Department of Psychiatry, Vrije Universiteit Amsterdam, The Netherlands
Department of Psychiatry and Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, The Netherlands
Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam, The Netherlands
Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Correspondence: R. A. Schoevers, Department of Psychiatry, Vrije Universiteit Amsterdam, Valeriusplein 9, 1075 BG Amsterdam, The Netherlands. Tel: 00-31-20-4446770; Fax: 00-31-4446775; e-mail: RA.Schoevers.emgo{at}med.vu.nl
Declaration of interest Grants from the Netherlands Health Research Programme and the Netherlands Fund of Mental Health (see Acknowledgements).
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ABSTRACT |
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Aims To investigate the association between major and mild depressive syndromes and excess mortality in community-living elderly men and women.
Method Depression (Geriatric Mental State AGECAT) was assessed in 4051 older persons, with a 6-year follow-up of community death registers. The mortality risk of neurotic and psychotic depression was calculated after adjustment for demographic variables, physical illness, cognitive decline and functional disabilities.
Results A total of 75% of men and 41% of women with psychotic depression had died at follow-up. Psychotic depression was associated with significant excess mortality in both men and women. Neurotic depression was associated with a 1.67-fold higher mortality risk in men only.
Conclusions In the elderly, major depressive syndromes increase the risk of death in both men and women, but mild depression increases the risk of death only in men.
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INTRODUCTION |
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METHOD |
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Baseline measures
A 1-hour interview was developed to gather information on psychiatric
symptoms, demographic and medical status, previous history and family history.
The interview consisted of the Dutch translation of the Mini-Mental State
Examination (MMSE; Folstein et
al, 1975), all Geriatric Mental State (GMS) items related to
organic, affective and anxiety syndromes
(Copeland et al,
1986), the Activities of Daily Living (ADL) scale
(Katz et al, 1963),
the Instrumental Activities of Daily Living (IADL) scale
(Lawton & Brody, 1969) and
the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) interview
(Roth et al, 1986).
The interview was administered during home visits by lay interviewers who were
specially trained using video sessions and were regularly supervised.
Depression and dementia
Diagnoses of dementia and depression were made according to the GMS-AGECAT
system (Copeland et al,
1986,
1988). The Dutch-language
version has proven reliability for epidemiological work in replication studies
(Hooijer et al,
1991). Depression caseness was defined as GMS-AGECAT level 3 or
higher. A distinction is made between neurotic and psychotic depression,
indicating increasing severity levels of depression.
Socio-demographic factors
Potentially confounding covariates were age, gender and level of education.
Educational status was dichotomised into lower (primary school or less) and
higher (more than primary school) education.
Environmental vulnerability factors
Marital status was assessed based on the questions in GMS-AGECAT.
Physical health
The presence of chronic diseases was assessed with the pertinent CAMDEX
questions on cardiovascular disease, cancer, lung disease, diabetes,
Parkinson's disease, arthritis and epilepsy. Cognitive status was assessed by
MMSE score. Subjects were considered to have functional disability if their
ADL or IADL scores were two or more points below the maximum score on the
respective scales.
Mortality
The follow-up for recording deaths extended from the date of the clinical
examination until 1 July 1996. The dates of death were ascertained from the
registers of the municipality of Amsterdam, or the municipalities to which
subjects had moved during the study period. The follow-up period was 6 years,
with an average of 55.5 months (s.d. = 16.7, range 1-73 months). Data were
missing on six subjects (0.1%).
Data analysis
Baseline sample characteristics were compared between men and women using
2 statistics. Mortality rates per 1000 person-years were
calculated according to depressed mood status. Bivariate associations of
mortality at follow-up (deceased or alive on 1 July 1996) with independent
variables at baseline were assessed by calculating relative risks. When the
95% confidence interval of the latter did not include one, the association was
regarded as statistically significant.
Kaplan-Meier curves and Cox proportional hazard regression models were used to examine further the association between depression and time to mortality in men and women separately. The risk of mortality was expressed as the mortality rate ratio (RR). In multivariate analysis, the effect of depression on mortality was studied for the two types of depression (neurotic and psychotic), with successive adjustment for potential confounding factors: sociodemographic factors, environmental factors, cardiovascular and other chronic diseases, cognitive decline and functional disability. As disability may be a consequence of depression (Penninx et al, 1998) and therefore may cause over-correction for the effect of depression on mortality, this variable was entered as a last, separate step. The difference between two mortality RR values was considered to be statistically significant if the confidence intervals of either variable did not overlap with the value of the opposing variable.
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RESULTS |
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Associations of risk factors with mortality
The total follow-up time of the sample was 18 726 person-years, and 1035
(25.6%) subjects had died during the study period. The crude mortality rate
was 55.3 deaths per 1000 person-years. Bivariate analysis of baseline
characteristics with mortality showed that all risk factors, except arthritis,
were associated with mortality in both men and women
(Table 2). Of the men with
psychotic depression, 75% had died at follow-up, whereas in women this figure
was only 41.4%. The presence of neurotic depression in men
doubled the mortality from 30.3% (without depression) to 59.3%. In women the
presence of neurotic depression only slightly raised the mortality from 20.5%
to 23.1% (RR not statistically significant).
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In Kaplan-Meyer analysis, depression was found to have a significant negative effect on survival. This effect was more pronounced in men than in women. In men, both neurotic and psychotic depression were associated with higher mortality, whereas in women this was only the case for psychotic depression (Figs 1 and 2).
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Stepwise hierarchical regression using the Cox proportional hazards model, with successive adjustment for potential confounding and explanatory variables, also showed different results for men and women (Table 3). In women, the mortality risk for all depression was significantly lower than in men, and was reduced to a statistically non-significant level when adjusting for other variables. The unadjusted mortality risk for neurotic depression was not statistically significant in women (RR=1.14, 95% CI 0.90-1.45) and less than half of the associated mortality risk in men (RR=2.67, 95% CI 1.98-3.60), yielding a statistically significant difference between men and women. In men, the higher initial mortality risks for both all depression and for neurotic depression still showed a statistically significant impact of depression after adjustment for all other possible explanatory factors.
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Although the initial mortality risk for psychotic depression was considerably higher in men (RR=3.77 v. 2.43 in women), the difference was not statistically significant. Successive adjustment for other variables then reduced the mortality risk for psychotic depression in both men and women to a statistically non-significant level. However, if the last step, adjustment for functional disabilities, was not taken into account, the mortality rate ratio for psychotic depression in women remained statistically significant (RR=1.66, 95% CI 1.08-2.55), whereas in men it only just failed to reach statistical significance (RR=1.64, 95% CI 0.96-2.78). It should be noted that, especially in men, the numbers of patients with psychotic depression were rather small to perform statistical testing with a relatively large number of control variables (24 men with psychotic depression and 58 women). Finally, there were no substantial interactions between depression (all, neurotic, psychotic) and somatic or organic disorders in either men or women.
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DISCUSSION |
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Main findings
The overall prevalence of depression (12.9%) was well within the range of
what has been found in other studies of depression in community-living elderly
(Beekman et al, 1999).
The unadjusted mortality risks showed depression to be associated with
mortality, with a considerably stronger impact on survival of the more severe,
psychotic depression. This trend is consistent with earlier findings
(Penninx et al,
1999), and confirms that the more severe the depression, the
higher the associated mortality. These effects, however, were modified by
gender. Although, consistent with the literature
(Wolk & Weisman, 1995),
the total prevalence of depression was found to be 2.4 times higher in women
than in men, its negative effect on survival in women was less pronounced. A
very large proportion of men with psychotic depression (75%) had died after a
follow-up of six years, whereas in women this was clearly lower, although
still considerable (41.4%). Likewise, neurotic depression in men showed a much
higher mortality risk than in women.
After controlling for other explanatory variables, this overall impression did not change. The mortality risk of psychotic depression remained statistically significant in women, and very nearly significant in men, when the last step in subsequent adjustment was not taken into account. As functional disability has been found to be a consequence of depression, and the numbers of men with psychotic depression were rather small, it appears to be a reasonable conclusion that psychotic depression is associated with a higher mortality risk in both men and women. The gender differences were, however, most striking when investigating the more prevalent neurotic depression. Even unadjusted, neurotic depression in women was not found to be significantly associated with mortality. The mortality risk in men, however, remained statistically significant after controlling for all competing factors that may have affected survival.
Methodological considerations
A first methodological explanation for the gender differences observed may
be that there has been report bias, differentially affecting prevalence rates
of depression in men and women. One possible explanation is that women are
culturally more prone to report depressive complaints, and therefore have
higher depression scores. A de facto broader definition of depression in women
would thus conceal the real effect that more severe, clinically relevant
levels of depression may have on mortality. There are some data that support
this proposition (Angst &
Dobler-Mikola, 1984), but most studies failed to confirm it
(Wolk & Weisman, 1995).
Symptom patterns in men and women are very much alike, and studies in
different adult age groups consistently show a female preponderance in
depression (Sonnenberg et al,
2000). If the current study had taken into account only psychotic
depression, the gender distribution would have been less skewed (women have
1.4 times more psychotic depression than men, instead of 2.7 times that of men
in neurotic depression). Still, the mortality risk (RR) for psychotic
depression was almost two-fold higher in men, demonstrating a robust
difference between the effects of depression in men and women.
A second methodological explanation for the observed gender difference may be that depressed subjects are more inclined to report negatively about their own health (Raphael & Cloitre, 1994). In studies such as ours, in which every effort was made to control for confounding, report bias may lead to overcorrection in multivariate analysis. Owing to the higher prevalence of depression, this effect may be stronger in women. However, the unadjusted mortality RR values for depression are already much lower or statistically insignificant in women, suggesting that a possible control bias does not account for the difference. Report bias thus appears to be an improbable explanation for the observed gender differences.
A third source of bias may be selective non-response. A previous study in this sample by Launer et al (1994) revealed that non-responders to the baseline assessment more often reported a heart attack, stroke and diabetes, and were more likely to be unmarried, to have a lower education, to do poorly on cognitive tests and to have a history of psychiatric illness. There were no differences in response rate between men and women (OR=1.0, 95% CI 0.6-1.5). We therefore conclude that only the very ill and cognitively impaired may have been underrepresented in the current study. This appears similar to the non-response pattern found in other community studies. Risk factors for mortality, however, were well represented in men and women throughout the age strata of the study population. Owing to the efficient functioning of Dutch community registers, measurement of the outcome variable of this study was 99.9% complete. Thus, the results do not appear to be fundamentally affected by this non-response pattern.
The conclusion is therefore justified that depression is associated with a higher mortality in older men than in older women. This is especially true for depression syndromes generally considered to be milder that do not meet the criteria for major depressive disorder. Our findings offer an explanation for some of the contradictory findings of earlier studies on pervasive or minor depression and mortality, most of which did not specifically address gender as an effect modifier.
Implications
Both the theoretical and clinical implications of this finding are
considerable. Earlier research has shown that depressive symptoms are of major
importance to physical, social and role functioning
(Beekman et al, 1997).
After controlling for the effects of a variety of serious somatic conditions
our data show that depression also exerts an influene on mortality in men.
Even though there is a growing consensus on the fact that mild or
sub-threshold depressive syndromes (not meeting full diagnostic
criteria for DSM-IV (American Psychiatric
Association, 1994) or ICD-10
(World Health Organization,
1993)) identified by screening methods such as GMS-AGECAT deserve
clinical attention (Pincus et al,
1999), recognition is poor
(German et al, 1987).
The majority of depressed patients living in the community do not receive any
specific treatment for their depressive complaints. Treatment studies,
however, confirm the gender-specific pattern and suggest that the potential
effect of depression on mortality can be affected by treatment. Avery &
Winokur (1976) showed that
treatment of clinically admitted patients with major depression significantly
reduced the number of deaths through myocardial infarctions. They found the
impact of adequate treatment of depression to be especially influential on the
survival of older men. A study by Craig & Lin
(1981), comparing pre-drug era
and post-drug era patient samples, revealed that the decline in mortality
associated with the introduction of psychiatric drug treatment was also
especially marked in elderly men.
Possible explanations for the observed gender differences
Although it has long been pointed out that untreated depressed subjects
tend to be in worse health due to continuous agitation, malnourishment,
intercurrent infections and cardiovascular problems
(Malzberg, 1937), and are also
more likely to die from accidents or suicide
(Tsuang & Woolson, 1978),
a clear explanation for the gender-specific pattern has not been provided.
A possible explanation may be that men have more cardiovascular pathology, the course of which is affected more strongly by comorbid depression. A number of studies have shown depression to be related to a less favourable course of cardiovascular disease (Avery & Winokur, 1976; Frasure-Smith et al, 1995). These studies, however, investigated the impact of major depression and not of less severe depressive syndromes.
A tentative psychological explanation for the excess mortality in men may be that men are less equipped to deal with feelings of hopelessness and depression than women. Women are more inclined to discuss such feelings with others (Briscoe, 1982), are more open to accepting support from others when experiencing them (Longino & Lipman, 1981) and therefore are more able to sustain and overcome feelings of depression (Grootheest et al, 1999). The male coping style is more externalising, and feelings of depression will only be experienced by men when other, more typical forms of coping have not been successful. A depressive syndrome in men thus signifies a more invalidating and threatening condition than such a syndrome in women, which is reflected in the robust differences in mortality.
A third, possibly related, mechanism explaining the gender differences we found may be that depressed elderly men are more inclined to commit suicide than depressed women (Conwell et al, 1996).
As the current data do not include the causes of death, the question on the exact mechanism cannot be addressed directly. However, the finding of a relation between milder depression and mortality, especially in elderly men, is robust in this study. For a clinician to focus solely on patients with DSM-IV major depressive disorder, a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration, appears once more to be an underestimation of the actual level of morbidity. Although the majority of the community-dwelling elderly with depressive syndromes who were investigated in this study had not been treated for depression, earlier data suggest that they might have derived important benefits from it. With an average total prevalence of 13.5% (Beekman et al, 1999), later-life depressive syndromes are likely to be found in all medical settings and may affect the course of a variety of conditions. This study lends a strong basis to the notion that, together with patients suffering from more severe levels of depression, elderly men with neurotic or minor depression deserve to be recognised and treated more vigorously than is currently practised.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication December 6, 1999. Revision received April 25, 2000. Accepted for publication April 27, 2000.