Suicides in persons suffering from rheumatoid arthritis

M. Timonen1,2,, K. Viilo1, H. Hakko1, T. Särkioja3, M. Ylikulju1, V. B. Meyer-Rochow4,5, E. Väisänen1 and P. Räsänen1

1 University of Oulu, Department of Psychiatry, BOX 5000, 90014 University of Oulu,
2 Health Centre of Oulu, Box 8, FIN-90015 City of Oulu,
3 University of Oulu, Department of Forensic Medicine, BOX 5000, 90014 University of Oulu,
4 Department of Physiology, University of Oulu, Oulu, Finland and
5 International University Bremen (IUB), School of Engineering & Science, D-28725 Bremen, Germany


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To assess the demographic and psychosocial profiles of patients with rheumatoid arthritis (RA) who committed suicide. Two control groups were used: osteoarthritis (OA) and suicide victims with neither RA nor OA.

Method. A study based on a prospective, 13-yr follow-up database with linkage to national hospital discharge registers of all suicides (1296 males, 289 females) committed during the years 1988–2000 in the province of Oulu situated in northern Finland.

Results. Females were significantly over-represented among RA patients who committed suicide (52.6% RA women vs 17.3% women with neither RA nor OA). Comorbid depressive disorders preceded suicides in 90% of the female RA patients. Before their suicide, 50% of the female RA patients (vs 11% of the male RA patients) had experienced at least one suicide attempt. The method of suicide was violent in 90% of the RA females. RA males were less often depressive, but committed suicide after experiencing shorter periods of RA and fewer admissions than females.

Conclusion. Attempted suicides and especially depression in female RA patients should be taken more seriously into account than previously in clinical work so that the most appropriate psychiatric treatment can be provided for such patients.

KEY WORDS: Rheumatoid arthritis, Osteoarthritis, Suicide, Depression.


    Introduction
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Suicidal ideation, considered to be a core symptom of major depression [1], is also seen among patients suffering from physical illnesses [2, 3]. It has even been stated that suicidal ideations, occurring in somatic patients, may arise from a comorbid depression [4].

Rheumatoid arthritis (RA) is a somatic disorder, which is known to be associated with major depression, and prevalences exceeding even 40% have been reported [5, 6]. Recently, Treharne et al. [7] showed that 11% of hospital out-patients with RA had experienced suicidal ideation. In addition, the same authors found a clear gender difference with 14% of the female RA patients reporting suicidal ideations compared with only 3% of the male patients. To identify comprehensively suicidal risks of patients suffering from RA [7], additional information on demographic, physical and psychosocial profiles was called for. Furthermore, there exist no studies to date that indicate what proportion of patients with RA, harbouring suicidal ideations or having previously attempted suicide, actually succeed in committing suicide.

A large, population-based, 13-yr database for all suicides committed during 1988–2000 in northern Finland enabled us to compare the demographic and psychosocial profiles between suicide victims with and without RA.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
We analysed all suicides (n=1585) committed during the years 1988–2000 in the province of Oulu in northern Finland. The annual mean population of the province of Oulu was approximately 445 000 over the study period. The suicide data for this study were extracted from official death certificates, which were based on forensic medico-legal investigations. The study protocol was approved by the Ethical Committee of Oulu University.

All hospital admissions of suicide victims until the end of 1999 were obtained from the Finnish Hospital Discharge Register (FHDR), which is maintained by the Finnish National Board of Health, and from the Hospital Care Register, kept by the National Research and Development Centre for Welfare and Health. The FHDR covers all treatment in general, private, mental, military and prison hospitals, as well as the in-patient wards of local health centres nationwide. It contains the personal and hospital identification code, and data on age, gender, length of stay and primary diagnosis at discharge, together with three subsidiary diagnoses. The FHDR has been found to be a valid source of information in epidemiological research [8, 9].

The study population consisted of those suicide victims who had suffered from hospital-treated RA. Two control groups were formed: the first contained victims with an additional chronic hospital-treated disease, namely osteoarthritis (OA), and the other included the remainder of the suicide victims, who had had neither RA nor OA. The diagnoses of hospital-treated RA (International Classification of Diagnoses, ICD-8: 712.00–712.50; ICD-9: 714; ICD-10: M05, M06) and OA (ICD-8: 713; ICD-9: 715; ICD-10: M15–M19) of suicide victims were extracted from the FHDR. Of all the suicide victims, 19 had suffered from RA, 49 from OA and 1517 subjects had had neither of these disorders.

In order to assess the possible link between RA and comorbid psychiatric disorders, the following hospital-treated psychiatric disorders were extracted from the FHDR: depression (ICD-8: 2960, 2980, 3004; ICD-9: 2961, 2968, 3004; ICD-10: F32–F34.1), psychotic disorders (ICD-8: 295–299; ICD-9: 295, 2961–4E, 2967A, 297, 298, 2990, 2999; ICD-10: F20-25, F28, F29, F30.2, F31.2, F31.5, F32.3, F33.3) and psychiatric diagnoses (e.g. non-psychotic and non-depressive disorders) other than the ones mentioned above.

Information about alcohol use, suicide methods and previous suicide attempts was extracted from the official death certificates. Suicide was defined as being committed under the influence of alcohol if acute alcohol intoxication was detected in the medical autopsy. Furthermore, the method of suicide was considered as violent if the suicide was committed by hanging, shooting, drowning, wrist-cutting, traffic or jumping from a high place. Correspondingly, non-violent suicide methods were poisoning and gas [10].

Differences in categorical variables between subgroups were investigated by Pearson's {chi}2-test. Mann–Whitney's (M–W) U-test was used to assess subgroup differences in continuous variables because of their skewed distributions. The statistical software used was the SPSS for Windows, version 9.0.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
In the whole study population (n=1585), 18.2% (n=289) of the suicide victims were females. The proportion of female suicide victims was statistically significantly higher in the RA population (52.6%) only when compared with victims who had suffered neither from RA nor OA (17.3%) ({chi}2=16.0, d.f.=1, P<0.001). It was not significantly higher when compared with victims with OA (32.7%) ({chi}2=2.3, d.f.=1, P=0.128).

The average (median) age of the suicide victims at the time of suicide was also significantly higher in RA patients (61.7 yr) when compared with victims with neither RA nor OA (41.3 yr) (M–W U-test, P<0.001), but it was not higher when compared with victims with OA (61.9 yr) (M–W U-test, P=0.416). However, when both genders were analysed separately, the only statistically significant age difference was seen between females with RA (65.5 yr) and victims with neither RA nor OA (45.5 yr) (M–W U-test, P<0.001) (Table 1Go).


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TABLE 1. Hospital-treated psychiatric disorders, alcohol use at the time of the suicide, and suicide method among male and female suicide victims with rheumatoid arthritis (RA), osteoarthritis (OA) and among subjects without either of these diseases

 
Table 1Go shows sex-specific prevalences of hospital-treated mental disorders and the use of alcohol at the time of the suicide as well as the type of suicide method in victims with and without RA. In females, the proportion of comorbid hospital-treated depression was statistically significantly higher among RA females (80.0%) than OA females (31.3%) ({chi}2=5.9, d.f.=1, P=0.016) and females with neither RA nor OA (30.8%) ({chi}2=10.6, d.f.=1, P=0.001). Furthermore, 90% of the female RA patients had chosen a violent suicide method, but only 35.5% of OA female victims ({chi}2=6.9, d.f.=1, P=0.008) and 56.3% of those with neither RA nor OA had done so ({chi}2=4.5, d.f.=1, P=0.034).

Regarding male suicide victims, the only statistically significant difference was seen in the choice of suicide method: all men with RA had chosen a violent suicide method, while the respective proportion among victims with OA was 66.7% ({chi}2=4.1, d.f.=1, P=0.044).

The demographic and psychological descriptions of each RA suicide victim in this study are presented in Table 2Go. We found that the time interval between the first admission because of RA and the act of suicide was statistically significantly lower in males than in females (median 3.2 yr in males, 14.9 yr in females; M–W U-test, P<0.001). Second, the median number of RA admissions was lower in males than in females (one vs six admissions, M–W U-test, P=0.095).


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TABLE 2. Sociodemographic and clinical characteristics of the 19 rheumatoid arthritis suicides

 
The time interval between the last hospital admission for any disorder and the suicide was statistically significantly lower in females than in males, 0.7 months and 10.5 months, respectively (M–W U-test, P=0.008). Among females, 60% of the last hospital admissions preceding the suicide had occurred because of psychiatric reasons. During their lifetimes, all females had suffered from at least one comorbid psychiatric disorder (information obtained either from the FHDR or from the death certificates). Furthermore, 90% of females had suffered from some form of depressive disorder. Based on the information extracted from the death certificates, 50% of the females (vs 11% of the males) had attempted to commit suicide at least once prior to the completed suicide.


    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Our main finding was that 50% of those with RA, who committed suicide, were female, although only 18% of the whole suicide population were female. In addition, 90% of the female RA victims were found to have suffered from comorbid depression, which is in line with previous findings suggesting that suicidal ideation among somatic patients arises from the comorbid depression [4]. It is, in fact, well known that suicide is the most severe manifestation of major depression.

Neuroendocrine studies have shown that an impaired central serotonin metabolism is associated with the pathogenesis of depression [11]. In addition, several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are also involved in depressive disorders with both concomitant suicidal behaviour [12, 13] and violent suicide method [14]. Thus, it is reasonable to assume that 90% of the female RA victims in this study chose violent suicide methods because of a dysfunctional serotonin metabolism in the brain as a result of depression [10].

As reviewed previously, dietary fatty acids—especially polyunsaturated fatty acids (PUFAs)—can have important effects on inflammatory processes [15, 16]. PUFAs are either precursors of eicosanoids, such as prostaglandins, or affect eicosanoid and cytokine formation. An increased ratio of omega-6 to omega-3 PUFAs may lead to an overproduction of inflammatory cytokines and eicosanoids. On the other hand, inflammatory cytokines have been found to provoke symptoms similar to those found in major depression, and when administered peripherally or centrally they alter serotonin metabolism in the brain. Thus, changes in fatty acid intake/metabolism may be behind some aspects of the pathophysiology of both RA and depression, explaining at least partly our findings [1519].

Furthermore, pro-inflammatory cytokines are known to be able to activate the hypothalamic–pituitary–adrenal (HPA) axis and they can also induce resistance against the actions of glucocorticoid hormones by influencing glucocorticoid receptor expression as reviewed by Maes and Smith [15]. Hypercortisolism and dysfunction of corticosteroid receptors are usually present in depression [2022], but on the other hand, atypical depression is known to be characterized by underactivity of the HPA axis [23]. In addition, it has been noted that there are also alterations in the function of the HPA axis in RA patients [24, 25], females being more dependent on the HPA axis than males [26]. Thus, the HPA axis might be involved severely enough in the body–mind interactions of RA and depression to lead to suicide and this may also be the explanation for the finding of the gender difference in our study.

Men committed suicide after a shorter duration than women following the first admission for RA. In contrast with women, only a few men had comorbid psychiatric disorders. It has been noted previously that a physical illness can also be a strong predictor of suicide [27, 28]. RA is a long-term somatic disease often followed by chronic pain, disability and psychosocial stress, which themselves might have a complex and bi-directional association with depression [29]. As reviewed by Epperly and Moore [30], for example, alcohol abuse and violent behaviour can also be signs of psychosocial distress in men. In this study, alcohol contributed to suicide in over 40% of RA males compared with 10% of RA females. Thus, we speculate that in male RA patients, the psychosocial distress may become manifest as ‘masked depression’—i.e. self-violent behaviour and alcohol problems—and therefore be difficult to recognize in clinical practice. Therefore, all diagnostic tools should be recruited to identify possible depression in RA patients in order to provide adequate treatment for them. For example, selective serotonin re-uptake inhibitors could be recommended earlier for this patient population [31], since these drugs have been shown to be effective in placebo-controlled studies in patients with major depression with comorbid alcohol-abuse disorders [3234].

The limitation of our study was that owing to the study design we could not test the causal hypothesis: we do not know whether suffering from RA is causing depression or vice versa. Second, we were not able to use a live RA population (also including out-patients) as a reference group. The case definition of RA patients was based on hospital admissions and only those with RA severe enough to warrant hospital admission were included in the study group of RA patients. Consequently, the actual number of hospital-treated RA subjects was relatively low, although the data were gathered over the rather long period of 13 yr. It must also be noted that we do not know how many control subjects were treated as out-patients, but not in-patients, for RA. Furthermore, in Finland, the incidence of clinically significant RA was shown to be about 40 per 100 000 in the adult population, which is in accordance with the corresponding prevalence figure of about 0.8% [35, 36]. Thus, owing to the relatively uncommon occurrence of RA patients in the general Finnish population and the fact that only the most severe manifestations of RA are treated in hospitals, a notably higher proportion of RA patients was present in our suicide database for both genders. Despite these limitations, we consider our findings important, and suggest that the study should be replicated with larger databases and different study populations.


    Acknowledgments
 
This study was supported by grants from the Research Foundation of Orion Corporation and the Sigrid Juselius Foundation.


    Notes
 
Correspondence to: M. Timonen, Health Center of Oulu, Box 8, FIN-90015 City of Oulu, Finland. E-mail: markku.timonen{at}oulu.fi Back


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Submitted 29 January 2002; Accepted 2 August 2002