17
Marital Discord and Immunity in Males JANICE K. KIECOLT-GLASER, PHD, SUSAN KENNEDY, PHD, SUSAN MALKOFF, BA, LAURA FISHER, BA, CARL E. SPEICHER, MD, AND RONALD GLASER, PHD 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 mea- sure, 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. INTRODUCTION Epidemiological studies have demon- strated clear differences between married and unmarried individuals in mental and physical health: divorced and separated individuals have poorer mental and phys- ical health than comparable married, wid- owed, or single adults (1-3). Separated and divorced adults are disproportionately represented in both inpatient and outpa- tient psychiatric populations (2, 4). In ad- dition to greater psychological symptom- From the Departments of Psychiatry (J.K.K.-G., S.M., L.F.), Medical Microbiology and Immunology (S.K., R.G.), and Pathology (C.E.S.), and the Comprehensive Cancer Center (R.G.), Ohio State University College of Medicine, Columbus, Ohio. Address reprint requests to: Janice K. Kiecolt-Glaser, Ph.D., Department of Psychiatry, Ohio State Univer- sity College of Medicine, 473 West 12th Avenue, Co- lumbus, OH 43210. Received for publication July 13, 1987; revision received October 19, 1987. Psychosomatic Medicine 50:213-229 (1988) Copyright ® 1988 by the American Psychosomatic Society, Inc. Published by Elsevier Science Publishing Co , Inc. 52 Vanderbilt Avenue, New York, NY 10017 atology, separated/divorced adults have the highest rates of acute and chronic medical problems, including certain kinds of in- fectious disease, even when age, race, and income are controlled (5). Although it has been shown that there are clear epidemiological differences be- tween the married and unmarried in men- tal and physical health, few studies have examined health-related correlates of mar- ital quality within the married population (6). In fact, there is evidence that marital discord has important emotional and physiological consequences. Poorer mar- riages are reliably associated with in- creased distress, and unmarried people are happier on the average than those in trou- bled marriages (7-10). Moreover, unhap- pily married individuals also report poorer health than do either happily married or divorced people of the same race, sex, and age (11). Chronically abrasive marital relation- ships may have autonomic correlates, pro- 213 0033-3174/88/S3.50

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Page 1: Marital Discor andd Immunity in Malespni.osumc.edu/KG Publications (pdf)/031.pdf · marital quality. Some data suggest that women are more vulnerable than men to persistent marital

Marital Discord and Immunity in Males

JANICE K. KIECOLT-GLASER, PHD, SUSAN KENNEDY, PHD,SUSAN MALKOFF, BA, LAURA FISHER, BA, CARL E. SPEICHER, MD,AND RONALD GLASER, PHD

While limited data suggest significant gender differences in mental and physical health risksfollowing 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 32sociodemographically matched married men. Separated/divorced men were more distressedand lonelier, and reported significantly more recent illness than did married men; the formeralso had significantly poorer values on two functional indices of immunity (antibody titers totwo herpesviruses), while not differing significantly on quantitative indices (percentages ofhelper and suppressor cells and their ratio). Among married men, poorer marital quality wasassociated with greater distress and a poorer response on one functional immunological mea-sure, antibody to Epstein-Barr virus (EBV), as well as lower helper/suppressor ratios. Amongseparated/divorced subjects, those who had separated within the past year and who had initiatedthe separation were less distressed, reported better health, and had a better performance onone functional immunological assay (EBV antibody titers) than did noninitiators. These dataare discussed in the context of research on longer-term adaptation to marital disruption.

INTRODUCTION

Epidemiological studies have demon-strated clear differences between marriedand unmarried individuals in mental andphysical health: divorced and separatedindividuals have poorer mental and phys-ical health than comparable married, wid-owed, or single adults (1-3). Separated anddivorced adults are disproportionatelyrepresented in both inpatient and outpa-tient psychiatric populations (2, 4). In ad-dition to greater psychological symptom-

From the Departments of Psychiatry (J.K.K.-G., S.M.,L.F.), Medical Microbiology and Immunology (S.K.,R.G.), and Pathology (C.E.S.), and the ComprehensiveCancer Center (R.G.), Ohio State University Collegeof Medicine, Columbus, Ohio.

Address reprint requests to: Janice K. Kiecolt-Glaser,Ph.D., Department of Psychiatry, Ohio State Univer-sity College of Medicine, 473 West 12th Avenue, Co-lumbus, OH 43210.

Received for publication July 13, 1987; revisionreceived October 19, 1987.

Psychosomatic Medicine 50:213-229 (1988)Copyright ® 1988 by the American Psychosomatic Society, Inc.Published by Elsevier Science Publishing Co , Inc.52 Vanderbilt Avenue, New York, NY 10017

atology, separated/divorced adults have thehighest rates of acute and chronic medicalproblems, including certain kinds of in-fectious disease, even when age, race, andincome are controlled (5).

Although it has been shown that thereare clear epidemiological differences be-tween the married and unmarried in men-tal and physical health, few studies haveexamined health-related correlates of mar-ital quality within the married population(6). In fact, there is evidence that maritaldiscord has important emotional andphysiological consequences. Poorer mar-riages are reliably associated with in-creased distress, and unmarried people arehappier on the average than those in trou-bled marriages (7-10). Moreover, unhap-pily married individuals also report poorerhealth than do either happily married ordivorced people of the same race, sex, andage (11).

Chronically abrasive marital relation-ships may have autonomic correlates, pro-

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J. K. KIECOLT-CLASER et al.

viding evidence of one pathway throughwhich health might be affected. Levensonand Gottman (12, 13) found that greaterautonomic arousal in interacting marriedcouples was very strongly predictive ofsubsequent declines in marital satisfaction3 years later. Moreover, they also reportedthat greater declines in marital satisfactionwere strongly correlated with poorer healthratings at follow-up.

If the presence of a spouse in a disturbedrelationship is associated with greaterphysiological arousal over time [13], thenit is possible that there are concurrent en-docrinological alterations that could me-diate immunological changes (14, 15).Consistent with this, poorer marital qual-ity was associated with greater depressionand a poorer response on three functionalindices of the immune response in 38 mar-ried women (16).

Thus, an unsatisfactory marital rela-tionship may actually place an individ-ual at greater risk than does the absenceof a partner because it may itself be asource of stress, while simultaneouslyplacing limits on the ability to seek sup-port in other relationships (17). Such ef-fects are potentially very important be-cause marital discord is relativelycommon (6). For example, Waring andcolleagues (6) found that 31% of a sam-ple of 250 couples described their mar-riages as either emotionally distant ordeficient in level of intimacy. Similarly,20% of a large sample of adults under 45years of age said that they were unhap-pily married (11).

However, even the end of a marriagemarked by extreme marital discord doesnot necessarily prepare each spouse equallyfor divorce (18, 19), and there is consid-erable variation in individuals' ability tohandle the disruption and disengagement(20). Psychological adaptation following

separation appears to occur over a several-year period. Weiss (21) suggests that theestablishment of a more resilient and sta-ble identity may take 2 to 4 years. Wall-erstein and Kelly (19) found that it was anaverage of 2.2 years postseparation beforethe lives of the men in their sample as-sumed a sense of coherence, postdivorcereorganization, and stability (versus an av-erage of 3.3 years for women). However,31% of the men and 42% of the women intheir sample had not reached this point 5years after separation.

There may be persistent physiologicalchanges associated with the several-yearperiod of psychological adaptation tomarital disruption. Data from Cartwright(22) show depression-related alterationsin REM sleep that persisted 2 years afterdivorce in a small sample of women.Among 38 women who had been sepa-rated for up to 6 years, we found thatshorter separation periods and greatercontinued attachment to the (ex)husbandwere associated with poorer immunefunction and greater depression (16).These effects were most pronounced inthe women whose separation was mostrecent: the 16 women who had been sep-arated a year or less had significantlypoorer immune function than did theirsociodemographically well-matched mar-ried counterparts across five out of six ofour immunological assays.

Men's responses to separation and di-vorce have not been studied as intensivelyas those of women. However, limited datasuggest that there may be significant dif-ferences in both health risks and patternsof adjustment. Reviewing epidemiologicalhealth data, Bloom et al. (3) found thathealth risks were greater for separated anddivorced men than for women, includinggreater morbidity and mortality, as well asgreater psychopathology.

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MARITAL DISCORD AND IMMUNITY IN MALES

There are a number of other potentiallyimportant gender differences. For exam-ple, across a number of studies men appearto be less likely to initiate the separation;only a quarter to a third of marital sepa-rations are directly prompted by the hus-band's decision (23]. A number of studieshave suggested that postdivorce adjust-ment is easier for initiators, those individ-uals who take the primary responsibilityfor the decision to divorce (20, 24). It hasbeen suggested that being an initiatorprobably enhances one's sense of personalcontrol during a particularly stressful time(20); being an initiator is also associatedwith less continued attachment to the(ex)spouse (23, 25, 26), and thus with lessseparation distress. The rejected spouseoften experiences feelings of humiliationand powerlessness, sometimes accom-panied by considerable depression andanger (19). The effect appears to be muchstronger within the first year (26) after sep-aration.

In addition to sex differences in patternsof adaptation to separation and divorce,there is some evidence consistent withgender differences in the importance ofmarital quality. Some data suggest thatwomen are more vulnerable than men topersistent marital problems (9). Similarly,Gove, Hughes, and Style (10) concludedthat the affective quality of a marriage ismore critical for women, while marital sta-tus plays a more central role for men. Incontrast, others report little or no differ-ence; in fact, although women have higherrates of depression than men, the greatlyincreased risk for major depression in anunhappy marriage is about the same forwomen and men, about a 25-fold increase(27).

As previously described in an earlierstudy with women, we were interested inthe possibility that there were distress-

related alterations in immune function(28, 29) associated with marital disrup-tion, especially in view of the prolongedelevations in distress found across stud-ies for both sexes, and the associatedhealth risks. We investigated factors thatappear to moderate feelings of continuedattachment to the (ex) spouse in sepa-rated/divorced individuals, including timesince separation and initiator status (20,23, 30, 31).

We tested the following hypothesesconcerning marital quality and maritaldisruption in men: 1) It was expected ourseparated/divorced males (all of whom hadseparated within the past 3 years) wouldbe more distressed, would be lonelier, andwould have poorer immunological func-tioning than a sociodemographically andage-matched married comparison sample.2) While the evidence is mixed, we ex-pected that higher marital satisfactionwould be associated with better mentalhealth and immunological functioningamong married men (11, 32). 3) Within theseparated/divorced subject cohort, inter-actions between time since separation andinitiator status were predicted: i.e., it wasexpected that men who initiated the sep-aration and who had been separated a yearor less would have better psychologicaland immunological functioning than wouldnoninitiators who had been separated forthe same amount of time, with little dif-ference between initiators and noninitia-tors who had been separated more than ayear.

METHODS

SubjectsThe subjects were 32 separated/divorced men and

32 sociodemographically matched married men.About a quarter of the subjects were college stu-

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dents for whom experimental participation was onemethod of fulfilling a course requirement; thesestudents were recruited through announcementsmade in the evening classes that had older stu-dents. Another quarter of the subjects responded tonewspaper advertisements in a suburban newspa-per distributed free of charge to Columbus house-holds; the advertisements solicited married andseparated/divorced men for a research project onstress and health. The remaining subjects were re-cruited from responses to a newspaper story thatdescribed the project. The latter two groups of sub-jects were paid $10 for participation. The projectwas described to potential subjects during a tele-phone screening interview. The data were col-lected from groups of two to 10 subjects at a time,with concurrent data collection from married andseparated/divorced individuals.

As the study progressed we attempted to balancethe two groups on certain interrelated sociodemo-graphic dimensions, including age, education, lengthof marriage, relative number of childless marriages,and number of children. Other studies have empha-sized the importance of these variables as mediatorsof postdivorce adjustment (19, 30, 33).

While previous studies have suggested that up tohalf of all divorced individuals have participated ineither couples therapy or individual therapy beforeor after separation, there are not consistent datasuggesting that any kind of therapy either before orafter separation is systematically associated withbetter adaptation. However, the issue is probablyclouded by the greater propensity of more dis-tressed or symptomatic individuals and/or thosewith fewer interpersonal supports to seek treat-ment (23, 30).

The same health-related questions that were usedduring telephone screening were also included intheir questionnaire packet. Potential subjects couldnot be using any prescription or nonprescriptionmedication with possible immunological conse-quences, nor could they have any acute or chronichealth problems that might have an immunologicalor endocrinological component. Similarly, subjectswith recent surgeries were excluded, as were thosewho reported drinking more than 10 alcoholic drinksper week.

The separated/divorced group was limited to menwho had separated from their wives within the past3 years. We used the date of the actual separation,rather than the divorce date for those who had com-pleted formal court proceedings, because distress isgenerally thought to be maximal following separation(30).

Self-Report Data

History and Sociodemographic Data. Questionsincluded length of marriage, timing of separation anddivorce, and frequency and degree of satisfaction withdating relationships since the separation. FollowingPettit and Bloom (20), initiator status was determinedby the response to the question of who made thedecision to separate, with possible responses of 1) itwas completely my decision, 2) it was mostly mydecision, 3) it was a mutual decision, 4) it was mostlymy wife's decision, and 5) it was completely my wi-fe's decision. Pettit and Bloom noted that those sub-jects reporting mutual initiation did not differ fromthose who were initiators; however, they were bothclearly different from noninitiators.

Health status data included medication usage andrecent alcohol intake. Subjects were also asked howmany hours of sleep they had had in the past 3 days,as well as the amount of any weight changes in thepast week. They were asked the number of days theyhad been unable to perform their normal daily ac-tivities in the past 2 months because of acute illness.Subjects were asked to describe symptoms of anyillness, and only those that appeared to include in-fectious disease were counted.

Distress/Depression. The 53-item Brief SymptomInventory (BSI; 34) provided information on distress.The scales of particular interest for the present studywere the depression scale and the global severityindex (GSI), with the latter providing a summary dis-tress measure. Subjects rated the degree of associateddiscomfort during the past week for each item from0 (not at all) to 4 (extremely).

Marital Quality. The 32-item Dyadic AdjustmentScale (DAS; 35) was given to married subjects. TheDAS is one of the most commonly used scales inmarital research, and there are good data supportingits reliability and validity (24, 35, 36). Married menwere asked to respond on the basis of their relation-ship with their wives over the past 6 months.

Attachment. The primary conceptual frameworkused in the divorce literature to explain the postse-paration increases in physical and psychologicalsymptomatology is attachment theory (21). Attach-ment bonds, once formed, are extremely difficult tobreak; thus, the very ambivalent feelings toward the(ex)spouse reflect the persistence of attachment de-spite the erosion of love. The characteristic increasedsymptomatology ("separation distress") following

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marital disruption is a function of the inaccessabilityof the spouse (26). Since such bonds are normallyformed within the first 2 years of marriage (21), lengthof marriage is neither a good predictor of postdivorceadjustment nor a good predictor of attachment (23).Although distress and attachment are both related toa variety of situational changes produced by maritaldisruption, attachment feelings appear to cause dis-tress, rather than vice versa (23).

The items in Kitson's (23) attachment measure, usedin this study, assess preoccupation with the (ex)spouse,and disbelief about the separation/divorce. Responseson the four-point scale range from "not at all" to "verymuch," with higher scores indicating greater attach-ment. Research with the scale has provided evidencefor its reliability and validity (23,26,37).

Loneliness. Loneliness has frequently been re-ported as a problem for separated/divorced individ-uals (33, 19), particularly noninitiators (23). More-over, loneliness may be a longer-term problem foradults after divorce (38). Loneliness is also of interestbecause of its theoretical ties to the absence of at-tachment figures (39), and its association with de-pressed cellular immunity in medical students (40,41) and psychiatric inpatients (42). Subjects com-pleted the four-item survey version of the UCLALoneliness Scale (43, 44).

Locus o/ Control. As in previous research on ini-tiation (20), we included Rotter's locus of control scale(45). The scale was designed to help assess the possi-bility that differences in initiator status might simplyreflect underlying personality dimensions that mighthave their own mental and physical health correlates.

Life Changes. The Psychiatric EpidemiologicalResearch Inventory Life Events Scale (PERI; 46) wasused to assess the number of major life changes overthe past year. We were interested in the number ofnegative events, since health changes are reliably as-sociated only with negative events (47), and the num-ber of such events is as good a predictor as the weightedsum (48). The PERI was included to assess differ-ences in life changes related to initiator status andtime since separation that might mediate psycholog-ical and immunological effects.

Nutritional Data

Albumin was assayed to provide objective infor-mation on the nutritional status of subjects. Thereare well-documented impairments in various aspects

of immune function in undernourished individuals,and moderate to severe protein-caloric malnutritionis associated with increased frequency and severityof infection (49). Protein assays provide better infor-mation on global nutritional status than do those forcarbohydrates and fats, since the former have variednutritional building blocks, as well as very complexsynthetic pathways. The half-life of albumin is 2-3weeks.

The procedure used to measure albumin is an ad-aptation of the bromcresol green dye-binding methodof Rodkey (50), later modified by Doumas (51). Thisprocedure is recognized as a particularly good pro-cedure as compared to other dye-binding techniquesbecause of its specificity and freedom from interfer-ence.

Immunological Assays

A battery of four immunological assays providedinformation on both qualitative or functional andquantitative or enumerative aspects of cellular im-munity. The assays and the rationale for their inclu-sion are described below.

QuaJitative/Functional Assays. The two func-tional assays examined antibody titers to two latentherpesviruses: Epstein-Barr virus (EBV), the infec-tious agent for infectious mononucleosis, and herpessimplex virus using a type 1 antigen (HSV-1). Anti-body titers to latent herpesviruses provide an indi-rect measure of cellular immune system competency(52). For example, patients on immunosuppressivetherapies like chemotherapy or patients with im-munosuppressive diseases (e.g., AIDS) often have el-evated herpesvirus antibody titers; cessation of animmunosuppressive drug therapy is often followedby a drop in antibody titers. The increased herpes-virus antibody production in immunosuppressiveconditions is thought to reflect the humoral immunesystem's response to an increase in viral antigenssynthesized after reactivation. We have previouslyshown large and reliable stress-related changes inantibody titers to both EBV and HSV-1 in medicalstudents (41, 53), as well as a decrease in HSV-1antibody titers in elderly adults following a relaxa-tion intervention (54).

The indirect immunofluoresence (IF) assay was usedto measure antibodies to EBV virus capsid antigen(VCA) (41). Antibody titers were assayed using smearsof HR-1 cells. Cells were fixed in acetone at roomtemperature for 10 minutes, absorbed with twofolddilutions of plasma prepared in phosphate-buffered

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saline (PBS), pH 7.4, for 30 minutes at 37° C. Thecells were washed with PBS and reabsorbed withgoat antihuman IgG conjugated to fluorescein iso-thiocyanate (FITC) for 30 minutes at 37° C. The cellswere washed with PBS, counterstained with Evansblue, mounted in Protex, and examined with a ZeissUV microscope. Antibody titers were determined bythe highest dilution of plasma still able to demon-strate IF positive cells. All sides were read blind coded.

Vero cells were infected with HSV-1 and were usedto prepare the antigen for the enzyme linked im-munoadsorbance assay (ELISA). A protein assay (Bio-rad) determined the amount of protein present ineach antigen preparation. Antigen was added to 96-well plastic substrate plates (0.3 ml/well) and incu-bated at 4 °C overnight to allow the soluble antigento absorb to the plastic. Plasma dilutions were addedto the test wells. Previously characterized HSV-1—positive human sera were used to titrate each antigenas a control. An HSV-1-negative human serum wasalways used as a control. Goat antihuman IgG wasadded to each of the wells, the wells were washed,and then 2-2-azino-di-(3-ethylbenzthiazolin sulfo-nate) (ABTS), to which 3% hydrogen peroxide hadbeen added (0.3 ml to each well), was added. A darkgreen color change indicated a positive reaction. Thehighest dilution of antibody detected to HSV-1 wasdetermined by color change as compared to the neg-ative serum control (27). Antibody titers were deter-mined by optical density using a Flow LaboratoriesTitertek Multiscan MCC ELISA plate reader.

Although we used HSV-1—infected cells as the an-tigen, the specificity of the HSV antibody titer (HSV-1 versus HSV-2) is not known because there is cross-reactivity between the two strains. Any changes inHSV antibody titers, therefore, may reflect changesin antibody to either or both stains.

Quantitative/Enumerative Assays. Monoclonalantibodies were used to provide data on two quan-titative aspects of immune function, the relative per-centages of helper and suppressor T-lymphocytes.Helper T-cells stimulate a number of important im-munological functions, e.g., the production of anti-body by B-lymphocytes, an important defense againstinfections. Suppressor T-lymphocytes down-regu-late the activity of helper cells. Low helper/suppressorcell ratios are associated with immunodeficient con-ditions (55). Alterations in the percentages of helperand suppressor cells have been associated with ex-amination stress (56, 57).

Whole blood samples were obtained late in the day,and consequently were held overnight at room tem-perature in sterile RPMI1640 medium supplemented

with 2% fetal bovine serum and 5.0 ml 10% sodiumazide as a preservative. The following day, blood waslayered over Ficoll-Hypaque and centrifuged for 30minutes to obtain lymphocytes. Following careful as-piration of the lymphocyte layer, the cells were washedtwice with sterile RPMI medium. One million lym-phocytes were aliquoted into tubes for quantificationof helper/inducer T-cells and suppressor/cytotoxic cells,as determined using the monoclonal antibodies OKT-4 and OKT-8 (fluorescein isothiocyanate conjugate,Ortho). Five microliters of the appropriate mono-clonal were added to the cells, and the cells were in-cubated on ice for 30 minutes, washed twice with coldRPMI/PBS (1:1), and resuspended in 100 |xl parafor-maldehyde fixing solution. The cells were kept refrig-erated until read with an Ortho System 50 fluorescenceactivated cell sorter (FACS).

RESULTS

Table 1 provides sociodemographic in-formation on the married and separated/divorced cohorts. The two groups do notdiffer reliably on age, years of education,or occupation (coded with the Hollings-head), number of children, the (ex)wife'sage, or number of years married, all Fs <1. About 63% of the men in each samplehave one or more children, a percentagethat is consistent with epidemiological datasuggesting that about 60% of divorces in-volve families with children (30).

Overall Group Comparisons:Separated/Divorced vs. Married

Four MANOVAs were used for com-parisons between the entire married andseparated/divorced cohorts, one for thepsychological data, one for health-relatedbehaviors, and one each for the quantita-tive and functional immunological data(because of differences in variance). Thesewere followed by ANOVAs when there wasa significant main effect or interaction onthe MANOVA. These data are shown inTable 2.

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MARITAL DISCORD AND IMMUNITY IN MALES

TABLE 1. Subjects' Sociodemographic Characteristics

Separated/Divorced Men Married Men

AgeEducation

High schoolPartial collegeCollege graduateGraduate professional training

OccupationMajor and lessor professionals,

business managersAdministrative personnel, minor

professionals, clerical, salesSkilled, semiskilled, unskilledCollege student

Years marriedNumber of childrenNumber of childless marriages(Ex)spouse's age

34.02 (1.45)

61367

65

9.00 (1.45)1.23 (0.22)

12/3232.58(1.44)

33.73(1.38)

51836

9

9

59

7.84(1.15)1.28(0.22)

12/3231.15 (1.35)

TABLE 2. Means (±SEMs) for Psychological, Immunological, and Health Data

Separated/Divorced Men Married Men

Psychological dataBrief Symptom Inventory

Depression Scale"General Severity lndexb

UCLA Loneliness Scale"Immunological data

Qualitative/functional assaysEBV VCA antibody titersbc/

HSV-1 antibody titersb'd

Quantitative/enumerative assaysHelper T-cell percentagesSuppressor T-cell percentagesHelper/suppressor ratio

HealthDays reported ill, past 2 monthsc

63.56 (1.97)62.85 (1.94)9.41 (0.31)

248.45 (59.30)3142.76 (1005.98)

38.5419.582.18

1.91

(1.61)(1.28)(0.13)

(0.69)

53.41 (1.48)55.02 (1.56)7.67 (0.34)

92.06 (25.39)336.38(105.26)

37.8323.091.88

(1.74)(1.36)(0.14)

0.52 (0.18)ap < 0.001.bp<0.01.cp < 0.05.dHigher antibody titers to a latent herpes virus suggest that the cellular immune system is less competent in controllingvirus latency.

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There was a strong significant differ-ence between the married and sepa-rated/divorced groups on the psychologi-cal variables F(3,61] = 7.62, p < 0.001.Univariate ANOVAs were all significant,with greater distress in separated/divorcedmen, as predicted.

The groups differed significantly in daysof self-reported illness, F(l,63) = 3.74, p< 0.05. There was more illness reportedby the separated/divorced group. The twogroups did not show even marginal dif-ferences in health-related behaviors (weightloss, sleep, caffeine intake, and alcohol andcigarette use), F < 1. All subjects had val-ues within normal limits for albumin, thenutritional assay.

Since the method of doubling dilutionshad been used to obtain the EBV and HSVantibody titers, a base 2 logarithmic con-version was used to reduce variance forthe statistical comparisons and to nor-malize the distributions (58]. However, fordescriptive purposes the geometric meantiters (GMTs) are presented to allow com-parisons with previous research.

The MANOVA for functional aspects ofimmunity (antibody titers to EBV and HSV)was significant, F(2,58) = 5.69, p < 0.001,with married subjects having significantlylower antibody titers for both herpesvi-ruses than the separated/divorced group,suggesting that the cellular immune re-sponse was less competent in controllingherpesvirus latency in separated/divorcedmen. The MANOVA for the quantitativeassays was not significant.

Marital Quality: Importance AmongMarried Men

Marital quality was not significantly dif-ferent for those subjects who had childrenand those who did not, F < 1. DAS scoresdid not correlate significantly with num-

ber of children, r = 0.11. There were notsignificant correlations between maritalquality and a number of variables, includ-ing age (r = -0.13) or education (r =— 0.16). However, there was a significantcorrelation between years married andmarital quality, r = -0.31, p < 0.05, con-sistent with other research (1), so yearsmarried was entered in the regressionequations as described below.

Multiple regression equations were usedto evaluate the contribution of marital qual-ity to psychological and immunologicalfunctioning. Using a hierarchical proce-dure, the subject's educational level wasentered on the first step, number of yearsmarried was entered on the second step,and marital quality was entered on the thirdand final step. This analysis provides astricter evaluation of the contribution ofmarital quality, since lower education hasbeen associated with greater distress andpoorer health, and longer marriages tend tobe rated as somewhat less satisfactory (1).

As can be seen in Tables 3 and 4, poorermarital adjustment was a strong and signif-icant predictor of BSI depression and GSIscores, as well as loneliness, even after tak-ing out the significant contribution of edu-cation and length of marriage. Marital qual-ity was also strongly and positively relatedto EBV VCA antibody titers, suggestingpoorer cellular immune system control ofvirus latency. While the variables did notsignificantly predict values for helper cellpercentages, marital quality was signifi-cantly related to percentages of suppressorcells and the helper/suppressor ratio.

Marital Disruption:Separated/Divorced Men

The length of marital separation rangedfrom 1 month to 3 years. Both the meanand median separation lengths were about

220 Psychosomatic Medicine 50:213-229 (1988)

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MARITAL DISCORD AND IMMUNITY IN MALES

TABLE 3. Education, Years Married, and Marital Quality as Predictors ofPsychological Functioning in Married Men

BSI Depression ScaleStep 1:EducationStep 2:Years marriedStep 3:Marital quality

BSI General Severity IndexStep 1:EducationStep 2:Years marriedStep 3:Marital quality

UCLA Loneliness ScaleStep 1:EducationStep 2:Years marriedStep 3:Marital quality

Simple r

0.17

-0.04

-0 .63

0.29

-0.25

-0 .37

0.49

-0.11

-0 .56

r2

0.03

0.03

0.45

0.08

0 15

0.32

0.24

0.26

0.58

Beta

0.05

-0.25

-0 .69

0.22

-0 .39

-0 .44

0.40

-0.31

-0.61

t Entries

0.41

-1.75

-4.70 a

1.43

-2 .43 b

-2.66C

3.28C

-2 .46 b

-4.74a

F Steps

0.91

0.47

7.91°

2.76

2.63

4.46C

10.01c

5.26C

13.5Vap < .001.bp < 0.05.cp < .01.

1.75 years. Eight subjects were separatedbut not yet divorced.

Subjects were classified as initiators ifthey said that the decision was mostly theirsor a mutual one (20). With the use of thesecriteria, 14 of the 32 subjects were clas-sified as initiators, with only three of thesesaying the decision was mutual.

Two-factor MANOVAS were used to ex-amine the main effects and interactionsattributable to initiator status and time sinceseparation (less than or greater than a year),following the same clusters of variablesthat were used for the overall group com-parisons described previously. Two vari-ables were included as covariates for theseanalyses: education and age. The formerwas included because individuals with lesseducation report greater distress following

marital disruption (24). Age was includedas a covariate because of a significant dif-ference between initiators (mean of 29.21,SEM of 1.51) and noninitiators (mean of37.32, SEM = 2.02). The two groups didnot differ on any of the other sociodemo-graphic dimensions.

Initiators' scores on locus of control andnumber of negative life events were com-pared with those of noninitiators to assesspossible underlying personality differ-ences that might have mediated the ob-served effects. There were not differencesbetween the two groups on these variables,F < 1.

The MANOVA for psychological vari-ables included the attachment scale score,in addition to the loneliness score and theBSI depression and GSI scales. There was

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TABLE 4. Education, Years Married, and Marital Quality as Predictorsof Immune Function in Married Men

EBV VCA antibody titersStep 1:EducationStep 2:Years marriedStep 3:Marital quality

Helper T-lymphocytesStep 1 :EducationStep 2:Years marriedStep 3:Marital quality

Helper/suppressor ratioStep 1:EducationStep 2:Years marriedStep 3:Marital quality

HSV antibody titersStep 1:EducationStep 2:Years marriedStep 3:Marital quality

Suppressor T-lymphocytesStep 1:EducationStep 2:Years marriedStep 3:Marital quality

Simple r

0.49

0.32

-0.11

-0.15

0.09

0.15

-0 .28

-0 .23

0.32

0.32

-0.12

-0 .18

0.19

0.36

0.24

r2

0.24

0.30

0.40

0.02

0.03

0.05

0.08

0.13

0.33

0.10

0.12

0.16

0.04

0.16

0.31

Beta

0.47

0.39

-0.33

-0 .18

0.05

0.14

-0 .36

-0.35

0.48

0.36

-0 .06

-0.21

0.25

0.47

0.42

t Entries

3.05*

2.36a

-2.08a

-0 .89

0.29

0.65

-2.15a

-2.02a

2.72fa

1 95a

0.35

-1.12

1.49

2.70a

2.40a

F Steps

8.676

5.90b

3.37a

0.59

0.41

0.41

2.36

1.87

4.03"

3 50

1.99

1.76

1.04

2.44

3.84a

ap =s 0.05.bp =£ .01.

a significant main effect for initiator status, itiator status for the BSI GSI scale, F(l,26)F(4,24) = 3.50, p < 0.05, with only the = 4.48, with a similar marginal interac-expected difference between initiators and tion for the BSI depression scale, p < 0.06.noninitiators reaching significance in the Means for the BSI GSI showed maximumunivariate comparisons, p < 0.05. How- differences in the first year, with initiatorsever, there was also a significant interac- having a mean of 59.75 (SEM = 5.34), andtion between time since separation and in- noninitiators having a group mean of 70.13

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MARITAL DISCORD AND IMMUNITY IN MALES

(SEM = 5.08). Those initiators separatedmore than a year had a GSI mean of 64.37(SEM = 3.02], compared to 58.10 (SEM =3.18) for noninitiators.

The MANOVA to examine health-re-lated behaviors did not show a significantmain effect for either initiator status, F(5,23)= 2.10, or for time since separation, F <1. The interaction was similarly nonsig-nificant, F(5,23) = 1.16.

There was a main effect for initiator sta-tus on the MANOVA for the functionalvariables, F(2,25) = 4.09, p < 0.05, withlittle variance attributable to time sinceseparation or the interaction of the twovariables, Fs < 1. Initiators had signifi-cantly lower antibody titers to EBV VCAthan noninitiators, F(l,25) = 5.63, p <0.05. The mean for initiators was 124.28(SEM = 55.48), compared to 342.35 (SEM= 86.71) for noninitiators, suggestingpoorer cellular immune system control overvirus latency in the latter. Antibody titersto HSV followed the same pattern, but didnot reach significance.

The MANOVA that included the threequantitative variables did not show a sig-nificant main effect for either initiator sta-tus or time since separation, Fs < 1. Theinteraction was similarly nonsignificant, F< 1.

There was a significant interaction be-tween initiator status and time since sep-aration in the number of self-reported daysill in the past 2 months, F(l,26) = 6.63,with nonsignificant main effects for bothof the independent variables, Fs < 1. Whilethose who initiated the separation withinthe past year reported an average of only0.20 days ill, noninitiators separated withinthe past year reported an average of 3.63days ill. This pattern was reversed amongthose separated more than a year, with amean of 3.56 for initiators, compared to0.41 for noninitiators.

No hypotheses were made concerningthe effects of having children or beingchildless, since past divorce research doesnot support consistent positive effects foreither condition; similarly, there is notconsistent evidence indicating that cus-tody arrangements are differentially as-sociated with adaptation in men (26, 30,32). However, in order to evaluate the pos-sible impact of custody arrangements ondistress and loneliness within this sample,we compared the 10 fathers who did nothave custody with those who had custodyor shared joint custody (n = 6). There werenot even marginal differences between thegroups for the distress and loneliness vari-ables.

DISCUSSION

The separated/divorced men were sig-nificantly more distressed and lonelier thanvery well-matched married men. In addi-tion, they reported more recent illness, andthey had significantly higher antibody ti-ters to EBV VCA and HSV, suggestingpoorer cellular immune system control overherpesvirus latency. The two groups didnot differ on health-related behaviors, andall subjects were within normal range onalbumin, the nutritional marker. These dataare consistent with considerable epide-miological research that has linked maritaldisruption with high rates of psychologi-cal and physical dysfunction, particularlyfor males (3). Related research has shownthat widowers have a poorer blastogenicresponse after bereavement than they hadpreviously (59).

Poorer marital quality in the married co-hort was significantly related to greaterdepression and global distress, greaterloneliness, a poorer response on one of thefunctional immunological assays, and

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J. K. KIECOLT-GLASER et al.

lower helper/suppressor ratios. Consistentwith previous reports linking the qualityof the marital relationship with mental andphysical health (11), these data providefurther evidence for the importance of sat-isfactory marital relationships. As notedearlier, it has been suggested that maritalstatus is a more critical variable than mar-ital quality in men as compared to women(9, 10); while there may (or may not) berelative sex differences, marital quality wassignificantly related to both the psycho-logical variables and certain aspects of im-mune function in this sample.

The predicted interaction between ini-tiator status and time since separation wasfound in the data on psychological dis-tress, with less distress shown by thoseinitiators who had separated within thepast year. Self-reported health showed asimilar pattern in the first year after sep-aration, with greater illness among non-initiators; however, there was an unex-pected reversal of this pattern among thosemen who were separated more than a year.While little work has been done on lon-gitudinal differences between initiators andnoninitiators among men, Wallerstein andKelly (19) have described a subset of womenwho initiate the divorce, then strongly re-gret their action several years later. Simi-larly, a number of men studied by Heth-erington and colleagues (60) were pleasedwith the opportunities for diverse datingand sexual experiences during the first yearafter divorce. However, by the end of thisperiod, these men generally wanted lesstransient and more meaningful relation-ships. It is possible that the noninitiatorsin our study faced the issues of lonelinessand lack of a stable relationship earlier,and thus had dealt with them better by theend of the first year after separation, whileit took initiators longer to face these issues.Overall, those separated/divorced men who

had initiated the separation describedthemselves as significantly less attachedto their (ex)wives, and they had signifi-cantly lower antibody titers to EBV VCA,although the difference did not reach sig-nificance for HSV antibody titers.

In contrast to our findings with previousdata on separated/divorced women, we didnot find that time since separation was re-liably related to distress or immune func-tion. However, for this study we selectedsubjects who had been separated for nomore than 3 years, so time since separationwas much less variable in this sample thanin our previous sample. Moreover, rela-tionships have been found between initi-ator status but not time since separationin several other studies (23, 25, 26); Span-ier and Thompson (24) suggest that timesince separation may be a somewhat lesssensitive variable in cross-sectional stud-ies.

There are clear impediments to infer-ences about the direction of causality incross-sectional studies such as this wherethe subject sample is not randomly cho-sen. For example, the social selection hy-pothesis asserts that emotionally unstableor physically handicapped individuals areless likely to get married or to stay married(3). In this framework it is possible thatpreexisting depressive symptoms couldhave been an underlying cause for maritaldisruption in the separated/divorced group(3) and/or such symptoms might have in-terfered with the subsequent formation ofalternative relationships. Similarly, moredistressed married men may see their mar-ital relationship as less supportive, and/ortheir depressive symptoms may have ad-versely affected the quality of the maritalrelationship (61). These possibilities can-not be excluded; however, evidence fromother research supports alternative expla-nations.

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While research with psychiatric patientpopulations has supported the social se-lection hypothesis, evidence from normalpopulations strongly suggests that socialselection is not a primary determinant ofthe relationship between marital status andmental health (10). For example, Gove etal. (10) found that the quality of a marriageand not marriage per se was associated withbetter mental health after controlling forproblems individuals had experiencedearlier in life that are associated with greatervulnerability. Similarly, a 1-year longitu-dinal study from Monroe et al. (62) showedthat subsequent depressive symptoms werepredicted by lower marital support in 473women who were initially relativelyasymptomatic and had nonconflicted mar-riages. Controlling for level of depressionprior to marital termination, Menaghan (63)found that depression appeared more likelyto be the result of marital disruption, ratherthan vice versa, in longitudinal survey data.

Verbrugge (5) suggests that nonmarriedindividuals may have riskier life styles thando married adults, e.g., they may drink,smoke, or use drugs more; nutrition andsleep may also differ by marital status.Subjects who reported drug or alcoholabuse were excluded from this sample.Nutrition, weight, and sleep data did notdiffer as a function of marital status in oursample. Thus, while it is likely that risk-related life-style factors influence healthstatus in the general population, our datasuggest that there may be potentially im-portant physiological differences in indi-viduals who do not differ on obvious risk-related variables.

The immunological differences be-tween the married and separated/divorcedmen are consistent with the growing evi-dence that there may be persistent down-ward alterations in some aspects of im-mune function associated with "chronic"

stressors that last over periods of 1 or moreyears. Baum and colleagues (64) haveshown changes in endocrine and immunefunction in the several years following apotential disaster. Similarly, family mem-bers who have cared for an Alzheimer'sdisease victim over a period of several yearshave poorer immune function than do theirwell-matched community counterpartswithout similar responsibilities (65). Whilethe physiological mechanisms for thesemore persistent effects are not well under-stood, Baum's data (64) suggest that thereare concurrent longer-term endocrinechanges that may mediate some of the ob-served effects.

With regard to the immunological data,it appears that the functional assays (an-tibody titers to EBV and HSV, reflectingchanges in cellular immunity) were moreconsistently related to the psychologicalvariables than were the quantitative as-says; this finding is consistent with priorresearch from our laboratory (16). As hasbeen true in previous work, herpesvirusantibody titers appear to be quite sensitiveto psychological stressors, and may reflectmore general alterations in functional orqualitative aspects of immunity (66).

In an earlier study with medical stu-dents (16), additional assays were run torule out the possibility that the elevationsin EBV VCA antibody titers reflected anepidemic of infectious mononucleosis inpreviously uninfected (seronegative) stu-dents, or more general changes in plasmaIgG levels. None of the plasma samplesthat was tested had measureable levels ofEBV VCA IgM, an antibody that is char-acteristically elevated following the pe-riod of initial EBV infection. Moreover, an-tibody levels to EBV, HSV, andcytomegalovirus (another human herpes-virus) were reactive to academic stressors;in contrast, antibody to poliovirus type 2,

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J. K. KIECOLT-GLASER et al.

a recall antigen that is not associated witha latent infection, remained stable acrossthe sample points. Taken together, thesedata suggested that the observed herpes-virus antibody changes did not reflect eitheracute infectious mononucleosis or moregeneral changes in plasma IgG. Thus, thedifferences in herpesvirus antibody titersobserved in this study are thought to re-flect more general changes in cellular im-mune system competency (16).

Other research with medical studentsubjects has provided evidence of im-munological changes related to altera-tions in the control of the latent herpes-viruses; for example, using a year-longprospective design we found that cellkilling by memory T-lymphocytes of EBV-transformed autologous B-lymphocytesdeclined during more stressful examina-tion periods, compared to baseline pe-riods (53). Antibody titers to EBV wereconcurrently elevated during the exami-nation periods, as in previous research(41). Moreover, the activity of a lym-phokine, leukocyte migration-inhibitionfactor, normally suppressed during re-crudescence of herpes simplex virus type2 infections, was altered during exami-nation periods, as were both plasma andintracellular levels of cyclic AMP. Takentogether, these data provide evidence ofimmunological pathways that might leadto the alterations in herpesvirus latency,as evidenced by the differences in anti-body titers. Students concurrently re-ported more illness in conjunction withexamination periods.

Another recent study found similar con-current immunological and health changes,and suggested one mechanism throughwhich interpersonal relationships mighthave a relationship to immunity and health.Fifty healthy undergraduates were as-signed to write about either traumatic ex-

periences or superficial topics for 4 con-secutive days (67). Changes observed intwo measures of cellular immune systemfunction and health center visits suggestedthat confronting traumatic experiences maybe physically beneficial; these data areconsistent with evidence that individualswho undergo psychotherapy show re-duced utilization of medical services,relative to nonpsychotherapy controls(68).

In a conceptual framework elaboratedelsewhere (69), we have suggested that anincrease in psychological distress, sus-tained over time, can lead to adverse im-munological changes. These distress-re-lated immunological changes provide onepossible pathway through which major andminor life changes could lead to an in-creased incidence of infectious disease. Ifpsychological resources like supportiveinterpersonal relationships moderate dis-tress, they should also concurrently atten-uate adverse immunological changes. Whilethe critical connections between stress-re-lated immunological alterations and ac-tual health changes are not well estab-lished, these data and others areincreasingly suggesting a confluence of in-creased distress, poorer immune function,and a greater incidence and/or severity ofinfectious illness. Longitudinal studies areneeded to better understand the magni-tude of the relationship.

This study was supported in part by grantNo. 1 R01 MH40787from the National In-stitute of Mental Health, and by the OhioState University Comprehensive CancerCenter grant No. CA-16058-09, from theNational Cancer Institute, National Insti-tutes of Health. We are very grateful forthe excellent work on this project done byKathleen Tarr, Paula Ogrocki, and PaulVespa.

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