Mortality associated with depression: a forty-year perspective from the Stirling County Study.

BACKGROUND: This report concerns long-term mortality risks associated with depression, and the potentially confounding factors of alcoholism and cigarette smoking, as experienced by a general population assessed at a baseline in 1952, followed for re-assessment of survivors in 1968, and for death by 1992. METHODS: Self-report and physician-report information was gathered in 1952 and again in 1968 about a sample of 1,079 adults. At the end of follow-up in 1992, the vital status of all subjects was known. Comorbidity among depression, alcoholism, and smoking was investigated. Cox regression models were employed to estimate hazard ratios (HRs) as indicators of mortality risk. Models including age, gender, and depression were fit for the complete sample at baseline as well as for re-assessed survivors. Models simultaneously controlling for the mortality risks associated with depression, alcoholism, and heavy smoking were fit for men. RESULTS: At the baseline in 1952, depression was somewhat more common among women than men (4% compared to 6%) but was found to carry a significant mortality risk only among men (HR 2.7, 95% CI 1.6-4.7). Based on re-assessments made in 1968, depression was associated with mortality risk among both men (HR 2.2, 95% CI 1.0-4.5) and women (HR 2.1, 95% CI 1.2-3.8). In 1952, more than 20% of men smoked cigarettes excessively and 8% abused alcohol, but very few of these groups of men were also depressed. In the original sample and also among the survivors, depression, alcoholism, and heavy smoking were separately associated with mortality among men. Depression and alcoholism carried a more immediate mortality risk while heavy smoking a more delayed one. CONCLUSIONS: At the baseline of the Stirling County Study, the mortality risk associated with depression among men was not enhanced or explained by abuse of alcohol or nicotine, mainly because comorbidity was rare at that time. The longitudinal research of the study has pointed to a number of psychiatrically-relevant time-trends such as the fact that an association between depression and cigarette smoking did not appear until the 1990s. It is hypothesized that a similar trend may emerge over time regarding the comorbidity of depression and alcoholism. A trend reported here was that, while depressed women in the original sample did not carry a significant mortality risk, the surviving women who were depressed at the time of re-assessment exhibited a mortality risk that was as significant as that for men. Such information may provide a useful back-drop for future investigations.

Cell type specificity of lung cancer associated with arsenic ingestion.

Arsenic is a well-documented human carcinogen. Previous studies on urinary bladder and skin cancers have shown that arsenic can cause specific cell types of malignancy. To evaluate whether this is also true for lung cancers, we conducted a study on 243 townships in Taiwan. We identified patients through the National Cancer Registry Program and compared the proportion of each major cell type between an endemic area of arsenic intoxication with exposures through drinking water, which includes 5 of the townships and the other 238 townships. To control for gender and age, we analyzed data on men and women separately and divided patients into four age groups. A total of 37,290 lung cancer patients, including 26,850 men and 10,440 women, was diagnosed between January 1, 1980 and December 31, 1999 in study townships. Patients from the endemic area had higher proportions of squamous cell and small cell carcinomas, but a lower proportion of adenocarcinomas. These findings were similar across all age groups in both genders, although the lack of data on smoking is a limitation of our study. The results suggested that the carcinogenicity of arsenic on lungs is also cell type-specific: squamous cell and small cell carcinomas appeared to be related to arsenic ingestion, but not adenocarcinoma. Whereas data in the literature are limited, the association between adenocarcinoma and arsenic exposures through inhalation appeared to be stronger than that of squamous cell carcinoma. Therefore, we speculate that arsenic may give rise to different mechanisms in the development of lung cancers through different exposure routes.

Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast.

Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P < 0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks.

Cigarette smoking in relation to depression: historical trends from the Stirling County Study.

OBJECTIVE: Building on findings about the prevalence and incidence of depression over a 40-year period, the authors provide data on trends in cigarette smoking and associations with depression. METHOD: Data come from interviews with adult population samples (1952, 1970, and 1992) and followed cohorts (1952-1970 and 1970-1992). Logistic regression models and survival regressions were used to analyze the data. RESULTS: The associations between smoking and depression were small and nonsignificant in 1952 and 1970. In 1992, however, the odds that a smoker would be depressed were three times the odds that a nonsmoker would be depressed. The interaction between smoking and study year was significant, indicating that the association was limited to the most recent sample. In the cohort analysis, smoking at baseline did not predict the onset of depression, but subjects who became depressed were more likely to start or continue smoking and less likely to quit than those who never had a depression. CONCLUSIONS: In terms of population trends, the association between depression and cigarette smoking became prominent as the use of tobacco declined because of awareness of the risks involved. The findings about individuals followed over time suggest that those who became depressed were more involved with nicotine than those who never had a depression. The authors discuss hypotheses involving "self-medication," risk-taking, and changes in the social climate but conclude that the relationships between smoking and depression are probably multiple and complex.