 44.5 44.8 3.3 3.6 13.4 36.2 8.0 6.4 70.1 13.4 10.1 13.4 43.3 51.3 1.2 3.0 5.0 35.6 4.1 5.2 75.1 6.7 13.1 5.6 NS NS NS NS <0.05 NS <0.05 NS NS NS NS 0.001

Results
Characteristics of participants with self-reported amalgam-related complaints and matched controls (age, gender, education, test sample and test wave) are presented in Table 1. Groups were similar in terms of most baseline characteristics. However, more cases than controls had had an early retirement, were sick-listed, and they were also more likely to report a psychiatric disorder (past or current).

Self-reported symptoms
Among participants with self-reported amalgamrelated complaints, 42% reported that they did not feel well. The corresponding gure among controls

Notes: aPercentages are sum to more than 100% because participants could mark more than one employment status category. b Missing values: 3 for education, 2 for employment status, 17 for marital status.

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Negative life events & amalgam-related complaints Table 2. Frequencies of symptoms in participants with self-reported amalgam-related complaints and controls Symptoms Heart chest problem, % Back pains, % Stomach ace, % Constipation, % Aching joints, % Skin problem, % Airway problem, % Aching shoulders, arms, or legs, % Short of breath, % Oedema legs, % Dizziness, % Loss of appetite, % Urinating problems, % Sleeplessness, % Fatigue, % Depression, % Loneliness, % Anxiety, % Visual problem, % Auditory problem, % Amalgam group 74 (22.0%) 169 81 40 165 85 93 220 51 70 81 12 47 96 158 64 35 89 98 98 Controls 49 (14.5%) P-value 0.026

(50.1%) 103 (30.6%) <0.001 (24.0%) 51 (15.1%) 0.004 (11.9%) 19 (5.6%) 0.004 (48.8%) 100 (29.7%) <0.001 (25.2%) 62 (18.4%) 0.032 (27.6%) 65 (19.3%) 0.011 (65.3%) 163 (48.4%) <0.001 (15.1%) (20.8%) (24.0%) (3.6%) (13.9%) (28.5%) (46.9%) (19.0%) (10.4%) (26.4%) (29.1%) (29.1%) 48 47 49 4 33 67 98 36 27 59 60 87 (14.2%) NS (13.9%) 0.019 (14.5%) 0.002 (1.2%) 0.043 (9.8%) NS (19.9%) 0.009 (29.1%) <0.001 (10.7%) 0.002 (8.0%) NS (17.5%) 0.005 (17.8%) 0.001 (25.8%) NS

Table 3. Prevalence of symptom of depression Amalgam group Depression symptom No depression symptom Total 219 (65.0%) 118 (35.0%) 337 (100%) Controls 164 (48.7%) 173 (51.3%) 337 (100%)

Table 4. Mean number of experienced life events in participants with self-reported amalgam-related complaints and controls Life events Very positive life events, mean SD Positive life events, mean SD Negative life events, mean SD Very negative life events, mean SD Amalgam group 0.82 1.5 1.08 1.2 1.50 1.7 1.43 2.1 Controls 0.81 1.5 0.99 1.2 1.00 1.3 1.04 1.6 P-value NS NS <0.001 0.004

023) for controls (P < 0.01). The absence of experienced life events was reported by 8.0% of amalgam group and 10.4% of controls. The most frequently occurring event in the amalgam group was somatic illness or surgical operation (41%), close relative died (26%), major change in nancial

state (26%), close relative severely ill (21%), quit paid work, e.g. age retirement (20%) and moved to another house (20%). Among controls, the most commonly reported events were somatic illness or surgical operation (27%), important changes at work, e. g. new co-workers (24%), close relative died (23%), participated in an educational course (20%) and changes in working responsibility, i.e. more responsibility (19%). The occurrence of events that was ranked as very positive, positive or neutral was not statistically different between amalgam group and controls. In contrast, events ranked as negative or as very negative were more frequently reported in the amalgam group compared to controls. The difference was signicant at P < 0.01 (Table 4). Participants with amalgam-related complaints experienced a total of 985 events that they ranked as negative or very negative. The corresponding frequency of negative or very negative events for controls was 690 events. The mean occurrence of negative very negative events was 2.9 for amalgam group (SD = 3.2, range 020) and 2.0 for controls (SD = 2.2, range 011). The difference was signicant at P < 0.001. Even if the amalgam group reported more negative very negative events in relation to controls, the difference reached signicance for only ten events: quit paid work, trouble with co-workers, unemployed more than 1 month, major change in nancial state, changes in sexual habits, close friend died, somatic injury, somatic illness or operation, large debts and major changes in social network (Table 5). The distribution of the number of negative very negative events per person differed signicantly between persons with amalgam-related complaints and controls (P < 0.001), see table 6. Twelve persons with amalgam-related complaints and one of the controls experienced 11 or more negative very negative life events. The highest numbers of events per person reported were 20 for the amalgam group and 11 for controls. The amalgam group reported also more often that the experienced life event was not expected (P < 0.001), and that they had lower control over the event (P < 0.001). They also reported more frequent, compared to controls, that the adjustment to the event was difcult (P < 0.01).

Before onset of amalgam-associated complaints

For 81 participants with amalgam-related complaints and for their matched (age, gender, education, test sample, and test wave) controls, data

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 m et al. Sundstro Table 5. Signicant negative very negative life events in participants with self-reported amalgam-related complaints and controls Life events Quite paid work Trouble with co-workers Unemployed more than 1 month Major change in nancial state Changes in sexual habits Close friend died Somatic injury Somatic illness or surgical operation Large debts Major changes in social network Amalgam group 21 (6.2%) 30 (8.9%) 17 (5.0%) 54 (16.0%) 27 (8.0%) 50 (14.8%) 47 (13.9%) 89 (26.4%) 20 (5.9%) 26 (7.8%) Controls 6 (1.8%) 17 (5.0%) 6 (1.8%) 28 (8.3%) 11 (3.3%) 32 (9.5%) 27 (8.0%) 46 (13.6%) 9 (2.7%) 13 (3.9%) P-value 0.003 0.049 0.020 0.002 0.008 0.034 0.014 <0.001 0.037 0.032

(SD = 4.6). Controls reported a mean of 3.9 (SD = 3.0) events at rst occasion of assessment, and 4.6 (SD = 3.1) events at the second occasion of assessment. There was a signicant difference between participants with amalgam-related complaints and controls with regard to the mean negative very negative events experienced per person before onset of complaints (P < 0.001). There was no within-group difference for the repeated measurements of negative events. The participants with amalgam-related complaints reported a mean of 3.0 (SD = 3.5) negative very negative events before onset of symptoms, and 3.1 (SD = 3.1) negative very negative events at onset of symptoms, whereas controls reported a mean of 1.5 (SD = 1.6) versus 2.0 (SD = 1.9) events, respectively.

Table 6. Distribution of the number of negative very negative events in participants with self-reported amalgam complaints and controls Number of negative life events 0 15 610 11 or more Amalgam group 77 202 46 12 (22.9%) (59.9%) (13.6%) (3.6%) Controls 105 205 26 1 (31.2%) (60.8%) (7.7%) (0.3%)

Discussion
This study combines both cross-sectional and longitudinal design to examine the relationship between life events and self-reported amalgamrelated complaints in a population-based study. The results show that participants with amalgamrelated complaints, when compared to controls, report signicantly more negative life events, and, for some the onset of those complaints was preceded by a longer period of at least 5 years of negative life events. In comparison with controls, participants with amalgam-related complaints experienced not only a higher number of negative life events but also more unexpected and uncontrollable events causing adjustment difculties. However, life events ranked as positive or neutral were not associated with amalgam-related complaints. Similar ndings linking major negative life events of patients to amalgam complaints were reported in previous studies (14, 21, 22). Our clinical observations support these results in that persons with amalgam-related complaints often report experiencing a large number of stressful events. Experiencing the loss of something valuable, for example the loss of a loved person or a job, is considered the main trigger factor of psychological stress (26). In this study, experience of loss was one of the events that differentiate between persons with amalgam-related complaints and controls. Loss of health, job and death of a close family or friend were some of the major sources of distress that persons with amalgamrelated complaints reported.

prior to onset of amalgam-related and reported complaints were available. These 81 participants reported initially no complaints, but 5 years later they reported that they had amalgam-related complaints. Data shows that the amalgam group had a mean of 4.9 (SD = 3.2) self-reported symptoms before the onset of amalgam-related complaints, and 5.5 (SD = 3.4) symptoms at the test occasion after the onset. The difference was not signicant. Matched controls for the same period reported a mean of 3.6 (SD = 2.7) symptoms at rst occasion, and 3.6 (SD = 2.9) at the second occasion of assessment. The amalgam group had a signicant higher frequency of life events, compared to controls, before onset of amalgam-related complaints (P < 0.01). No difference within-groups for the repeated measurement of life events was observed for neither group. Before onset of amalgam-related complaints, participants reported a mean of 5.6 (SD = 4.8) events. At the second occasion, when they reported amalgam-related complaints, the mean number of events for this group was 6.0

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Negative life events & amalgam-related complaints

Previous researches have found that stressful life events can trigger a large number of unspecic physiological symptoms, somatic disorders, infectious diseases, psychological problems and disorders (2730). Moreover, negative life stressors are often associated with anxiety and depression symptoms, which may in turn generate somatic symptoms (28). In this study, persons with amalgam-related complaints reported signicantly more depressive and anxiety symptoms, than controls, which can be interpreted as a reaction to the negative life events reported. The way individuals utilize coping mechanisms and social support to handle stressful life events is an important predictor of the outcome, in this case health consequences that are because of stressful life events (26). Previous studies have noted that persons with amalgam-related complaints tend to react to stressful life events in a maladaptive manner with a weak self-image and a low stress tolerance threshold (31). Gottwald et al. (20) found that persons with amalgam complaints use a more vigilant coping style when faced with environmental threats by actively seeking out threatening information to reduce the uncertainty. This coping style has been suggested to lead to a rather ruminative focus on the potential negative health effects of amalgam (20). The specic cognitive style has been considered similar to that of psychosomatic patients (10, 22, 31, 32). People suffering from depressive disorders or depressive symptoms might be more vulnerable to negative life events because of their behaviours than are people without these problems (33, 34). These stressful events can worsen depression, creating a downward spiral of depression and stress. The amalgam group also commonly reported a current or previous history of psychiatric disorders. However, because most participants did not have longitudinal data, no causal conclusion can be drawn regarding the direction of the relationship between negative life events and mood and anxiety disorders. Nevertheless, there is strong evidence that negative life event stressors are risk factors for the development of psychiatric diagnoses such as mood and anxiety disorders (35). One strength of this study is that data was selected from a general population rather than from a clinical sample, thereby making the results more generalizable. The prospective design of this study also provides information about the events occurring before the onset of complaints, thus making it possible to compare stressful life events

before and at onset of complaints. Another strength include the close matching of cases to controls groups regarding age, gender, education, test sample and test wave. However, it is important to bear in mind that the amalgam group is recognized to represent a very heterogeneous group (22), and this seems to be the case in our study as well. When interpreting the results from this study, it should be noted that not all of the participants with amalgam-related complaints experienced a high number of negative life events. One important limitation of this study is its lack of clinical data, such as the number of amalgam surfaces and mercury levels in body uids. However, other studies have not found any difference between patients with amalgam-related complaints and controls in the number of amalgam llings and mercury levels in body uids (10, 22, 31, 36). Another limitation is the use of self-reported data. Self-reported data might be affected by response biases. We believe, though, that the data are accurate because both groups recall approximately the same number of neutral and positive life events. Therefore, the difference in the recall between negative and very negative events seems to be warranted. Taken together, persons with amalgam-related complaints appear to experience a longer period of psychological stress, in terms of negative life events, which indicates that stressful life events could play a vital role in understanding amalgam-related complaints. These ndings underscore the importance of a multidisciplinary approach to the treatment of people with amalgam-related complaints.

Acknowledgements
The Betula Study is funded by the Bank of Sweden Tercentenary Foundation (1988-0082:17), Swedish Council for Planning and Coordination of Research (D19880092, D1989-0115, D1990-0074, D1991-0258, D1992-0143, D1997-0756, D1997-1841, D1999-0739, B1999-474), Swedish Council for Research in the Humanities and Social Sciences (F377 1988-2000), Swedish Council for Social Research (1988-1990: 88-0082, 311 1991-2000, 345-20033883 and 315-2004-6977), the National Board of Health and Welfare, Sweden (00-3343 2006) and Alzheimer Foundation; Sweden (2007 2-116).

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