Background
The association between depression and mortality in older community-dwelling populations is still unresolved. This study determined the effect of both minor and major depression on mortality and examined the role of confounding and explanatory variables on this relationship.
Methods
A cohort of 3056 men and women from the Netherlands aged 55 to 85 years were followed up for 4 years. Major depression was defined according to DSM-III criteria by means of the Diagnostic Interview Schedule. Minor depression was defined as clinically relevant depression (defined by a Center for Epidemiologic Studies Depression score ≥16) not fulfilling diagnostic criteria for major depression.
Results
After adjustment for confounding variables (sociodemographics, health status), men with minor depression had a 1.80-fold higher risk of death (95% confidence interval, 1.35-2.39) during follow-up than nondepressed men. In women, minor depression did not significantly increase the mortality risk. Irrespective of sex, major depression was associated with a 1.83-fold higher mortality risk (95% confidence interval, 1.09-3.10) after adjustment for sociodemographics and health status. Health behaviors such as smoking and physical inactivity explained only a small part of the excess mortality risk associated with depression.
Conclusion
Even after adjustment for sociodemographics, health status, and health behaviors, minor depression in older men and major depression in both older men and women increase the risk of dying.
MORTALITY studies in psychiatry are important because they are an integral part of the effort to develop a comprehensive understanding of the development, course, and outcome of psychiatric disorders.1 Previous mortality studies have concentrated either on major depression, as defined by DSM-IV criteria,2 or on depressive symptoms in general, not specifically defining the type of depression. The latter mainly include cases of marked depressive symptoms below the severity threshold of major depression, often referred to as subthreshold or minor depression.3,4
The few community-based studies on major depression have described an increased mortality risk.5-8 However, for minor depression, both the presence9-11 and the absence12-16 of an excess mortality risk have been described. Three studies found an increased mortality risk in depressed men but not in depressed women.7,10,17
Disparate findings regarding the effect of depression on mortality might partly be explained by failure to control for the effects of health status and socioeconomic status in some studies.12 Since depressed persons usually have a lower socioeconomic status and a worse health status than their nondepressed peers,18,19 these characteristics may partly be responsible for their increased mortality risk. To what extent a possibly increased mortality risk among depressed persons is caused by confounding by socioeconomic status and health status has not been extensively described. In addition, not many attempts have been made to understand the increased risk of dying among depressed persons. Depressed persons are known to be more likely than nondepressed persons to engage in smoking, excessive alcohol intake, physical inactivity, and unhealthy eating habits.20,21 Whether these health behaviors explain part of their increased mortality risk has not been examined before, to our knowledge.
This community-based study examines the effects of both minor and major depression on mortality among older persons and explores the impact of potential confounding variables (sociodemographics, health status) and explanatory variables (health behaviors) in these effects.
Data for this study were collected in the Longitudinal Aging Study Amsterdam, a longitudinal study among persons aged 55 to 85 years. Data collection procedures and nonresponse have been described in depth.22 In short, a random sample was drawn from the population registries of 11 municipalities in 3 geographic areas in the Netherlands. The sample was stratified by sex and age according to expected mortality at midterm of the Longitudinal Aging Study Amsterdam (after 5 years) to guarantee sufficient sample sizes for longitudinal analyses within age and sex strata. The cohort was originally recruited for the study Living Arrangements and Social Networks of Older Adults (N=3805; response rate, 62.3%). Nonresponse was higher (P<.001) among the oldest old persons because of physical or cognitive impairment.23 After 10 months, between September 1992 and September 1993, the Living Arrangements and Social Networks of Older Adults Study participants were approached again for the face-to-face Longitudinal Aging Study Amsterdam interview. A total of 3107 (81.7%) took part; 126 (3.3%) had died before approach; 44 (1.2%) could not be contacted; 134 (3.5%) were too ill or cognitively impaired to be interviewed; and 394 (10.4%) were unwilling to participate because of lack of interest. For the present study, 51 (1.6%) of the 3107 subjects were unavailable for subsequent analyses because of missing depression data, leaving a study sample of 3056.
The Center for Epidemiologic Studies Depression Scale (CES-D)24 was used to measure depressive symptoms experienced during the previous week. This 20-item self-report scale, ranging from 0 to 60, has proved to be a valid and reliable instrument in older populations.25 In our study, the internal reliability was high (Cronbach α=.87). The commonly used CES-D cutoff score of 16 was used to identify persons with a high level of depression. All subjects scoring above this cutoff were approached for a diagnostic interview, which was included in a second interview a few weeks after baseline (response rate, 86.0% relative to baseline). Nonresponse for the second interview was significantly higher among persons with higher age and more chronic diseases (P<.001), but was not related to sex. With the use of the Diagnostic Interview Schedule,26 major depression (6-month recency) was defined according to DSM-III criteria.27 Since a random sample of 330 screened negatives (CES-D score <16) also underwent a Diagnostic Interview Schedule interview, the criterion validity of the CES-D for major depression could be determined and appeared to be excellent (sensitivity, 100%; specificity, 88%).25 The definition of minor depression was not exactly based on research diagnostic DSM-IV criteria (developed after the start of our study) but was in line with Angst and Merikangas' definition of subthreshold depression.28 Subthreshold depression identifies persons with clinically relevant depressive syndrome (CES-D score ≥16) below the diagnostic severity threshold for major depressive disorder. In our study, 9.1% of the persons with minor depression fulfilled DSM-III criteria for dysthymia, and 62.3% still had a minor depression during a follow-up measurement after 5 months, illustrating the chronic nature of minor depression. In another study, it was shown that 43% of those with baseline minor depression were depressed during all 5 measurements during 1 year.29 As expected, persons with major depression had a higher mean CES-D score (25.9) than those with minor depression (22.3) (P=.01), which confirms more severe depressive symptoms in major depression. Persons with a CES-D score of 16 or more and missing Diagnostic Interview Schedule data (18.7% of those with a CES-D score ≥16) were categorized as having minor depression. Some of these persons might have been misclassified because they could have had major depression. To check the effect of missing Diagnostic Interview Schedule data, all analyses were repeated after excluding persons with missing second-interview data.
Death certificates were traced through the registries of the municipalities in which the respondents were registered. Vital status ascertainment was 100% complete. All deaths that occurred between the baseline interview and October 1, 1997, were recorded. The follow-up period lasted, on average, 50 months (4.2 years), ranging from 1 to 60 months. Information about causes of death was obtained through the Dutch Central Bureau of Statistics and coded according to the International Classification of Diseases, Ninth Revision. The following causes of death were distinguished (International Classification of Diseases, Ninth Revision,30 codes in parentheses): cardiovascular disease (401-429, 440-459), stroke (430-438), diabetes (250), gastrointestinal tract disease (530-579), cancer (140-208), respiratory disease (460-519), accidents (E800-E929), suicide (E950-E959), and other causes (remaining codes).
Potentially confounding covariates were sociodemographics and health status at baseline. Sociodemographics included age, sex, education, and level of urbanization. Chronic disease status was assessed by self-reports of heart disease, peripheral atherosclerosis, stroke, diabetes mellitus, lung disease, cancer, and arthritis. Physical disability in daily life was assessed by a 3-item questionnaire31 and classified as none, moderate (1 disability), and severe (≥2 disabilities). Disability can be considered a rough indicator of illness severity and, consequently, is a potential confounder of the association between depression and mortality. However, since depression in itself also results in subsequent physical decline and disability,32-37 disability may also be part of the explanatory mechanism by which depression links to mortality. Consequently, the consideration of disability as a pure confounder would result in an overadjusted estimate of the mortality risk of depression. In this study, disability is considered a potential confounder as well as a potential explanatory variable.
Other potentially explanatory variables included health behaviors such as smoking (none, former smoker, or current smoker), excessive alcohol consumption (an average of 3 drinks or more per day), and body mass index (BMI) (computed as weight in kilograms divided by the square of height in meters). Physical activity was assessed by asking respondents whether they had engaged in walking, bicycling, light and heavy household activities, gardening, and sports activities in the previous 2 weeks. Based on the total number of activities reported, physical activity was classified as low (0-2 activities), moderate (3-4 activities), or high (5-6 activities).
Respondents were divided into 3 depression categories: no depression, minor depression, and major depression. Study characteristics across these groups were compared by means of χ2 statistics. Mortality rates per 1000 person-years were calculated according to depression status. Overall estimates of the relative risk of death were computed from Cox proportional hazards regression models. In multivariate models, the effect of depression on mortality was studied after successive adjustment for potential confounders (sociodemographics, chronic diseases) and potential explanatory variables (health behaviors). To rule out possible interaction between depression and covariates in predicting mortality, the significance of product terms between depression and covariates was tested.
Mean age of the 3056 respondents was 70.6 years, and 51.6% were female. Of the respondents, 2603 (85.2%) were not depressed, 392 (12.8%) had a minor depression, and 61 (2.0%) had a major depression. As compared with the nondepressed, subjects with minor depression were significantly older; more often female; less educated; more often living in urbanized areas; more diseased, physically disabled, and physically inactive; and more often current smokers (P<.01) (Table 1). Most of these characteristics were also found, although to a lesser extent, for major depression. However, a striking difference emerged for age: persons with major depression were significantly younger than those with minor depression.
In total, 561 subjects (18.4%) died during the follow-up of, on average, 50 months. In univariate analysis, significant predictors (P<.01) of mortality were advanced age (P<.001), male sex (P<.001), low level of education (P<.001), high urbanization level (P=.002), presence of all specific chronic diseases except arthritis (P<.001), physical disability (P<.001), current smoking (P=.02), low or high BMI (P=.04 and P=.003, respectively), and physical inactivity (P<.001). The crude mortality rate per 1000 person-years was 39.5 for the nondepressed, 71.4 for persons with minor depression, and 60.7 for those with major depression (Table 2). Persons with minor depression had a significant 1.84-fold higher risk of dying than nondepressed persons (95% confidence interval [CI], 1.49-2.27). This risk was reduced somewhat after adjustment for sex and age (relative risk [RR], 1.65; 95% CI, 1.33-2.04). However, the age-adjusted mortality risk of minor depression was much higher in men (RR, 2.02; 95% CI, 1.53-2.67) than in women (RR, 1.27; 95% CI, 0.92-1.76) (Figure 1). The significance of this interaction by sex was tested by adding the sex×minor depression interaction term in the age- and sex-adjusted model. Since the interaction term was statistically significant (P=.05), the remainder of the findings for minor depression will be presented for men and women separately. For major depression, the unadjusted mortality risk was 1.55 (95% CI, 0.92-2.58). Adjustment for sex and age increased the mortality risk to 2.32 (95% CI, 1.38-3.89) (Figure 1). No interaction by sex was present for major depression (P of interaction term, .53).
In men, adjustment for age, education and urbanization, and chronic diseases reduced the mortality risk of minor depression to 1.80 (Table 3). Adjustment for physical disability further reduced the mortality risk considerably, but minor depression remained significantly associated with mortality (1.57). Adjustment for BMI, smoking, and physical activity reduced the mortality risk to 1.45 (95% CI, 1.08-1.95). In women, minor depression was not significantly associated with mortality after adjustment for age (Table 3) and became even smaller than 1.0 after further adjustment for confounders and explanatory variables.
After adjustment for sociodemographics and chronic diseases, persons with major depression had a 1.83-fold higher risk of dying than those who were not depressed (Table 3). Adjustment for physical disability, BMI, smoking, and physical activity reduced the mortality risk for major depression, but the risk was still significantly increased (RR, 1.68; 95% CI, 1.00-2.84).
The increased mortality risks for major and minor depression were not caused by suicide. Only 3 persons committed suicide: 1 woman with minor depression and 1 man and 1 woman without depression at baseline (Table 4). A large proportion (46.7%) of the persons with major depression died because of cardiovascular disease, but, probably because of small numbers, this was not signficantly different from the proportions in nondepressed persons (31.1%) and those with minor depression (29.4%). Nondepressed persons had significantly more cancer mortality, whereas persons with minor depression died somewhat more often because of respiratory disease.
The minor depression category included 73 persons who scored above the CES-D cutoff but did not participate in the second interview. Consequently, these persons could have had major depression instead of minor depression. To check the effect of this potential misclassification, analyses were repeated after excluding those with missing second-interview data. These analyses yielded similar results for minor depression: the mortality risk adjusted for chronic diseases and sociodemographics was 1.97 (95% CI, 1.42-2.72) in men and 1.09 (95% CI, 0.74-1.61) in women.
As expected, anxiety disorders (defined by DSM-III criteria) were more prevalent among the depressed.38 However, anxiety disorders were not significantly associated with mortality (adjusted risk, 1.04; 95% CI, 0.59-1.82), and adjustment for anxiety disorders did not influence the mortality risks for depression. In addition, we checked whether the results for minor depression could be caused by the 6 somatic items of the CES-D scale. After these items were deleted, minor depression (defined by a score ≥11 using the remaining 14 CES-D items) was even slightly more predictive of mortality in men (for sociodemographics and diseases, adjusted RR, 2.05; 95% CI, 1.53-2.74) and not in women (adjusted RR, 0.95; 95% CI, 0.66-1.37). Finally, to rule out possible interaction by sociodemographics or health status, product terms between depression and covariates were entered in the regression models. No interactions were found; effects of major and minor depression were similar across strata of age, education, urbanization, and disease status.
The present study provides evidence that minor depression among older men and major depression among older men and women increase the risk of dying during 50 months of follow-up. Major depression was defined according to diagnostic DSM-III criteria, whereas minor depression was defined as subthreshold depression including syndromes such as dysphoria, dysthymia, and adjustment disorder. The mortality risks were statistically significant after adjustment for sociodemographics and health status. A small part of the mortality risk of depression was caused by health behaviors, mainly smoking and physical inactivity, which are more common in depressed than in nondepressed older persons. However, even after adjustment for these health behaviors, the detrimental effects of major depression (in general) and minor depression (in men only) remained significantly present.
In line with our findings, an increased mortality risk for major depression has been found consistently.5-8 Minor depression was associated with mortality in some studies9-11 but not in others.12-16 These disparate findings may result from the different age ranges in earlier mortality studies. Gallo et al35 suggested that minor depression may be expressed differently in the elderly, with more emphasis on hopelessness and despair and less on sadness. Consequently, our findings for minor depression may be specific to the older population. Another explanation for previous disparate findings is that many mortality studies did not differentiate the effects between men and women. In line with other studies,7,10,17 our findings show that an increased mortality risk for minor depression was found in men but not in women. There might be some reasons for such a sex difference. First, women's physiological and behavioral reactions to stress may differ from those of men.39 Second, men more often die because of cardiovascular disease than women do. Other study results17,40 suggest that depression is a stronger risk factor for cardiovascular death than for other causes of death. Our findings support this suggestion for major depression but not for minor depression. Third, women and men may psychologically define events differently. Since major depression is defined by more rigorous clinical criteria, a sex difference in its conceptualization is less likely. However, for minor depression, Angst and Dobler-Mikola41 found that men reported fewer depressive symptoms than women at the same degree of impairment of psychosocial functioning, thereby possibly causing an artifactual female preponderance. Also, effects of life events and changing social networks on minor depression were found to be greater in older women than in older men.42,43 For men, it has been suggested that minor depression partly represents a premonitory sign of subclinical disease.17 Differing minor depression concepts in older women and men44 might be responsible for the sex-differential effect of minor depression.
Our findings provide insight into the role of confounders and explanatory variables in the effect of depression on mortality. Adjustment for the fact that persons with minor depression are older, less educated, and more diseased and more often live in urbanized areas than nondepressed persons reduced the excess mortality risk for minor depression considerably. Persons with major depression, however, were younger and more often female than the nondepressed, which caused an increase in the mortality risk for major depression after adjustment for sociodemographics and health status. In addition, differences in health behavior between depressed (both major and minor) and nondepressed persons explained part of the excess mortality risk. Depressed persons were found to be substantially less physically active, were more often smokers, and more often had a lower BMI, which might partly reflect lack of appetite. Adjustment for these factors further decreased the mortality risk for depression.
Even after adjustment for health behaviors, minor depression in men and major depression in both men and women significantly increased the risk of dying. Therefore, other explanations should be considered as well. First, as shown in clinical populations, a direct consequence of (major) depression is suicide. However, as in other community-dwelling older samples,8,17,45 suicide was rare in our study (only 3 cases) and did not explain the increased mortality risks for depression. Second, it has been hypothesized that depressed persons are less likely to comply with treatment recommendations,46 which could have unfavorable health consequences. Third, depression itself may cause physiological changes that enhance susceptibility to disease and, consequently, lead to death. Depression has been found to adversely affect endocrine, neurologic, and immune processes by increasing the sympathetic tone, decreasing vagal tone, and causing immunosuppression.47-49 Alternative explanations are that depression represents a reaction to subclinical disease that places subjects at greater risk for mortality, or that a third factor, related to both, causes the depression and mortality link.
The identification of major depression and minor depression as risk factors for mortality in old age is important. Earlier studies have shown that major and minor depression have a large range of unfavorable consequences: they affect well-being, physical function, morbidity, and utilization of services.32-36,50-53 Our study adds mortality to this list and supports that the adverse health consequences of depression are very diverse. Depression is a potentially modifiable condition, but, unfortunately, it is often unrecognized and untreated in older persons.54 The results of this study support ongoing efforts to achieve a more active policy regarding major as well as minor depression in late life.
Accepted for publication June 29, 1999.
This study was based on data collected in the context of the Longitudinal Aging Study Amsterdam, which is largely funded by the Netherlands Ministry of Welfare, Health and Sports, The Hague, the Netherlands. The work of Dr Penninx was supported by a grant of the Dutch Organization of Scientific Research, The Hague.
Corresponding author: Brenda W. J. H. Penninx, PhD, EMGO Institute, Vrije Universiteit, vd Boechorststraat 7, 1081 BT Amsterdam, the Netherlands (e-mail: BWJH.Penninx.EMGO@med.vu.nl).
1.Tsuang
MTSimpson
JC Mortality studies in psychiatry: should they stop or proceed?
Arch Gen Psychiatry. 1985;4298- 103
Google ScholarCrossref 2.American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC American Psychiatric Association1994;
3.Blazer
DG Epidemiology of late-life depression. Schneider
LJReynolds
CHLebowitz
BDFriedhoff
AJeds.
Diagnosis and Treatment of Late Life Depression: Results of the NIH Consensus Development Conference. Washington, DC American Psychiatric Association1994;9- 21
Google Scholar 4.Tannook
CKatona
K Minor depression in the aged: concepts, prevalence and optimal management.
Drugs Aging. 1995;6278- 292
Google ScholarCrossref 5.Bruce
MLLeaf
PJ Psychiatric disorders and 15-month mortality in a community sample of older adults.
Am J Public Health. 1989;79727- 730
Google ScholarCrossref 6.Pulska
TPahkala
KLaippala
PKivelá
S-L Major depression as a predictor of premature deaths in elderly people in Finland: a community study.
Acta Psychiatr Scand. 1998;97408- 411
Google ScholarCrossref 7.Zheng
DMacera
CACroft
JBGiles
WHDavis
DScott
WK Major depression and all-cause mortality among white adults in the United States.
Ann Epidemiol. 1997;7213- 218
Google ScholarCrossref 8.Zubenko
GSMulsant
BHSweet
RAPasternak
REMing Tu
X Mortality of elderly patients with psychiatric disorders.
Am J Psychiatry. 1997;1541360- 1368
Google Scholar 9.Barefoot
JCSchroll
M Symptoms of depression, acute myocardial infarction, and total mortality in a community sample.
Circulation. 1996;931976- 1980
Google ScholarCrossref 10.Murphy
JMMonson
RROlievier
DCSobol
AMLeighton
AH Affective disorders and mortality: a general population study.
Arch Gen Psychiatry. 1987;44473- 480
Google ScholarCrossref 11.Enzell
K Mortality among persons with depressive symptoms and among responders and non-responders in a health check-up.
Acta Psychiatr Scand. 1984;6989- 102
Google ScholarCrossref 12.Roberts
REKaplan
GACamacho
TC Psychological distress and mortality: evidence from the Alameda County Study.
Soc Sci Med. 1990;31527- 536
Google ScholarCrossref 13.Thomas
CKelman
HRKennedy
GJAhn
CYang
C Depressive symptoms and mortality in elderly persons.
J Gerontol. 1992;47S80- S87
Google ScholarCrossref 14.Vogt
TPope
CMullooly
JHollis
J Mental health status as a predictor of morbidity and mortality: a 15-year follow-up of members of a health maintenance organization.
Am J Public Health. 1994;84227- 231
Google ScholarCrossref 15.Fredman
LSchoenbach
VKaplan
BHBlazer
DGJames
SAKleinbaum
DGYankaskas
B The association between depressive symptoms and mortality among older participants in the Epidemiologic Catchment Area–Piedmont Health Survey.
J Gerontol Soc Sci. 1989;44149- 156
Google ScholarCrossref 16.Wassertheil-Smoller
SApplegate
WBBerge
KChange
CJDavis
BRGrimm
R
JrKostis
JPressel
SSchron
Efor the SHEP Cooperative Research Group, Change in depression as a precursor of cardiovascular events.
Arch Intern Med. 1996;156553- 561
Google ScholarCrossref 17.Penninx
BWJHGuralnik
JMMendes de Leon
CFPahor
MVisser
MCorti
MCWallace
RB Cardiovascular events and mortality in newly and chronically depressed persons >70 years of age.
Am J Cardiol. 1998;81988- 994
Google ScholarCrossref 18.Beekman
ATFDeeg
DJHvan Tilburg
TSmit
JHHooijer
Cvan Tilburg
W Major and minor depression in later life: a study of prevalence and risk factors.
J Affect Disord. 1995;3665- 75
Google ScholarCrossref 19.Kennedy
GJKelman
HRThomas
CWisniewski
WMetz
HBijur
PE Hierarchy of characteristics associated with depressive symptoms in an urban elderly sample.
Am J Psychiatry. 1989;146220- 225
Google Scholar 20.Aneshensel
CHuba
G Depression, alcohol use, and smoking over one year: a four-wave longitudinal causal model.
J Abnorm Psychol. 1983;921134- 1150
Google Scholar 21.Stephens
T Physical activity and mental health in the United States and Canada: evidence from four population surveys.
Prev Med. 1988;1735- 47
Google ScholarCrossref 22.Deeg
DJHKnipscheer
CPMvan Tilburg
W Autonomy and Well-being in the Aging Population: Concepts and Design of the Longitudinal Aging Study Amsterdam. Bunnik, the Netherlands Netherlands Institute of Gerontology1994;NIG Trend Studies No. 7.
23.Broese van Groenou
MIvan Tilburg
TGde Leeuw
EDLeitbroer
AC Data collection. Knipscheer
CPMde Jong Gierveld
Jvan Tilburg
TGDykstra
PAeds.
Living Arrangements and Social Networks of Older Adults in the Netherlands: First Results. Amsterdam, the Netherlands VU University Press1995;185- 197
Google Scholar 24.Radloff
LS The CES-D scale: a self-report depression scale for research in the general population.
Appl Psychol Meas. 1977;1385- 401
Google ScholarCrossref 25.Beekman
ATFDeeg
DJHvan Limbeek
JBraam
AWde Vries
MZvan Tilburg
W Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community based sample of older adults in the Netherlands.
Psychol Med. 1997;27231- 235
Google ScholarCrossref 26.Robins
LNHelzer
JECroughan
JRadcliff
KS National Institute of Mental Health Diagnostic Interview Schedule: its history, characteristics, and validity.
Arch Gen Psychiatry. 1981;38381- 389
Google ScholarCrossref 27.American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Washington, DC American Psychiatric Association1987;
28.Angst
JMerikangas
K The depressive spectrum: diagnostic classification and course.
J Affect Disord. 1997;4531- 39
Google ScholarCrossref 29.Beekman
ATFDeeg
DJHSmit
JHvan Tilburg
W Predicting the course of depression in the older population: results from a community based study in the Netherlands.
J Affect Disord. 1995;3441- 49
Google ScholarCrossref 30.World Health Organization, International Classification of Diseases, Ninth Revision (ICD-9). Geneva, Switzerland World Health Organization1977;
31.Kriegsman
DMWDeeg
DJHvan Eijk
JTMPenninx
BWJHBoeke
AJP Do disease specific characteristics add to the explanation of mobility limitations in patients with different chronic diseases? a study in the Netherlands.
J Epidemiol Community Health. 1997;51676- 685
Google ScholarCrossref 32.Penninx
BWJHGuralnik
JMFerrucci
LSimonsick
EMDeeg
DJHWallace
RB Depressive symptoms and physical decline in community-dwelling older persons.
JAMA. 1998;2791720- 1726
Google ScholarCrossref 33.Von Korff
MOrmel
JKaton
WLin
EHB Disability and depression among high utilizers of health care: a longitudinal analysis.
Arch Gen Psychiatry. 1992;4991- 100
Google ScholarCrossref 34.Bruce
MLSeeman
TEMerrill
SSBlazer
DG The impact of depressive symptomatology on physical disability: MacArthur Studies of Successful Aging.
Am J Public Health. 1994;841796- 1799
Google ScholarCrossref 35.Gallo
JJRabins
PVLyketsos
CGTien
AYAnthony
JC Depression without sadness: functional outcomes of nondysphoric depression in later life.
J Am Geriatr Soc. 1997;45570- 578
Google Scholar 36.Kouzis
ACEaton
WW Psychopathology and the development of disability.
Soc Psychiatry Psychiatr Epidemiol. 1997;32379- 386
Google Scholar 37.Wells
KBStewart
SHays
RDBurnam
MARogers
WDaniels
MBerry
SGreenfield
SWare
J The functioning and well-being of depressed patients: results from the Medical Outcomes Study.
JAMA. 1989;262914- 919
Google ScholarCrossref 38.Van Balkom
AJLMBeekman
ATFde Beurs
EDeeg
DJHvan Dyck
Rvan Tilburg
W Comorbidity of anxiety disorders in the community-based sample of elderly in the Netherlands.
Acta Psychiatr Scand. In press.
Google Scholar 39.Stoney
CMMatthews
KAMcDonald
RHJohnson
CS Sex differences in lipid, lipoprotein, cardiovascular, and neuroendocrine responses to acute stress.
Psychophysiology. 1988;25645- 656
Google ScholarCrossref 40.Frasure-Smith
NLesperance
FTalaijc
M Depression and 18-month prognosis after myocardial infarction.
Circulation. 1995;91999- 1005
Google ScholarCrossref 41.Angst
JDobler-Mikola
A Do the diagnostic criteria determine the sex ratio in depression?
J Affect Disord. 1984;7189- 198
Google ScholarCrossref 42.Krause
N Stress and sex differences in depressive symptoms among older adults.
J Gerontol. 1986;41727- 731
Google ScholarCrossref 43.Husaini
BAMoore
STCastor
RSNeser
WWhitten-Stovall
RLinn
JGGriffin
D Social density, stressors, and depression: gender differences among the black elderly.
J Gerontol. 1991;46236- 242
Google ScholarCrossref 44.Weissman
MMKlerman
GL Sex differences and the epidemiology of depression.
Arch Gen Psychiatry. 1977;3498- 111
Google ScholarCrossref 45.Lindesay
J Nonsuicidal mortality in late-life depression.
Int J Geriatr Psychiatry. 1989;2253- 65
Google Scholar 46.Katon
WSullivan
MD Depression and chronic medical illness.
J Clin Psychiatry. 1990;51(6 suppl)3- 11
Google Scholar 47.Ader
RCohen
NFelten
D Psychoneuroimmunology: interactions between the nervous system and the immune system.
Lancet. 1995;34599- 103
Google ScholarCrossref 48.Musselman
DLNemeroff
CB Depression and endocrine disorders: focus on the thyroid and adrenal system.
Br J Psychiatry. 1996;30(suppl 1)123- 126
Google Scholar 49.Stein
MMiller
AHTrestman
RL Depression, the immune system, and health and illness: findings in search of meaning.
Arch Gen Psychiatry. 1991;48171- 177
Google ScholarCrossref 50.Pratt
LAFord
DECrum
RMArmenian
HKGallo
JJEaton
WW Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up.
Circulation. 1996;943123- 3129
Google ScholarCrossref 51.Broadhead
WEBlazer
DGGeorge
LKTse
CK Depression, disability days, and days lost from work in a prospective epidemiologic survey: a 4-year prospective study.
JAMA. 1990;2642524- 2528
Google ScholarCrossref 52.Unützer
JPatrick
DLSimon
GGrembowski
DWalker
ERutter
CKaton
W Depressive symptoms and the cost of health services in HMO patients aged 65 years and older.
JAMA. 1997;2771618- 1623
Google ScholarCrossref 53.Beekman
ATFDeeg
DJHBraam
AWSmit
JHvan Tilburg
W Consequences of major and minor depression in later life: a study of disability, well-being and service utilization.
Psychol Med. 1997;271397- 1409
Google ScholarCrossref 54.Ormel
JKoeter
MWJvan den Brink
Wvan de Willige
G Recognition, management, and course of anxiety and depression in general practice.
Arch Gen Psychiatry. 1991;48700- 706
Google ScholarCrossref