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Psychosomatic Medicine 66:965-972 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Intimate Male Partner Violence Impairs Immune Control Over Herpes Simplex Virus Type 1 in Physically and Psychologically Abused Women

M. Isabel Garcia-Linares, BA, Segunda Sanchez-Lorente, BA, Christopher L. Coe, PhD and Manuela Martinez, MD, PhD

From the Department of Psychobiology, Faculty of Psychology, University of Valencia, Spain (M.I.G.-L., S. S.-L., M.M.); and the Department of Psychology, University of Wisconsin, Madison, Wisconsin (C.L.C.).

Address correspondence and reprint requests to Manuela Martinez, MD, PhD, Department of Psychobiology, Faculty of Psychology, University of Valencia, Avda Blasco Ibañez, 21, 46010 Valencia, Spain. E-mail: Manuela.Martinez{at}uv.es


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: Intimate partner violence (IPV) against women is a worldwide problem and a cause of significant distress and threat to health. Studies have focused mainly on mental health, and few have considered the effect on physiological systems. The aim of this research was to determine whether IPV also compromises the immune system, as evidenced by a decrease in immune regulation over herpes simplex virus type 1 (HSV-1), the latent virus that causes cold sores.

METHODS: Physically abused (N = 47) and psychologically abused women (N = 27) were compared with nonabused control women (N = 37). Information about sociodemographic characteristics, lifetime history of victimization, and mental health status (depression, anxiety, and posttraumatic stress disorder) was obtained through structured interviews. Salivary samples were collected on two occasions, and the capacity to neutralize live HSV-1 virus was tested with a bioassay. In addition, salivary levels of HSV-1–specific antibody and total IgA were determined by enzyme-linked immunosorbent assay.

RESULTS: Physically abused women had the lowest virus neutralization, significantly below the other two groups, with the psychologically abused group intermediate. HSV-1–specific antibody also tended to be lower in physically abused women, but these values were not directly correlated with virus neutralization, suggesting that loss of other antiviral factors accounted for the reduced bioactivity. The effect of IPV on immune function was not mediated directly by mental health status.

CONCLUSION: These findings confirm that the stressful disturbance associated with IPV has important physiological consequences, which could impair health by increasing the likelihood of viral reactivation and reducing the ability to suppress virus proliferation.

Key Words: intimate partner violence, • herpes simplex virus type 1, • women, • depression, • anxiety, • posttraumatic stress disorder.

Abbreviations: IPV = intimate partner violence;; HSV-1 = herpes simplex virus type 1;; PTSD = posttraumatic stress disorder;; BDI = Beck Depression Inventory;; STAI = Spielberger State-Trait Anxiety Inventory;; CPE = cytopathologic effects;; HSV-1–sIgA = specific antibody against herpes simplex virus type 1;; IgA = immunoglobulin A;; ANOVA = analysis of variance;; EBV = Epstein-Barr virus;; sIgA = secretory immunoglobulin A.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Intimate partner violence (IPV) against women is considered a major public health problem because of its high prevalence in most societies and its effect on women’s well-being (1–3). To date, most studies have focused on mental health, with only a small proportion assessing its effect on physical health (4). Abused women have an increased prevalence of mental disorders (5–8). The limited research on physical health has documented an increase in psychosomatic symptoms and a higher occurrence of several chronic illnesses (9–12).

Intimate partner violence is considered a major source of social stress for women. Thus, it should be expected that some biological functions might be altered by this experience, as found for other types of human victimization (eg, childhood abuse and rape; 13–19). However, to date, there are relatively few studies on the physiological consequences of IPV, such as on the endocrine (20,21) and immune systems (22,23), or on neuropsychological functions (24) and brain morphometry (25). Regarding the immune system, Constantino et al. (23) found that T-cell function was lower in women victims of IPV in comparison with control women. Brokaw et al. (22) have also reported an effect of IPV on red blood cell function, microcytosis, which could be indicative of a risk for anemia or abnormal cell turnover.

The main aim of this study was to determine whether IPV affects the regulatory immune control over the latent virus herpes simplex type 1 (HSV-1). By adulthood, more than 90% of the population has been exposed to one or more herpes viruses, and most have manifested overt symptoms, including cold sores (HSV-1), chicken pox blisters (herpes zoster), or mononucleosis (Epstein-Barr virus [EBV]; 26–29). The first two viruses are considered neurotrophic. More than a century ago, it was observed that HSV-1 resides preferentially in the facial nerves after the primary infection and after its periodic recrudescence (30). Viral reactivation and the occurrence of symptoms can be elicited by physical trauma to the nerve, fever, exposure to excessive ultraviolet light, or chronic stress, resulting in the common lesion in the mouth or lip region (31–33).

Although it has been difficult to document that psychological stress leads to a large statistical increase in symptoms related to herpes viruses, there is strong evidence that many common negative life events, including school examinations and marital divorce, can stimulate viral activation (34–37). A number of stress-related neuroendocrine and immune factors have also been implicated in promoting viral replication, including adrenaline and corticosteroids (38–40). Conversely, any environmental event or endogenous process that would inhibit beneficial neurotrophic proteins, such as nerve growth factor, and the integrity of neurons, can stimulate HSV activation (41). This study was designed to focus on immune factors involved in the regulatory control of the HSV-1 virus rather than to assess the temporal fluctuation in overt symptom expression (42). The specific goal was to investigate whether HSV-1–related immunity in saliva was impaired in women who had experienced IPV.

It is difficult to consider IPV as an isolated psychosocial variable, because it may be superimposed on a history of childhood or other types of adulthood abuse (43,44). Thus, the second aim of this study was to determine whether the effects of IPV on HSV-1 would be compounded by a cumulative history of previous abuse. Additionally, because IPV has a high impact on mental health, the mediating effect of mood state was assessed.

Evaluations of the effect of IPV usually focus on physical and sexual violence, with fewer studies paying attention to psychological abuse alone. This emphasis occurs despite the finding that emotional maltreatment can be as devastating as physical assaults (10,45–47). Thus, the third aim of this study was to determine whether there was any distinction between those women experiencing only psychological abuse versus the dual effect of physical and psychological IPV.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
The present analyses were part of a larger research project on the effect of IPV on health, performed between 2000 and 2002 on a sample of 182 women from the Valencian Community of Spain. Women victims of IPV were recruited from several centers for helping women, and control women who lived in a nonviolent partner relationship were recruited through women’s clubs. All participants were of Spanish nationality. The study was approved by the University of Valencia research ethics committee, and previous informed written consent was obtained from participants. Approval to conduct the biological analyses of the salivary specimens was obtained from the Institutional Review Board of the University of Wisconsin.

Procedure
The study consisted of a structured interview during which four trained female psychologists asked about the women’s life and health. In general, each woman was interviewed by the same psychologist four to six times, with each session taking 1.5 hours. Additionally, the women were asked to provide saliva samples.

Questionnaires
A comprehensive questionnaire was designed for the face-to-face interview. The majority of questions were devised to yield objective factual reports. The questionnaires from which information for the present study was obtained are described below.

Sociodemographic Characteristics
Information about age and level of education was obtained.

Violence Perpetrated by an Intimate Male Partner
Detailed information about the different types of violence (physical, sexual, and psychological) perpetrated by the batterer was obtained. Each type consisted of one or more of the acts described below. Women were asked to answer yes or no to the incidence of each act.

Physical violence included punches, kicks, slaps, pushes, bites, and strangling.

Sexual violence included forced sex (vaginal or anal penetration, oral sex from her to him, or from him to her, objects inserted in vagina or anus); forced to have homosexual sex, to have sex with animals, to prostitute herself, or to have sex in public; physical violence during sexual intercourse (bites, kicks, blows, and slaps); threats to hit the woman or children if rejecting sex, including threats with knives, guns or other weapons; involvement of children in forced sex or witnessing sexual attacks; and use of pornographic films and photos.

Psychological violence included verbal attacks (insults, humiliations), control and power (isolation from family and friends, impeding decision making, economic abandonment), pursuit and harassment, verbal threats (woman’s and family’s life threatened, threats regarding the custody of children, intimidating phone calls), and blackmail (economic or emotional).

Control women were also asked all these questions to ensure that they had had no experience of IPV.

Endorsement or not of any of the acts of physical, sexual, or psychological violence was used as the criterion to designate women as abused or nonabused. The occurrence of any acts of physical violence was used to distribute abused women into two groups: physically abused and psychologically abused.

Lifetime History of Victimization
For childhood abuse, women were asked about the incidence of physical, sexual or psychological abuse during childhood. Physical abuse was defined as above. Sexual abuse included one or more of the following acts: forced sex, forced to touch a male’s sexual organs or being touched, forced exposure to the display of sexual organs, and threats of forced sex. Psychological abuse was defined as above except for the following acts, which were not included: threats regarding custody of children, and impeding decision making.

For adulthood victimization, women were asked about their experience of violence during adulthood independent of their being battered. Physical, sexual, and psychological violence was defined as described for childhood abuse.

Besides the number of violent acts, a score for each type of victimization was obtained by averaging the corresponding standardized scores of number of violent acts, frequency, and duration.

Mental Health
Mental health was measured by means of three indicators: the severity of depression and anxiety and the manifestation of posttraumatic stress disorder (PTSD) at the time of the study. Depressive symptomatology was measured with the Beck Depression Inventory (BDI; 48), state anxiety symptomatology with Spielberger State-Trait Anxiety Inventory (STAI; 49), and the Severity of Symptoms Scale of PTSD based on DSM-IV criteria (50). The correlations among standardized total scores on the three indicators of mental health were submitted to a principal component analysis. Only one component with an eigen value greater than 1 (2.0) was obtained. This component explained 66.8% of the observed variance. Thus, these results support the validity of using a mental health measure in regression analyses to test for mediational effects.

Saliva Samples
Saliva samples for the analysis of the immune control over the latent HSV-1 virus were collected. The participants provided a minimum of 0.5 ml saliva in a plastic tube twice a day (08:00–09:00 hours and 20:00–21:00 hours) for 2 days spaced 2 weeks apart, starting the ninth day after the beginning of menstruation. Saliva samples were frozen in the women’s freezer and brought to the freezer of the Department of Psychobiology in a mobile freezer, then kept frozen at –21°C. The volume and the time to collect the saliva drool were recorded, which permitted the determination of any group differences in mean flow rate (ml/min). Finally, all samples were sent to the University of Wisconsin for analysis.

Immune Assays
Frozen specimens were shipped to the United States and maintained in an ultracold freezer (–60°C) until assayed. A daily pool of sterilized saliva was generated for each woman by combining equal 2 ml aliquots from the morning and afternoon collection, diluting the saliva 1:1 with phosphate buffered saline, and passing it through a sterilizing millipore filter (0.45 µm; Gelman Sciences, Ann Arbor, MI). This preparation step generated two daily replicates of particulate-free saliva of similar viscosity for each woman, which was used for the three assays.

Herpes Neutralization
Neutralizing capacity was determined by serially diluting the samples and testing the ability of saliva to inhibit the formation of virus-induced cytopathologic effects (CPEs) in Vero cell cultures incubated with HSV-1. Briefly, 5 x 105 Vero cells (a HSV-1–sensitive epithelial cell line derived from monkey kidney) were grown in 2 ml Dulbecco’s Minimal Essential Media (with 5% fetal bovine serum), and then 200 µl was added to each well in a 24-well plate to create a monolayer. Next, HSV-1 stock solutions of 108 tissue culture infectious doses/ml were diluted to generate 100 tissue culture infectious doses per 100 µl, which was combined with an equal volume of diluted saliva (100 µl). After 1-hour incubation, the mixture was added to the wells with Vero cells. These plates with saliva diluted from 1:2 to 1:32 were incubated at 37°C with 5% CO2, and CPEs were scored at 24, 48, and 72 hours. The neutralization endpoint, defined as the most dilute saliva preventing CPE (curling of cells and disruption of the cell sheet layer), was used as an index of virus inhibition. In each assay, control wells were included, consisting of monolayers of Vero cells with either HSV-1 only or straight media.

Herpes-Specific Antibody
Specific antibody against HSV-1 (HSV-1–sIgA) in the saliva was determined by enzyme-linked immunosorbent assay. Briefly, microtiter plates were coated with HSV-1 (inactivated strain F, American Type Culture Collection; Wampole Laboratories, Cranbury, NJ), which served to bind HSV-1 antibody in saliva, and the bound complex reacted with goat antihuman sIgA. After addition of alkaline phosphatase substrate (Sigma, St. Louis, MO), the color reaction was stopped at 30 minutes with sodium hydroxide and then read with a Dynatech plate reader (Dynatech Laboratories, Chantilly, VA) at 405 nm.

Total Antibody
Total immunoglobulin A (IgA) levels were also quantified by enzyme-linked immunosorbent assay. Briefly, microtiter plates (Costar, Coring, NY) were coated overnight with 10 µg/ml monoclonal antihuman IgA (Sigma). Saliva samples diluted 1:5000 were tested in duplicate. After a 2-hour incubation, the plates were washed three times, and goat antihuman IgA alkaline phosphatase antibody was added. After a 2-hour incubation and a wash, Fast Soluble Alkaline phosphatase substrate (p-nitrophenyl phosphate; Sigma) was added. This reaction was stopped at 30 minutes, and the developing color was quantified with a Dynatech plate reader. Total sIgA concentrations were calibrated with respect to a standard curve generated with human sIgA purified from colostrum (Sigma).

Statistical Analyses
The three groups of women (nonabused, physically abused, and psychologically abused) were compared with respect to age, score of depression, anxiety, and PTSD using one-way analysis of variance (ANOVA). The level of education, prevalence of childhood abuse, adulthood victimization, and diagnoses of PTSD were compared by using Pearson {chi}2 tests. Volume of saliva and salivary flow rate were assessed by two-way ANOVA, considering time (morning, evening), day (day 1, day 2), and group as factors. Immune measures were compared with two-way ANOVA, considering the 2 days of specimen collection as a repeated measure. Post hoc comparisons were conducted with the Scheffé test. Correlations between the immune measures were tested with the Spearman and Pearson rank correlation coefficient. To determine the effect of abuse (childhood abuse, IPV, adulthood victimization) on immune measures after controlling for the variables age, smoking, and pharmacological treatment, hierarchical multiple regression analyses were performed entering step 1, control variables; and step 2, incidence of abuse. To test the hypothesis of the mediating effect of mental health status, additional regression analyses were performed entering step 1, control variables; step 2, incidence of abuse; and step 3, mental health status. The level of significance was set at .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
One hundred eleven women participated in this study. They were distributed into three groups: nonabused (N = 37), psychologically abused (N = 27), and physically abused (N = 47). There were no differences between groups in age (ANOVA, F[2,110] = 1.9; NS) or educational level ({chi}2[12, N = 111] = 8.4; NS; Table 1). Nearly all of the nonabused women (97.3%) had been cohabiting with their partners for the previous year and were still residing with them at the time of the saliva collection. The previous and current cohabitation figures for the psychologically abused and physically abused women were 88.9%, 70.4%, 89.4%, and 59.6%, respectively.


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  		TABLE 1. Characteristics of Women Nonabused, Psychologically Abused, and Physically Abused (%) by Their Intimate Male Partners
 
Violence Perpetrated by the Intimate Male Partner
All women (100%) who were subjected to physical violence (the physically abused group) also suffered from psychological abuse by their partners. Furthermore, 34% of the physically abused and 7.4% of the psychologically abused women were also sexually abused.

Most women in the physically abused group experienced violence by the batterer during the 12 months before their participation in the study: 87.2% experienced physical abuse, 95.7% psychological abuse, and 15.2% sexual abuse. Similarly, 88% of the psychologically abused women experienced recurrent psychological abuse during the previous year, with 4.2% also sexually abused.

Lifetime History of Victimization
Childhood Abuse
There was a history of childhood abuse in all three groups. Whereas 27%, 24.3%, and 13.5% of the nonabused women had a childhood history of physical, psychological, and sexual abuse, respectively, these figures were higher for the psychologically abused (55.6%, 44.4%, and 33.3%) and physically abused groups (42.6%, 40.4%, and 34%). These differences were not statistically significant between the groups for childhood psychological abuse ({chi}2[2, N = 111] = 3.4; NS), but the differences did approach statistical significance for physical ({chi}2[2, N = 111] = 5.4; p = .07) and sexual abuse ({chi}2[2, N = 111] = 5.1; p = .07). The incidence of physical and sexual childhood abuse was higher than expected in the two abused groups but not in the nonabused group.

Adulthood Victimization
Violence perpetrated toward these women by people other than the intimate male partner during adulthood occurred in all three groups, with no significant differences between groups in physical ({chi}2[2, N = 111] = 1.4; NS), psychological ({chi}2[2, N = 111] = 3.1; NS), or sexual violence ({chi}2[2, N = 111] = 2.5; NS).

Current Mental Health Status
There were highly significant differences between groups in the severity of self-rated depression (F[2,110] = 15.7; p < .001), state anxiety (F[2,110] = 15.7; p < .001), and the occurrence of PTSD diagnoses ({chi}2[2, N = 111] = 11.9; p < .005; Table 2). Both the physically and psychologically abused groups were more depressed and anxious and had a higher incidence of PTSD than the nonabused group, but there were no significant differences between the two abused groups.


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  		TABLE 2. Mean (± SD) Severity of Self-Rated Depression (BDI), State Anxiety (STAI), and Posttraumatic Stress Disorder (PTSD) in Women Nonabused, Psychologically Abused, and Physically Abused by Their Intimate Male Partners
 
Salivary Measures
There were no significant differences across the three groups in either the volume of saliva provided by the women (F[2,70] = 0.2; NS) or the salivary flow rate (F[2,69] = 0.2; NS), or in the morning or evening collection periods. On average, women provided a specimen volume of 6.2 ml, and the saliva drool was collected at the rate of 0.58 ml/min. Furthermore, there was no group by day interaction for either the volume (F[2,68] = 0.6; NS) or the flow rate (F[2,67] = 0.7; NS), indicating that these parameters of the saliva collection did not differ across the 2 days on which women provided specimens.

However, the capacity of the saliva to neutralize HSV-1 did differ significantly across the three groups (F[2,110] = 19.5; p < .001). Post hoc comparisons indicated that the physically abused group had the lowest bioactivity, significantly below the other two groups (p < .001), with the psychologically abused group intermediate (Figure 1). The values were similar across the 2 collection days and were highly correlated (r = 0.68; p < .01). Nevertheless, the magnitude of the differences between nonabused and abused women was slightly greater on the first day of collection, resulting in a significant group by day interaction (F[2,108] = 3.2; p < .05). The extent of the IPV effect on bioactivity was particularly striking when considered in terms of the percentage of women who evinced no neutralization activity at all. Although 83.8% of the nonabused women showed at least some virus neutralization, only 25.5% of the physically abused and 63% of the psychologically abused women showed antiviral activity. These differences were statistically significant between the groups ({chi}2[2, N = 111] = 28.7; p < .001). The percentage of nonabused women who evinced neutralization activity was higher than expected, whereas it was lower in the physically abused women. However, in the psychologically abused women, it was slightly higher than expected.



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  		Figure 1. Mean (±SE) dilution of saliva capable of neutralizing herpes simplex virus type 1 in women nonabused, psychologically abused, and physically abused by their intimate male partners. ***Differs from nonabused and psychologically abused women; p < .001.

 
The levels of HSV-1–sIgA also differed significantly among the three groups (F[2,110] = 3.7; p < .03), with the lowest titers seen in the physically abused women (Figure 2). Post hoc comparison showed that the significance was driven primarily by the discrepancy between physically abused and psychologically abused women—the latter had higher HSV-1–sIgA levels (p < .05)—rather than by the difference from the nonabused women. In contrast, total IgA did not significantly differentiate the three groups (F[2,110] = 1.3; NS). Attempts to correlate HSV-1–sIgA values with the amount of virus neutralization did not indicate that they were directly associated (r = 0.03; NS). Similarly, the overall levels of total IgA were not correlated with virus neutralization (r = 0.06; NS). In fact, HSV-1–sIgA was negatively correlated with total IgA values (r = –0.19; p < .05), indicating that the differences in virus neutralization and HSV-1–sIgA were not mediated by differences in total antibody in the mouth.



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  		Figure 2. Mean (±SE) herpes simplex virus type 1 specific antibody (HSV-1–sIgA) in women nonabused, psychologically abused, and physically abused by their intimate male partners. *Differs from physically abused women; p < .05.

 
Correlations Between Mental Health Status and Immune Function
Bivariate correlations indicated that there was an inverse association between virus neutralization and severity of depression (r = –0.27; p < .01), state anxiety (r = –0.27; p < .01), and PTSD (r = –0.28; p < .01). On the contrary, total IgA had a positive association with severity of depression (r = 0.28; p < .01) and PTSD (r = 0.19; p < .05). There were no significant correlations between HSV-1–sIgA and depression, anxiety, or PTSD.

Association Between Abuse, Psychological Distress, and Immunity
Hierarchical multiple regression analyses were conducted to investigate the relationships among childhood abuse, adulthood victimization, and IPV and the two measures of herpes-related immunity (virus neutralization and HSV-1–sIgA). The analyses showed that the control variables (age, smoking, and pharmacological treatment) did not predict the differences in virus neutralization (F[7,101] = 0.4; R2 = 0.03; NS). Instead, the experience of abuse was a significant predictor of the level of neutralization (F[9,92] = 3.4; R2 = 0.24; p < .001), with physical IPV (ß = –0.3; t = –2.6; p < .02) and psychological IPV (ß = –0.3; t = –2.4; p < .02) the primary factors. Additional regression analyses showed that neither the control variables (F[7,101] = 1.2; R2 = 0.08; NS) nor the experience of abuse (F[9,92] = 1.6; R2 = 0.1; NS) predicted the differences in HSV-1–sIgA. Only physical IPV (ß = –0.3; t = –2.1; p < .05) and childhood sexual abuse (ß = 0.3; t = 2.3; p < .03) were revealed as predictors.

To determine the possible mediational effect of the mental health status, first a regression analysis indicated that the experience of abuse predicted the differences in mental health status (F[9,92] = 5.8; R2 = 0.3; p < .001), with psychological IPV (ß = 0.6; t = 5.2; p < .001) as the primary factor. However, mental health status did not predict virus neutralization (F[1,91] = 1.9; R2 = 0.01; NS) or HSV-1–sIgA (F[1,91] = 0.01; R2 = 0.001; NS). Therefore, the mediational effect was not confirmed.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The results confirm the primary hypothesis that IPV has a negative effect on immune responses related to HSV-1 infection. The reduction in the virus neutralizing capacity of saliva obtained from the abused women was quite profound, especially when one considers the many abused women who evinced a total absence of antiviral activity. Compared with only 16% of nonabused control women who showed no virus neutralization in this salivary assay, 75% of the physically abused and 37% of the psychologically abused women evinced none. In addition, based on this neutralization measure, women who had been physically abused were affected more than those who had received only psychological abuse.

Our initial expectation was that these findings would be explained by a parallel decline in the levels of secretory antibody in the saliva. Although there was a lower HSV-1–specific IgA in the physically abused women, it did not correlate directly with the neutralization of live virus. We believe, therefore, that the reduction in neutralizing activity was probably mediated more by other antiviral factors, perhaps in addition to HSV-1–specific IgA. For example, it is known that saliva contains potent, small-molecular-weight proteins, such as the cystatins and proline-rich proteins, which can also inhibit HSV-1 (51). In addition, recent studies have demonstrated that stress can affect other antimicrobial properties of saliva, especially related to the adherence and growth of bacteria (52,53). Because stressful events can alter other aspects of saliva, including viscosity and quantity, we analyzed whether there were any differences in saliva volume and flow rate. No significant differences were found between groups, indicating that neither of these factors accounted for the effect of IPV on viral neutralization activity. Moreover, the influence of any idiosyncratic aspect of specimen collection would have been minimized by our preparatory step of pooling two samples from each day and then replicating the results on a second day. Neutralization activity was remarkably consistent within a person, despite the fact that the days of collection were scheduled 2 weeks apart.

Finally, it should be reiterated that there were no overall group differences in the level of total IgA. This finding was surprising because of the large literature describing how stress can reduce IgA levels in the mouth, but it should be noted that many of those studies involved acute stress situations, which also resulted in changes in saliva flow rates (54). Our collection and assay procedures would have minimized any effects driven by saliva volume or flow rate. With regard to differences in HSV-1–sIgA, it is noteworthy that the physically abused women showed lower levels of both neutralization activity and HSV-1–sIgA, whereas low neutralization in the psychologically abused women was accompanied by HSV-1–sIgA levels that were actually higher than those of controls. The latter profile may reflect the emergence of a humoral response to viral activation analogous to many reports that the antibody to EBV rises in people during times of stress (55). With regard to the specific reason for measuring sIgA in saliva, it should be noted that IgA is the predominant class of antibody in the mouth, accounting for approximately 80% of the total antibody present. The secretory form (sIgA) that is excreted on the mucosal epithelia is a more complex molecule than IgA in blood, composed of a IgA dimer and a secretory component, which enhances its stability and resistance to proteolytic enzymes. Although IgA has a short half-life (only 5–6 days), and there is tremendous turnover in saliva each day (approximately 100–200 mg/day is secreted), once an immunological memory is established, sIgA specific to an antigen may be excreted for many years (eg, for as long as 5 years after an oral polio vaccination; 54).

The overall finding that HSV-1 immunity is responsive to IPV is consistent with previous studies on stress and other types of herpes viruses. A seminal study in behavioral medicine by Kasl et al. (56) documented that students experiencing the stress of entering a military academy were more likely to be infected with EBV, and that those who succumbed to mononucleosis were more likely to have been academically challenged by the curriculum. More recent studies on medical students during examination periods and on women during stressful divorces found that they showed an increase in antibody titer to EBV in their blood (57,58). These authors interpreted the higher antibody as indicating a failure of cellular immunity to contain the virus, resulting in the initiation of a humoral immune response (ie, antibody production). Furthermore, Glaser et al. (58) have hypothesized that it would not be necessary for the virus to become fully activated, because even producing partial viral proteins would be sufficient to induce an immune response. Our study evaluated immunity only in the oral compartment, and suggests that the stress induced by IPV may impair factors involved in viral containment on the mucosal surface. Detection of an increased occurrence of oral lesions would validate the clinical significance of the current observation. However, others have already found that overt measures of herpes symptoms are sometimes challenging to detect because of the variable time course with respect to the stressful event (36,42,56).

Our evaluation of the psychological status of the abused women confirmed the prevailing view that IPV should be considered a major stressful life event that causes tremendous emotional disturbance. Both physically and psychologically abused women reported depression and anxiety and had a high diagnosis level of PTSD. Each of these psychological states was moderately correlated with the HSV-1 neutralization measure, but it was not possible to prove in the overall analytic model that the effect of IPV on immunity was driven by the degree of emotional disturbance. Designation of specific mediators is often challenging because of the co-occurrence of many negative processes. IPV was often accompanied by a significant risk for other types of abuse such as childhood maltreatment. In addition, any study of this nature must accept some methodological limitations because of ethical concerns about reasonable access to women at this extremely difficult time in their lives. We believe that our research design and methodology reflected a fair balance given the need to also provide compassionate assistance to those seeking help at our women’s centers.

In summary, this study has demonstrated that a noninvasive specimen collection approach and a novel immune outcome measure can be used to investigate the serious health-related problems evident in women who experience IPV. Documenting that this type of social stress has a sustained physiological effect ideally will help to highlight the significance of its health cost. We already know that many other immune-related processes are compromised during stressful situations, especially those related to one’s capacity to respond to infectious pathogens (58–60). It is likely that women victims of IPV are also at increased risk for other types of infections, and perhaps may be more likely to succumb to certain immune and inflammatory disorders as they age, especially if they experience abuse over a prolonged period.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
M.M. was supported by the Institute of the Woman, Ministry of Work and Social Affairs (ref:53/98), FEDER, and the Ministry of Science and Technology (ref:BSO2001–3134, and PGC2000–2354-E). C.L.C. received support from the National Institute of Health and the University of Wisconsin Graduate School.

Special thanks are given to Ms. Alla Slukvina for assistance with the immune assays, to Ms. Miriam Phillips for assistance with editing, and to Dr. Vicente Gonzalez-Roma for statistical help. Acknowledgments are also given to the Conselleria of Social Welfare and the 24-hour centers for helping women of the Valencian Community of Spain for their assistance in contacting the battered women.

Received for publication April 1, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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