Carl E. Speicher

Psychosocial modifiers of immunocompetence in medical students.

&NA; This study addressed the effects of a naturally occurring stressor on components of the immune response. Blood was drawn twice from 75 first‐year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Median splits on scores from the Holmes—Rahe Social Readjustment Rating Scale and the UCLA Loneliness Scale produced a 2 X 2 X 2 repeated measures ANOVA when combined with the trials variable. Natural killer (NK) cell activity declined significantly from the first to the second sample. High scorers on stressful life events and loneliness had significantly lower levels of NK activity. Total plasma IgA increased significantly from the first to second sample, while plasma IgG and IgM, C‐reactive protein, and salivary IgA did not change significantly.

Marital Quality, Marital Disruption, and Immune Function

&NA; Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self‐report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.

Chronic stress and immunity in family caregivers of Alzheimer's disease victims.

&NA; Although acute stress has been associated with transient immunosuppression, little is known about the immunologic consequences of chronic stress in humans. In order to investigate possible health‐related consequences of a long‐term stressor, we obtained blood samples for immunologic and nutritional analyses and psychologic data from 34 family caregivers of Alzheimers disease (AD) victims and 34 sociodemographically matched comparison subjects. Family caregivers for AD victims were more distressed than comparison subjects without similar responsibilities. Greater impairment in the AD victim was associated with greater distress and loneliness in caregivers. Caregivers had significantly lower percentages of total T lymphocytes and helper T lymphocytes than did comparison subjects, as well as significantly lower helper‐suppressor cell ratios; caregivers also had significantly higher antibody titers to Epstein‐Barr virus than did comparison subjects, presumably reflecting poorer cellular immune system control of the latent virus in caregivers. The percentages of natural killer cells and suppressor T lymphocytes did not differ significantly. These data suggest that chronically stressed AD family caregivers do not show immunologic or psychologic adaptation to the level of their well‐matched age peers.

Stress, loneliness, and changes in herpesvirus latency

This study used a prospective design to examine the influence of examination stress and loneliness on herpesvirus latency as measured by changes in antibody levels to three herpesviruses, Epstein-Barr virus (EBV), Herpes simplex type I (HSV-1), and cytomegalovirus (CMV). Three blood samples were obtained from 49 first-year medical students, with the first sample drawn 1 month before final examinations, the second on the first day of final examinations, and the third during the first week after their return from summer vacation. A median split on the UCLA Loneliness Scale divided subjects into high- and low-scoring loneliness groups. There were significant changes in the antibody titers to all three herpesviruses across the sample points, with the lowest levels found in the third (low stress) sample. High-loneliness subjects had significantly higher EBV antibody titers than low-loneliness subjects. These data suggest that stress-related immunosuppression can significantly modulate herpesvirus latency.

Modulation of Cellular Immunity in Medical Students

This study assessed the psychosocial modulation of cellular immunity in 34 medical-student volunteers. The first blood sample was obtained 1 month before examinations, and the second on the day of examinations. There were significant declines in the percentage of helper/inducer T- lymphocytes, in the helper/inducer-suppressor/cytotoxic-cell ratio, and in natural killer-cell activity in the blood samples obtained on the day of examinations. Half of the subjects were randomly assigned to a relaxation group which met between sample points; the frequency of relaxation practice was a significant predictor of the percentages of helper/inducer cells in the examination sample. Three biochemical nutritional assays (albumin, transferrin, and total iron-binding protein) were within normal limits on both samples. Data from the Brief Symptom Inventory showed significantly increased global self-rated distress associated with examinations in the no-intervention group, compared to nonsignificant change in the relaxation group. Clinical and theoretical implications are discussed.

Stress-related immune suppression: Health implications

This study used a year-long prospective design to assess linkages among distress, immunity, and illness. Serial blood samples were collected from 40 first-year medical students at the first, third, and fifth examination periods, as well as 1 month before each. There were significant decrements in the production of gamma-interferon by concanavalin A-stimulated lymphocytes obtained at the time of examinations. Antibody titers to Epstein-Barr virus (EBV) increased during examination periods, suggesting reactivation of latent EBV and therefore poorer cellular immune control of latent virus. We obtained data that suggest that T-cell killing by memory T lymphocytes of EBV transformed autologous B lymphocytes also declined during examination periods. The activity of a lymphokine, leukocyte migration inhibition factor, normally suppressed during recrudescence of herpes simplex virus type 2 infections, was altered during examination periods and an increase in both plasma and intracellular levels of cyclic AMP associated with examination stress was observed. An increase in the incidence of self-reported symptoms of infectious illness was also associated with examination periods. The data support the linkage between stress-related immunosuppression and health.

Urinary Cortisol Levels, Cellular Immunocompetency, and Loneliness in Psychiatric Inpatients

&NA; This study examined the associations among loneliness, stressful life events, urinary cortisol levels, and immunocompetency. Blood and urine were obtained from 33 psychiatric inpatients on the day after admission, at which time the patients completed the UCLA Loneliness Scale, the Psychiatric Epidemiology Research Interview Life Events Scale (PERI), and the MMPI. Patients who scored above the median on loneliness had significantly higher urinary cortisol levels. The high loneliness group also had significantly lower levels of natural killer cell activity, as well as a poorer T‐lymphocyte response to phytohemagglutinin. The high loneliness subjects described themselves as more distressed than the low loneliness group on the MMPI. There were no consistent significant effects on either the immunologic measures or the MMPI associated with the PERI.

Marital discord and immunity in males

&NA; While limited data suggest significant gender differences in mental and physical health risks following marital disruption, men have not been studied as intensively as women. In this study, self‐report data and blood samples were obtained from 32 separated or divorced men and 32 sociodemographically matched married men. Separated/divorced men were more distressed and lonelier, and reported significantly more recent illness than did married men; the former also had significantly poorer values on two functional indices of immunity (antibody titers to two herpesviruses), while not differing significantly on quantitative indices (percentages of helper and suppressor cells and their ratio). Among married men, poorer marital quality was associated with greater distress and a poorer response on one functional immunological measure, antibody to Epstein‐Barr virus (EBV), as well as lower helper/suppressor ratios. Among separated/divorced subjects, those who had separated within the past year and who had initiated the separation were less distressed, reported better health, and had a better performance on one functional immunological assay (EBV antibody titers) than did noninitiators. These data are discussed in the context of research on longer‐term adaptation to marital disruption.

Distress and DNA Repair in Human Lymphocytes

This research assessed differences in DNA repair in lymphocytes from high-and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.

Stress-related impairments in cellular immunity

The percentages of total T-lymphocytes (OKT-3+), helper T-cells (OKT-4+), and suppressor T-cells (OKT-8+) were significantly lower in blood samples obtained from 40 medical students during examinations, compared to baseline values obtained 6 weeks earlier. In addition, the response of T-lymphocytes to stimulation by phytohemagglutinin and concanavilin A was also significantly lower during examinations, compared to baseline. Self-report data documented significantly greater distress associated with examinations. The data have implications for immunosuppressive disorders and stress-related illnesses.