Type A behavior and cancer mortality. Theoretical considerations and preliminary data.

If stress and cancer are related by coping failure, that connection presumably involves the immune system. This involvement has already been shown in animals. It can be hypothesized that Type A personalities (driving, impatient, sometimes hostile) go through states of repeated frustration because of unachieved goals. From that point of view, Type A individuals are alternately able to cope and unable to cope. Such a pattern would theoretically tend toward repeated episodes of suppression and recovery of the immune system, with increased probability of growth of transformed cells. An opposing hypothesis, derived from human survival studies, suggests that a subgroup of Type B individuals (termed "Type C"--accepting, giving-up) are more likely to suffer a poor prognosis. A preliminary study relating Type A/B behavior pattern to cancer mortality was done in a cohort of 3154 men from the Western Collaborative Group Study (WCGS). The cancer mortality rate for the period 1960-1977 was 0.037 for Type A subjects (58 cancer deaths/1589 Type A subjects), and 0.025 for Type B subjects, yielding an odds ratio of 1.55. The odds ratio dropped to 1.29 (95% confidence interval = 0.84-1.96) when controlled for age, cigarette smoking, serum cholesterol, systolic blood pressure, and education. Preliminary analysis from a follow-up to mid-1983 shows a similar association. The findings suggest that, if anything, Type A subjects are more likely to die of cancer than Type B subjects. Although the finding is not strongly suggestive of a clinically or theoretically significant association between Type A/B behavior pattern and cancer mortality, it is sufficiently interesting to warrant further investigation.

The role of psychological factors in cancer incidence and prognosis.

The relationships between psychological variables and the presence of cancer, its prediction, and the prediction of cancer mortality and course of disease have been studied extensively. From a limited list of about 50 such variables, the following have been the focus of the most intensive research and are discussed in this report: human and animal stress; bereavement; depressed mood; psychosis, especially schizophrenia; suppression of emotions, especially anger; helplessness and hopelessness; social support; and psychotherapeutic intervention. For all of these variables, studies have shown both positive relationships and absence of relationships. The evidence against any such relationship is strongest for human stress, depressed mood, psychosis, and bereavement. Studies of animal stress show that it stimulates the development of cancers of viral origin and exacerbates their growth, while inhibiting the development and progression of chemically induced cancers. For the other factors, the literature remains contradictory.

Who says yes? Identifying selection biases in a psychosocial intervention study of multiple sclerosis.

The purpose of this work is to examine whether patients' sociodemographic and medical characteristics are associated with participation in a randomized controlled trial of two psychosocial interventions. After elimination of basic ineligibles from a registry of multiple sclerosis patients, 325 patients were sent a letter inviting participation in the randomized trial. Among those invited, 29% expressed an interest in participating, 19% scheduled an intake interview and 13% were actually randomized. chi 2 and logistic regression analyses were used to determine what factors were associated with successive stages of participation or non-participation in the study. Differential referral and participation rates could be traced in part to physician factors. With respect to patient factors, people were more likely to participate in the successive stages of recruitment if they had a higher median family income, lived a moderate distance from the hospital, and were disabled from working. Multivariate analyses of patient factors revealed that having a higher income and being disabled from work were the strongest predictors of participation, after adjusting for the effects of course of disease, disability status, and other sociodemographic predictors. Implications of these findings are discussed in terms of potential sources of bias in the selection of eligible patients, as well as the role the investigator may play in highlighting or underplaying this selection bias. Suggestions are made to minimize the bias-generating barriers.

Biological measures and cellular immunological function in depressed psychiatric inpatients.

Thirty depressed psychiatric inpatients, including 18 with a diagnosis of major depression, and 25 hospital staff controls were compared with respect to cellular immune function--that is, mitogen responsiveness to concanavalin A (con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM); natural killer cell (NK) activity; and T cell subsets, including helper/inducer T cells (CD4) and suppressor/cytotoxic cells (CD8). Only physically healthy subjects, who had not used psychoactive medications (except for low dose benzodiazepines) or other medications known to affect the immune system for at least 14 days, were included. Paired comparisons of the immune measures of patients with a DSM-III diagnosis of major depression (n = 18) with their controls demonstrated a statistically significant reduction of the patients' con A response. In addition, the patients with major depression had significantly lower con A and PHA responses than the combined patients with other forms of depression (atypical, dysthymic, or atypical bipolar). There was no indication that severity of depression, dexamethasone suppression test status, benzodiazepine use, or age accounted for the differences in immune function. A possibly important, unexpected finding was that antihistamine use was associated with lower immune function.

A hypothesis about Spiegel et al.'s 1989 paper on Psychosocial intervention and breast cancer survival.

In a randomized prospective study of 86 metastatic breast cancer patients by Spiegel et al. in 1989, the 50 who took part in a group psychosocial intervention survived on average 18 months longer than the 36 controls who did not. Because the control survival curve looked unusually steep, lacking an expected right-skewed tail, both curves were compared with that of a population from the same region having metastatic breast cancer. When transformed to life-table format, the curves of the control sample and the regional population, neither group having had an intervention, were almost identical for a year, and differed strikingly after 20 months. This led to the hypothesis that the 12 control patients surviving for more than 20 months were an extremely aberrant sample, being subject to the strong biasing influence of possible confounders, of which a considerable number are known, but not including those accounted for in the study. Corollaries to the hypothesis are that the intervention had no effect; that the intervention curve was in fact equivalent to a control curve with mild sampling departure from that of the regional population; and that, therefore, the repetition of the study now under way would not yield confirmation of the 1989 study, but rather, would support the hypothesis and the first two corollaries.

Remote life-style causes of cancer.

Most epidemiologists regard more or less proximal variables as life-style factors--smoking, diet, sex behavior, occupation. Within this framework, life-style factors making for high risk of cancer are defined and presented. Three estimates of the contribution to cancer incidence by the major proximal causes are presented, using the variables specified by each estimator. For purposes of completeness and possible prevention action, however, intermediate and distant precursors should be considered--local ecology, culture, industrialization, etc. The possibility that stress may affect cancer risk is addressed and evidence presented to suggest that any contribution to risk, if it exists at all, is probably small.

Premorbid psychological factors as related to cancer incidence.

In planning for studies relating psychological factors and/or stress (PF&/oS) to cancer, one should be aware of epidemiological findings that might contribute to or even account wholly for any found relationships. Most studies have not examined the known biological causes of cancer, nor have they described a rationale for relationships sought. The two broad mechanisms leading to cancer, carcinogens and lowered resistance to it, include physical and chemical causes, viruses and chronic infection, medication, genetic predisposition, hormonal stimuli, and aging. Interfering variables may bias or dilute a real relationship. Validity and reliability of instruments measuring PF&/oS are so variable as to warrant considerable care in their use. The latent periods of different cancers are measured in years, not months, with consequent potent impact on possible inferences drawn from prebiopsy and short prospective studies. In these and in retrospective studies, cancer can have strong and biasing effects on apparently straightforward PF&/oS measurements, as can iatrogenic effects. Some theoretical issues are discussed. The known prospective studies are discussed and reasons are given for the view that they are less convincing then many seem to think. A sketch of a model relating PF&/oS to cancer appearance is outlined, with some theoretical implications, and issues in research design are addressed.

Some problems and some solutions in research on psychotherapeutic intervention in cancer.

Several requirements of psychotherapeutic intervention (PI) research are presented. Some major problems are discussed. First, confidence in experimental results may be diminished by interference of possible confounders. A large number of these exist, both physical, perhaps more easily measurable, and psychological or psychosocial. Second, the value and limitations of randomization are presented, with special reference to small N. Validity and reliability are addressed, with emphasis on things that may dilute the strength of both of these measures. Natural remedies are proposed. Internal consistency and reliability are compared and cautions are given regarding their use and possible invalid substitution of consistency for reliability. Comparison of different PIs is commented on, with some relevant examples. Finally, a matter of special interest is discussed: the inconsistency between Spiegel's control survival curve and that produced from local population normative data.

Blood pressure, edema and proteinuria in pregnancy. 8. Evaluation of criteria.

We have reviewed some of the potential sources of errors in our study data with regard to the criteria used clinically to diagnose toxemia. The constraints imposed are rather clear. Despite these limitations (or perhaps because of them), we are impressed that the trends noted in the foregoing studies reported in this workshop relating to gestational progression and perinatal outcome have been encountered. Because such relationships have been uncovered using relatively coarse study parameters, we are tempted to infer that they are likely to be correct. If indeed such trends were spurious or weak relationships, the indelicate clinical signs at our disposal (in terms of their reliability and reproducibility) should not have been expected to demonstrate them so cogently. At the same time it should be made clear that more subtle correlations may exist, other than those herein shown, which perforce cannot be demonstrated or proved because of the restrictive unreliability of the clinical observations.

Suicide rates among cancer patients in Connecticut.

This study derives age-sex specific standardized mortality ratios (SMR's) among cancer (ca) patients with respect to population suicide rates. Suicide rates were derived for all 144,530 ca patients in the Connecticut Tumor Registry from 1940-1973. We also derived rates by number of years since diagnosis (y-s-dx) and by decade of dx. We hypothesized beforehand that suicide rates will (1) be higher in ca patients than the population; (2) be higher soon after dx than in later y-s-dx; (3) vary directly with spread of disease at dx, highest for metastatic, lowest for local. We address hypotheses (1) and (2) here. After collapsing age groups and y-s-dx in the observed 192 ca patient suicides, SMR's derived for age, sex and y-s-dx were tested with an exact Poisson distribution. Overall, SMR for males was significantly elevated (230, P less than 0.005), but not for females. In males, a test for trend in SMR's with y-s-dx showed a significant decline, supporting hypothesis (2) for males (chi2 = 4.0, df = 1, P less than 0.05). No trend was found for decade of dx. On combining decades, male SMR's were significantly elevated in 10 of the 25 cells of age by y-s-dx, while none of the female cells was significant. We conclude that both hypotheses were supported for males, and neither for females.

Short-term immunological effects of induced emotion.

Twenty healthy volunteers (half male) recalled and relived maximally disturbing (NEG) and maximally pleasurable (POS) emotional experiences. Forty minutes of silence, then neutral conversation, preceded and followed 40 minutes of emotion elicitation (NEG and POS randomly rotated). They were under video, cardiovascular, and immunological monitoring. Subjects reported appropriate emotions and showed significant cardiovascular activation during the NEG condition. Speech alone had an independent cardiovascular activating effect. Emotion, particularly NEG, led to further activation. NEG emotion promoted significant declines in mitogenic lymphocyte reactivity, followed by return to pre-emotion levels. A similar though less extreme decline was seen in the POS condition. There was a weak trend for elevated natural killer cell activity under the NEG condition, possibly due in part to changed trafficking patterns. Correlational findings confirmed these group effects. The decline in mitogenic reactivity during POS emotion appeared to be due to subtle degrees of tension and excitement triggered by the experimental experience regardless of the exact emotions recalled. Results suggest that immunologic processes are sensitive to influence by arousal of emotion.

Psychological factors in the prognosis of malignant melanoma: a prospective study.

Sixty-four patients with Stage I or II malignant melanoma who were apparently disease free rated the amount of adjustment needed to cope with their illness on a scale of 1 to 100. The resultant figure was called the melanoma adjustment score. Twenty-nine patients who relapsed within 1 year of surgery reported a score of 53 +/- 31 (mean +/- SD); 35 nonrelapsers reported a score of 80 +/- 20, p less than 0.001. Based upon analysis of indivual melanoma adjustment scores in the first 31 patients, we predicted that subjects scoring greater or equal to 65 would stay in remission, whereas those scoring greater than 65 would relapse. Applying this prospectively to the next 33 patients we correctly identified 25 of 33 outcomes (76%), p less than 0.03. This psychological variable was independent of known biological prognostic factors, which did not predict 1 year survival. The melanoma adjustment score was also independent of the number of positive lymph nodes, which did correlate with outcome in these patients. The results suggest a role for psychological factors in the one year prognosis of this malignancy.