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Psychosomatic Medicine 67:64-71 (2005)
© 2005 American Psychosomatic Society

ORIGINAL ARTICLES

Mothers With Breast Cancer and Their Adult Daughters: The Relationship Between Mothers’ Reaction to Breast Cancer and Their Daughters’ Emotional and Neuroimmune Status

Miri Cohen, PhD and Shimon Pollack, MD

From the Faculty of Welfare and Health Studies, Haifa University, Mount Carmel, Haifa, Israel.

Address correspondence and reprint requests to Miri Cohen, PhD, Faculty of Welfare and Health Studies, Haifa University, Mount Carmel, Haifa, Israel. E-mail: cohenm{at}research.haifa.ac.il


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Objectives: The objectives of this study were to assess the associations between psychologic distress of patients with breast cancer and of their adult daughters; and to assess the associations between mothers’ psychologic distress and daughters’ psychologic distress, stress hormone levels, natural cytotoxic activity (NCA), and Th1 cytokine secretion.

Methods: Eighty mothers with breast cancer and 80 adult daughters participated in the study. They completed the Symptom Check List (SCL-90R) questionnaire. In addition, daughters completed a set of questions on their health status and habits and on the effects of their mothers’ disease on their own lives. Thirty milliliters of heparinized venous blood and a first early-morning urine sample were collected from daughters between 8:00 and 9:00am. Spontaneous and interleukin-2 (IL-2)-induced NCA, in vitro IL-2 and IL-12 secretion, and levels of plasma cortisol and urinary catecholamines were tested in daughters. Forty-seven healthy women, age- and education- matched to daughters, completed the psychologic, immunologic, and hormonal tests, and served as a control group.

Results: Psychologic distress of mothers and daughters was highly correlated. However, mothers experienced a higher level of distress than daughters. Mothers with advanced disease and their daughters were more distressed than mothers with primary disease and their daughters. Daughters’ distress was also related to their subjective caregiving burden and the frequency of meetings with mothers. Higher distressed daughters had lower IL-2-induced NCA and decreased in vitro IL-2 and IL-12 secretion. Norepinephrine secretion level mediated the relationship between daughters’ level of distress and their immune functions. Cortisol mediated only the relationship between daughters’ distress and IL-2 secretion.

Conclusions: This initial study shows that the psychologic distress of mothers with breast cancer and that of their adult daughters are similar. Stress hormone secretions and immune functions of daughters are related to both their own and their mothers’ psychologic distress.

Key Words: breast cancer • mothers and daughters • immune surveillance • neuroendocrine status • psychologic distress

Abbreviations: GSI= Global Severity Index; IL-2 = interleukin 2; IL-12 = interleukin 12; NCA = natural cytotoxic activity; SCL = symptom checklist; SD = standard deviation.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Thelives of family members are intertwined (1) and life-course transitions experienced by one member of a family have an effect on the others, including adult offspring (1,2).

Cancer in a parent is one of the major events that affect the psychologic state of the entire family (3–5). Previous studies highlighted the significant consequences of cancer on other family members, who often experience fears, anxieties, and depression that mirror those of the patient in their nature and in the level of distress (6–10). Gilbar and Refaeli found significant positive correlations between symptoms of psychologic distress in adult patients with cancer and their parents (7). Lewis reported that higher levels of depression in mothers were associated with more emotional and adjustment problems in their young children (8). Also, several studies found that the recurrence of cancer was related to higher psychologic distress in patients (11–13) and in their family members (9,14–16).

Psychological Distress and Immune Functions in Daughters of Patients With Breast Cancer
Most studies on the effect of cancer on the family emphasized the responses of the spouse or of young/adolescent offspring to their mother’s disease (2,3,9,10,14). Within the familial system, mother–daughter relationships tend to be the strongest and most enduring of filial connections (17,18), but also the most emotionally loaded and often conflictual (19). In fact, previous research has found that mothers and adult daughters claim to experience greater tension as well as greater intimacy in their relationship (20). Hence, mothers’ illness, particularly a life-threatening illness, has a distinctive effect on their daughters (21). This effect is especially strong for daughters of patients with breast cancer, because breast cancer raises issues concerning fear of mothers’ death (10,22) as well as fears concerning their own susceptibility to develop breast cancer (23). Also, mothers’ illness often disrupts daughters’ everyday lives and plans for the future (23).

Daughters are the family members who are most likely to step into a caregiving role, especially when the mother is the one who needs care (24). Caregiving for older and/or sick parents is often a stressful experience and it has a negative effect on caregivers’ physical and psychologic well-being (reviewed in (25,26)). Previous studies had identified several factors that mediate the effect of caregiving on psychologic and physiological consequences of the caregivers such as the subjective perception of burden, frequency of encounters, kind and amount of assistance, and degree of disruption in the caregiver’s life (26). Also, caring for a psychologically distressed parent may intensify the feelings of burden (16). It has been already suggested that people who are depressed induce depression and feelings of guilt in others who are in contact with them (27). They also impose more caregiving needs on their family members (28). The more intensive the contact, the stronger its impact (27).

In addition, most of the studies that examined the psychologic state of women who had a first-degree relative with breast cancer have concentrated on the impact of the threat of being at high risk for breast cancer (eg, (29,30)). However, these studies overlooked the effect of factors related to the relative’s disease such as stage of disease, time since diagnosis, and her psychologic reaction.

We have previously reported that daughters of patients with breast cancer presented with significantly higher psychologic distress in comparison to age- and education-matched control women (31). In addition, we examined the relationship between their distress and immune surveillance functions. Natural cytotoxic activity (NCA) against various target cells, both NK-resistant and NK-sensitive, was significantly lower in daughters and much less augmented by in vitro preincubation with IL-2 or IL-12 than in controls. Also, in vitro IL-2 and IL-12 secretion was lower in daughters compared with controls. Blood levels of cortisol and urinary catecholamines in daughters were higher than in controls. NCA and in vitro cytokine secretion were positively correlated with the degree of psychologic distress and the level of blood cortisol and urinary norepinephrine (31).

These results support previous studies reporting that psychologic distress in reaction to various long-term stressful life events (such as caring for a spouse with Alzheimer (32), bereavement (33), exposure to hurricane (34)) is related to a decrease in immune cytotoxic functions. There is also empiric evidence that this association is mediated through secretion of stress hormones such as cortisol, catecholamines, and prolactin (reviewed in (35–37)). To date, however, no data on the relationship between mothers’ emotional state and daughters’ immune surveillance functions have been reported.

Our present study is an extension of previously published data (31) and is an effort to examine factors that contribute to increased psychologic distress in daughters of mothers with breast cancer, and which in turn may influence their neuroendocrine and immune functions. Thus, our aim in this present study was twofold: to assess the relationship between psychologic distress of mothers with breast cancer and psychologic distress of their adult daughters; and to assess the relationship between mothers’ and daughters’ psychologic distress and the hormonal and immune functions of daughters. We hypothesized that: 1) mothers’ psychologic distress will be positively related to daughters’ psychologic distress; 2) mothers’ cancer stage (primary or advanced) will be related to their own and to their daughters’ psychologic distress, both directly and indirectly (through its effect on mothers’ psychologic distress); 3 the effect of mothers’ illness on daughters’ lives (ie, frequency of meetings, amount of caregiving and its subjective burden, and degree of disruption in daughters’ lives) will mediate the effect of mothers’ psychologic distress on daughters’ distress; and 4) cortisol, epinephrine, and norepinephrine levels will be associated with both mothers’ and daughters’ psychologic distress and with daughters’ immune functions.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Subjects
Eighty patients with breast cancer and 80 daughters participated in the study: 39 patients had a primary and localized breast cancer and 41 patients had advanced (recurrent or metastatic) breast cancer. Both primary and advanced breast cancer were diagnosed 1 year before the patients joined the study; this timing was adopted to eliminate the effect of acute stress related to the early period after cancer diagnosis. Also, 47 women, age- and education-matched to the daughters, served as a control group in the study. The inclusion criteria for both mother–daughter dyads and controls were fluency in speaking Hebrew, absence of previous or current psychiatric illness, and age range 20 to 45 years of daughters and controls. Mother–daughter dyads and controls were excluded if the daughter or control were pregnant or on medications or had a history of cancer, benign tumor, or a chronic disease. Daughters and controls who had an acute viral infection or allergic reaction were studied 3 weeks or more after remission of symptoms.

Procedure
This research was part of a large study aimed at assessing of coping with stress and immune surveillance functions in daughters of patients with breast cancer. Patients were recruited from three oncology units in Northern Israel. A letter explaining the aim and the procedure of the study was sent to the patients. After a short time, a phone call was made to each patient, asking for her own and her daughter’s agreement to participate in the study. One hundred ninety-one daughters were approached, of whom 38 (19.9%) refused to participate; 56 (29.3%) could not participate for practical reasons (distance, work schedule, and so on), and 17 (8.9%) were excluded because of medical problems. Thus, we were left with 80 (41.9%) daughters. Controls were recruited through advertisements at medical centers, the Faculty of Medicine, and local newspapers. They were matched to daughters by age and education. Informed consent was obtained from all the participants, and they were also asked to complete the study questionnaires. In addition, 30 mL of heparinized blood was drawn from fasting daughters or controls between 8:00 and 9:00am for the measurement of immune variables and of plasma cortisol, and first-morning urine samples were tested for catecholamine levels. Blood and urine samples were collected either at the immunologic lab or outpatient clinic by the same physician and under the same conditions. All immune and hormonal tests were performed in the immunologic lab in parallel on daughters and controls. The study was approved by the Hospital Ethics Committee.

Reagents and Cell Lines
Reagents and cell lines—RPMI-1640, fetal calf serum (FCS), penicillin-streptomycin, trypsin, EDTA,l-glutamine, nonessential amino acid solution (NEAA), and sodium pyruvate—were all purchased from Biological Industries (Beit Ha’emek, Israel). Phytohemagglutinin (PHA) and lipopolysaccharide (LPS) from Escherichia coli were purchased from Sigma (St. Louis, MO). Chromium-51 (51Cr) was obtained from Amersham (Buckinghamshire, UK). Recombinant human interleukin-2 (rhIL-2) was purchased from R&D (Minneapolis, MN). Enzyme-linked immunosorbent assay (ELISA) kits for human IL-2 were acquired from R&D. Human breast cancer MCF7 cell lines were maintained in cell culture medium RPMI-1640 supplemented with 10% FCS at a concentration of 106 cells/mL in continuous suspension cultures.

Immunologic and Hormonal Methods
Spontaneous and Cytokine-Augmented Natural Cytotoxic Activity
PBMC were incubated with rhIL-2 (1000 U/mL) or rhIL-12 (100 pM) or in culture medium alone, for 18 hours, at 37° (38), washed and then incubated with51Cr-labeled NCA-resistant (MCF7) target cells for 4 hours in effector:target ratios of 10:1, 5:1, and 2.5:1, as previously described (39). NCA is presented as the number of lytic units in 107 effector cells (1 LU is the number of effector cells that lyse 20% of target cells). LU was calculated as previously described in detail (40) with the aid of an appropriate computer program (a gift from Prof. T. Whiteside, University of Pittsburgh School of Medicine, Pittsburgh, PA).

Cytokine Secretion
IL-2 and IL-12 levels were measured in supernatants of stimulated PBMC. For IL-2, 2 x 106 PBMC were incubated in RPMI-FCS culture medium with PHA (5 µg/mL) for 32 hours at 37°C (41). For IL-12, 5 x 106 plastic-adherent PBMC were incubated in 1 mL culture medium without FCS and stimulated with LPS (10 µg/mL) for 18 hours at 37°C. The assay for IL-12 recognizes the biologically active IL-12 heterodimer (p70) (42). Sensitivity threshold levels of ELISA kits (R&D) used for measuring cytokine concentration were 10 pg/mL for IL-2 and 0.5 pg/mL for IL-12.

Cortisol and Catecholamine Levels
Cortisol concentration in plasma was detected by Gamma Coat Cortisol Radioimmunoassay (DiaSorin, Stillwater, OR), as previously described (43). Catecholamine levels in urine were measured by high-pressure liquid chromatography (HPLC) with an electrochemical detector system (ESA Coulochem, Bedford, MA), as previously described (43).

Questionnaires
Demographic data were obtained through a questionnaire constructed for the purposes of this study. Medical data on cancer stage and history of treatment were obtained from medical files, with informed consent.

Symptoms Checklist Revised (SCL-90R) is composed of 90 items that represent nine categories of emotional symptoms, and it is suitable for emotional response to physical illness (44). Each item is scored on a 5-point scale ranging from 0 (none at all) to 5 (extreme). The questionnaire has been translated to Hebrew and used in studies across a wide spectrum of the population. The validity (construct and discriminating) and reliability of the Hebrew version were confirmed (45). Internal consistency ({alpha}) of the translated version ranged from 0.77 to 0.70 (45). Internal consistency ({alpha}) of the categories ranged from 0.64 to 0.88. A global severity index (GSI) was obtained by averaging the scores of the 90 items for each subject. Internal consistency ({alpha}) of the GSI was 0.96 for mothers and 0.95 for the daughters.

A health status and health habits questionnaire was constructed for the purpose of the present study and included parameters that may affect immune and hormonal functions (46) such as sleeping and diet habits, smoking and caffeine consumption, week of the menstruation cycle, as well as major stressful events in the last 3 years and an acute feeling of stress related to the blood drawing.

Effects of mothers’ disease on daughters’ lives was assessed by four different scales, composed for the present study: 1) Frequency of meetings with mothers was assessed by three questions: frequency of meetings for giving any kind of assistance to mother, frequency of meetings for spending time together, and frequency of family meetings with mother. Answers ranged from 1 (less than once in 2 weeks) to 4 (twice a week or more). Internal consistency ({alpha}) was 0.64. 2) Amount of caregiving scale consisted of four questions eliciting the frequency of assistance with washing and dressing, shopping and errands outside the home, housework, and escorting mother to medical and other appointments. Answers ranged from 1 (less than once in 2 weeks) to 4 (twice a week or more). {alpha} for the scale was 0.79. 3) Degree of subjective caregiving burden was assessed by asking the daughters to grade their subjective feeling of stress regarding their care of their mother in the previous 2 weeks, on a scale ranging from 1 (no stress at all) to 5 (extreme feeling of stress). 4) Degree of disruption in daughters’ lives by caregiving activities was again assessed by four questions addressing the degree of interruption in their work habits, in activities within the family, in leisure activities, and in activities for self-care. Answers ranged from 1 (not at all) to 4 (very much). {alpha} was 0.78. These questions were administered to the daughters only.

Statistical Methods
Descriptive statistics were used to examine the characteristics of the sample. Multivariate analysis of variance (MANOVA) was used to assess differences between the two groups of daughters in immune and hormonal variables followed by univariate ANOVA. Significant main effects were followed up by post hoc Scheffe test to identify differences between pairs of groups. ANOVA and t test were used when appropriate to measure differences in the other variables studied. Interactions among psychologic, immune, and hormonal variables were assessed by Pearson and Spearman (for correlation with stage of disease) analysis. A path analysis (seeFigure 1) was used to assess direct and indirect relation between stage of disease, mothers’ psychologic distress, effect of mothers’ disease on daughters’ lives, daughters’psychologic distress, and daughters’ hormonal and immune functions. Levels of significance are shown inTables 1 and 2. A probability level of 0.05 was accepted as significant.



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  		Figure 1. Path analysis of daughters’ immune and hormone functions, effects of mothers’ disease on daughters’ life (frequency of meetings and caregiving burden), mothers’ and daughters’ psychologic distress, and mothers’ stage of disease. The model was assessed by means of four serial multiple regressions. The last stage tested the full model, in which daughters’ NCA, IL-2 secretion, or IL-12 secretion were regressed on the foregoing variables. Numbers on arrows are standard regression coefficients; * p <.05. ** p <.01. {square}Mothers’ variables. {circ}Daughters’ variables. GSI = Global Severity Index; NCA = natural cytotoxic activity; NE = norepinephrine.

 

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  		TABLE 1. Effects of Mothers’ Disease on Daughters’ Lives

 


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  		TABLE 2. Correlation of Mothers’ Stage of Disease and Psychologic Distress With Daughters’ Psychologic, Hormone. and Immune Functions

 

   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 NOTES
 REFERENCES
 
Demographic Characteristics
Mean age of mothers was 61.4 ± 8.9 (standard deviation [SD]) years, whereas mean age of daughters was 31.7 ± 7.7 (SD). Seventy-nine percent of the mothers and 57.5% of the daughters were married; most of the unmarried mothers were widows, whereas most of the unmarried daughters had never been married. Mothers reported having 3.4 children on average, compared with 1.4 children on average for daughters. Mean years of education were 11.9 ± 4.9 (SD) for mothers and 14.4 ± 4.4 (SD) for their daughters. A total of 96.2% of the daughters but only 28.0% of mothers were employed. As expected, ANOVA revealed significant differences in most of the demographic variables as a result of age differences between the two generations of mothers and daughters.

Hormonal and Immune Variables of Daughters
As previously reported (31), daughters of mothers with advanced cancer exhibited impaired immune surveillance functions (MANOVA: F[5,74] = 3.19; p <.05). Significant differences were found for IL-2-induced NCA, in vitro IL-2 and IL-12 secretion, but not for spontaneous NCA. Levels of stress hormone (cortisol, epinephrine, and norepinephrine) secretion were higher in daughters of mothers with advanced cancer than in daughters of mothers with primary cancer (MANOVA: F[3,74] = 4.47; p <.01).

Also, health habits and health status variables that could affect endocrine or immune parameters of daughters were controlled by means of age- and education-matched controls. The daughters’ group did not differ from controls in the number of negative life events during the 3 years before the study: not in their smoking, diet, or sleep habits, and not in the status of menstrual cycle or the degree of stress associated with blood drawing (data not shown).

Psychologic Distress in Daughters and Their Mothers
The mean GSI score of mothers with primary disease was 0.64 ± 0.55 (SD) and 0.92 ± 0.39 (SD) for mothers with advanced disease. The mean GSI score for daughters of mothers with primary disease was 0.50 ± 0.37 (SD) and 0.86 ± 0.46 (SD) for daughters of mothers with advanced disease (F[3,156] = 7.15; p <.001). Post hoc Scheffe test indicated that the differences in GSI mean scores were significant for the two pairs of mothers and for the two pairs of daughters. The difference in GSI scores remained significant after exclusion of the somatization subscale, whose symptoms may overlap symptoms of the disease (F[3,156] = 5.08; p <.01). The GSI scores were higher than the norms for the healthy Israeli population (45).

Effects of Mothers’ Disease on Daughters’ Lives
Table 1 presents differences in effects of mothers’ disease on daughters of mothers with advanced disease or daughters of mothers with primary disease. Daughters of mothers with advanced disease met with their mothers more frequently. They also experienced significantly higher levels of subjective caregiving burden. The overall amount of caregiving was not significantly different in the two daughter groups (p >.05). However, daughters of mothers with advanced disease provided much more assistance in washing and dressing activities (t[78] = 2.07; p <.05). Concerning disruption of daughters’ daily lives, there was no significant difference between the two groups of daughters (p>.05). Approximately 70% of them experienced some amount of disruption in their daily lives as a result of mothers’ disease, whereas only 22% experienced major disruption.

Association of Mothers’ and Daughters’ Psychologic Distress With Daughters’ Immune and Hormonal Functions
Table 2 presents the correlation coefficients for variables entered into the path model. GSI scores of mothers and daughters were higher when mothers had advanced disease. Also, daughters’ higher GSI scores were related to higher norepinephrine levels and lower IL-2 and IL-12 secretion and NCA, but not to cortisol levels. More frequent meetings with mothers and higher subjective caregiving burden were associated with higher GSI scores, higher norepinephrine levels, lower NCA, and reduced IL-2 secretion, but were not significantly associated with level of cortisol and IL-12 secretion. Norepinephrine levels were associated with NCA, IL-2 and IL-12 secretion, whereas levels of cortisol were associated with IL-2 secretion only. Daughters in a more advanced week of menstrual cycle had significantly lower levels of cortisol and higher levels of norepinephrine.

Amount of caregiving and degree of disruption of life were associated with caregiving burden and frequency of meetings (r range: 0.29–0.36; p <.05) (data not shown) but were not associated with immune functions (ie, outcome variables). Also, urinary epinephrine levels were not significantly associated with the psychologic or immune variables. These variables were not entered into the path model.

Correlation coefficients for the relations of these variables with demographic variables were also calculated. Widowed and divorced mothers had higher GSI scores (r = 0.25; p <.05). No significant associations were revealed for the daughters’ demographic variables.

Testing Psychologic Distress Model of Mothers and Daughters
The hypotheses on the relations between mothers’ stage of disease, mothers’ and daughters’ psychologic distress, frequency of meetings, and subjective caregiving burden and their association with daughters’ hormone and immune functions were tested by path analysis. NCA, IL-2 and IL-12 secretion were the outcome variables. Variables that were not in significant correlation with the outcome variables were not entered into the model. The excluded variables were: daughters’ level of epinephrine secretion, demographic variables, disruption in daughters’ lives, and amount of caregiving activities. Also, daughters’ health habits were not significantly associated with hormone and immune functions except for week of menstrual cycle, which was entered into the model. The model was assessed by means of five serial multiple regressions, as previously described (47): 1) mothers’ GSI was regressed on stage of disease and daughters menstrual cycle (R2 = 0.06); 2) subjective caregiving burden and frequency of meetings with mother were regressed on mothers’ GSI scores and the two foregoing independent variables (R2 = 0.12 each); 3) daughters’ GSI scores were regressed on subjective caregiving burden and frequency of meetings with mother and the foregoing independent variables (R2 = 0.39); 4) levels of daughters’ norepinephrine (R2 = 0.25) and cortisol (R2 = 0.16) were each separately regressed on the foregoing variables; and 5) the last stage tested the full model, in which daughters’ NCA (R2 = 0.28, adjusted R2 = 21), IL-2 secretion (R2 = 0.32, adjusted R2 = 26), or IL-12 secretion (R2 = 0.29, adjusted R2 = 22) were each regressed on all the foregoing variables. All effect sizes (R2) were significant at p <.05.

The results of the path analysis show that NCA and cytokine secretion were lower in daughters with psychologic distress. High norepinephrine secretion and elevated cortisol levels might have mediated this effect. Also, mothers with higher psychologic distress had more distressed daughters. This effect was partially mediated by daughters’ perception of subjective caregiving burden. Mothers with advanced disease were psychologically more distressed. The effect of mothers’ stage of disease on daughters’ distress was not direct but was mediated indirectly through mothers’ distress and frequency of meetings. Mothers’ psychologic distress had an indirect effect on daughters’ endocrine and immune functions, mediated by daughters’ level of distress.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
NOTES
 REFERENCES
 
The results of the current study suggest that daughters of psychologically distressed mothers with breast cancer tend themselves to be more distressed despite the differences evidenced in the intensity of the psychologic distress in mothers and daughters. Daughters’ psychologic distress level was affected by caregiving variables (subjective burden and frequency of meetings). Our results also indicate an indirect association between mothers’ psychologic distress and their adult daughters’ psychologic, hormonal, and immune status.

The association found between mothers and daughters in their pattern of psychologic distress confirms our first hypothesis. It is also in accordance with previous studies, which showed a similarity of psychologic reaction in patients with cancer and in their family members (7,15,16,47). Other studies showed that young daughters of patients with female cancer were more distressed than other family members (10,22). However, the interrelationships of psychologic distress in dyads of mothers with breast cancer and their adult daughters have not, so far, been reported. The experience with cancer in a family is multifaceted with unique and shared experiences of the patient and of each family member (3). Mothers and daughters may be more likely to share some aspects of the experience such as fear of breast cancer, fear of dying from breast cancer, and fear of damage to body image and loss of functioning (48). These shared experiences may contribute to similarity in mothers’ and daughters’ level of distress. Another possible explanation could be that during the developmental process in the family, its members tend to develop similar emotional patterns and to react similarly to stressful life events (49). This effect was previously found to be especially strong for mother–daughter dyads (18,49).

According to our second hypothesis, and in support of previous results (9,13), mothers with advanced breast cancer and their adult daughters reported higher psychologic distress than mothers with localized breast cancer and their adult daughters. Psychologic distress of mothers was directly related to cancer stage, whereas psychologic distress of daughters was indirectly only associated with mothers’ cancer stage. In daughters, level of distress of mothers may have a more profound effect on the level of daughters’ distress than their mothers’ stage of disease. Also, studies demonstrated that neither the severity of illness nor the type of illness were related to caregivers’ distress (reviewed in (26)). Demographic, personal, and caregiving variables often have a more substantial effect on the psychologic and physical health outcomes of caregivers (26). For example, the frequency of meetings with mothers, which is one of those caregiving variables, was related to higher distress in daughters. Being with a sick mother may confront the daughter with the mother’s fears concerning the disease and hence contributes to the daughter’s greater psychologic distress. When meetings are less frequent, psychologic processes such as avoidance and distancing of the reality of the mother’s illness are promoted and may have a positive effect on the daughter’s emotional state. Another possible explanation can be that more meetings consume more of the daughter’s time and thus aggravate role conflict with her other obligations. Role conflict in caregivers has been found to have a major effect on their psychologic distress (50).

In accordance with the third hypothesis, the association between mothers’ and daughters’ level of psychologic distress was found to be partially mediated through higher subjective caregiving burden experienced by the daughters, as was found before (26). This indirect effect supports the findings that a distressed person affects family members through his or her depressed behavior (27,28,51) and also through the caregiving burden imposed on the family (52). The subjective caregiving burden of the daughters may originate from the caregiving activities necessitated by the disease itself (52) or may be a result of caring for a depressed person (51). Several studies have reported that a high caregiving burden was related to more emotional and health symptoms in caregivers (53,54).

In support of our fourth hypothesis, psychologic distress of daughters was found to be related both directly and indirectly to IL-2-induced NCA and to the in vitro secretion of IL-2 and IL-12. Some other studies also pointed to an association of decreased cytokine-induced NCA (32,55) or of IL-2 or interferon–gamma secretion (56–58) with psychologic distress. In the present study, these relationships were partially mediated by urinary norepinephrine levels, whereas plasma cortisol levels were related only to IL-2 secretion. Epinephrine levels were not associated with any immune or psychologic variables. It has been already reported that IL-2-induced NCA, as well as IL-2 and IL-12 secretion, were depressed by sustained in vivo exposure to high levels of stress hormone secretion (59,60), but the results concerning the effects of psychologic stress on neuroendocrine functions are inconsistent (43,61,62). Still, less stability in the relation between psychologic distress and epinephrine levels has been reported (63). Also, several studies found an association between chronic stress and norepinephrine, but not cortisol, levels (62). However, the inconsistency in the role of cortisol, epinephrine, or norepinephrine in mediating the relationship between psychologic distress and immune functions could have resulted from the methodologic shortcomings of our study. We used single morning blood and urine samples. A single sample can be affected by transient factors such as the time of awakening (64,65). Also, cortisol and catecholamines are subject to diurnal variation, rendering the single time measure less reliable (66). A mean of serial morning samples, or a 24-hour urine collection (67), could offer more reliable results, but these measures far exceeded the participants’ readiness to cooperate. Also, several leading studies in the psychoimmunology realm reported a single time design (eg, (32,68)). We attempted to control the problematic issues of a single sample by drawing blood or taking urine samples at the same time in the morning (69).

In line with previous reports (70,71), week of menstrual cycle was directly related to cortisol and norepinephrine levels and hence indirectly related to the immune outcomes. These findings demonstrate the multifactorial influences (environmental, behavioral, and individual physiological factors) on the hormone and immune functions, and the complexity of measuring connections between mind and body (46,72). Many other physiological parameters may have a potential influence on hormonal and immune functions such as medication intake, chronic and acute illness, pregnancy, or strict weight-reducing diet (46,72). They all were controlled by the exclusion from the study of daughters with one or more of these attributes. Also, health behaviors like smoking, caffeine intake, and physical activity were not associated with hormone and immune functions, which suggests that sufficient control of possible interfering variables was exercised in the study. However, in light of the complexity of the study model, and the many factors that can influence the psychologic, hormonal, and immune parameters (46,70,71), the possibility of other interfering variables that were not assessed in the present study such as psychosocial, demographic, or physiological cannot be ruled out.

Previous studies have indicated that demographic variables such as age, education, or marital status sometimes influence hormone and immune functions directly or indirectly through psychologic distress (73). However, daughters and controls in our study were all in the age range of 20 to 45, which does not have a prominent effect on hormonal or immune functions. Most of the subjects were at least high school graduates, and most of the unmarried ones were young and single, a status in keeping with the present social norms (74) and hence not related to higher psychologic distress. This may explain why the demographic variables were not in correlation with the outcome variables, and we could exclude them from the path model. On the other hand, our participants’ similar demographic characteristics limit the feasibility of generalizing the results to other populations.

Another major limitation of the study is the possibility of a sampling problem, considering that only 42% of the eligible individuals actually participated in the study. Although dropping out of the study was partially the result of technical problems, it may be that participants and nonparticipants differed on important variables measured in the study such as distress levels or caregiving burden; this may limit the generalizability of the findings.

In conclusion, the study shows that similarity exists in psychologic distress of mothers with breast cancer and their adult daughters. Moreover, not only are hormone and immune functions of daughters related to their own level of psychologic distress, but they are also indirectly related to mothers’ level of psychologic distress and to daughters’ caregiving burden. However, the mutual influences of mothers’ and daughters’ reactions to breast cancer in mothers should be further explored with a prospective design and larger samples. In addition, the present results point to the need to establish support or psychoeducational intervention groups for daughters providing care for mothers with breast cancer. These will help them to cope better with their own and with the effect of their mothers’ psychologic distress (75). These interventions should help to alleviate the level of psychologic distress, improve coping strategies, and even enhance immune functions of this population at risk.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
REFERENCES
 
Received for publication November 3, 2002; revision received August 30, 2004.

DOI:10.1097/01.psy.0000151746.36540.6e


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

  1. Minuchin S. Families and Family Therapy. London: Tavistock; 1974.
  2. Baider L, Kaufman B, Peretz T, Manor R, Ever-Hadani P, Kaplan De-Nour AK. Mutuality of fate: adaptation and psychological distress in cancer patients and their partners. In: Baider L, Cary CL, De-Nour AK, eds. Cancer and the Family. New York: Wiley; 1996:173–86.
  3. Cassileth B, Lusk, EJ, Strouse TB, Miller DS, Brown LL, Cross PA. A psychological analysis of cancer patients and their next-of-kin. Cancer 1985;55:72–6.[CrossRef][Medline]
  4. Leedham B, Meyerowitz BE. Responses to parental cancer: a clinical perspective. J Clin Psychol Med Settings 1999;6:441–64.[CrossRef]
  5. Northouse L. The impact of cancer in women on the family. Cancer Pract 1995;3:134–42.[Medline]
  6. Oberst M, James, RH. Going home: patient and spouse adjustment following cancer surgery. Top Clin Nurs 1985;7:46–57.[Medline]
  7. Gilbar O, Refaeli R. The relationship between adult cancer patients’ adjustment to the illness and that of their parents. Fam Syst Health 2000;18:5–17.
  8. Lewis FM. The impact of breast cancer on the family: Lessons learned from the children and adolescents. In: Baider L, Cary CL, De-Nour AK, eds. Cancer and the Family. New York; John Wiley; 1996:271–87.
  9. Gotay CC. The experience of cancer during early and advanced stages: the views of patients and their mates. Soc Sci Med 1984;17:605–13.[CrossRef]
  10. Compas BE, Worsham NL, Epping-Jordan JE, Grant KE, Mireault G, Howell DC, Malcarne VL. When Mom or Dad has cancer: markers of psychological distress in cancer patients, spouses, and children. Health Psychol 1994;13:507–15.[CrossRef][Medline]
  11. Cella DF, Mahon SM, Donovan MI. Cancer recurrence as a traumatic event. Behav Med 1990;6:15–22.
  12. Fulton C. The prevalence and detection of psychiatric morbidity in patients with metastatic breast cancer. Eur J Cancer Care (Engl) 1998;7:232–9.
  13. Pinder KL, Ramirez AJ, Black ME, Richards MA, Gregory WM, Rubens RD. Psychiatric disorder in patients with advanced breast cancer: prevalence and associated factors. Eur J Cancer 1993;29:524–7.[CrossRef]
  14. Northouse LL, Dorris G, Charron-Moore C. Factors affecting couples’ adjustment to recurrent breast cancer. Soc Sci Med 1995;41:69–76.
  15. Kurtz ME, Kurtz JC, Given CW, Given B. Relationship of caregiver reactions and depression to cancer patients’ symptoms, functional states and depression: a longitudinal view. Soc Sci Med 1995;40:837–46.
  16. Given CW, Given B, Osuch J, Kurtz ME. The influence of cancer patients’ symptoms and functional states on patients’ depression and family caregivers’ reaction and depression. Health Psychol 1993;12:277–85.[CrossRef][Medline]
  17. Katz R. Mothers and daughters—the tie that binds: early identification and the psychotherapy of women. In: Fenchel GH, ed. The Mother–Daughter Relationship: Echoes Through Time. Northvale, NJ: Jason Aronson; 1998:245–63.
  18. Rossi AS, Rossi PH. Of Human Bonding: Parent–Child Relations Across the Life Course. Hawthorne, NY: Aldine de Gruyter; 1990.
  19. Fingerman KL. Sources of tension in the aging mother and adult daughter relationship. Psychol Aging 1996;11:591–606.[CrossRef][Medline]
  20. Lehr U. The role of women in the family generation context. In: Garms-Homolova EHV, Schaeffer D, eds. Intergenerational Relationships. Göttingen, Germany: Hogrefe; 1984:125–32.
  21. Lee MB, Lester P, Rotheram-Borus MJ. The relationship between adjustment of mothers with HIV and their adolescent daughters. Clin Child Psychol Psychiatry 2002;7:71–84.
  22. Lichtman R, Taylor SE, Wood JV. Relations with children after breast cancer: the mother–daughter relationship at risk. J Psychosoc Oncol 1984;2:1–19.
  23. Wellisch D, Gritz E, Schain W, Wang H, Siau J. Psychological functioning of daughters of breast cancer patients. Part II: characterizing the distressed daughter of the breast cancer patient. Psychosomatics 1992;33:171–9.[Abstract/Free Full Text]
  24. Stone R, Cafferata GL, Sangl J. Caregivers of the frail elderly: a national profile. Gerontologist 1987;27:616–26.[Medline]
  25. Biegel DE, Sales E, Sculz R. Family caregiving in chronic illness: Alzheimer’s disease, cancer, heart disease, mental illness, and stroke. Thousand Oaks, CA: Sage Publications; 1991.
  26. Nijboer C, Tempelaar R, Sanderman R, Triemstra M, Spruijt RJ, Van Den Bos GA. Cancer and caregiving: the impact on the caregiver’s health. Psychooncology 1998;7:3–13.[CrossRef][Medline]
  27. Coyne JC. Depression and response to others. J Abnorm Psychol 1976;2:186–93.[CrossRef]
  28. Jacob M, Frank E, Kupfer DJ, Carpenter LL. Recurrent depression: an assessment of family burden and family attitudes. J Clin Psychiatry 1987;48:395–400.[Medline]
  29. Kash K, Holland J, Halper M, Miller D. Psychological distress and surveillance behaviors of women with a family history of breast cancer. J Nat Cancer Inst 1992;84:24–30.[Abstract/Free Full Text]
  30. Lerman C, Schwartz M. Adherence and psychological adjustment among women at high risk for breast cancer. Breast Cancer Res Treat 1993;28:145–55.[CrossRef][Medline]
  31. Cohen M, Klein E, Kuten A, Fried G, Zeidner O, Pollack S. Increased emotional distress in daughters of breast cancer patients associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of Th1 cytokines. Int J Cancer 2002;100:347–54.[CrossRef][Medline]
  32. Esterling BA, Kiecolt-Glaser JK, Bodnar JC, Glaser R. Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults. Health Psychol 1994;13:291–8.[CrossRef][Medline]
  33. Schleifer SJ, Keller SE, Camerino M, Thornton JC, Stein M. Suppression of lymphocyte stimulation following bereavement. JAMA 1983;250:374–7.[Abstract/Free Full Text]
  34. Ironson G, Wynings C, Schneiderman N, Baum A, Rodriguez M, Greenwood D, Benight C, Antoni M, LaPerriere A, Huang HS, Klimas N, Fletcher MA. Posttraumatic stress symptoms, intrusive thoughts, loss, and immune function after Hurricane Andrew. Psychosom Med 1997;59:128–41.[Abstract/Free Full Text]
  35. Madden K, Felten D. Experimental basis for neural-immune interactions. Physiol Rev 1995;75:77–106.[Free Full Text]
  36. Buckingham JC, Cowell A-M, Gillies GE, Herbison AE, Steel AH. The neuroendocrine system: anatomy, physiology and responses to stress. In: Buckingham JC, Gillies GE, Cowell A-M, eds. Stress, Stress Hormones and the Immune System. Chichester: Wiley; 1977:9–47.
  37. Yang EV, Glaser R. Stress-induced immunomodulation and the implications for health. Int Immunopharmacol 2002;2:315–24.[CrossRef][Medline]
  38. Wingren AG, Dahlenborg K, Bjorklund M, Hedlund G, Kalland T, Sjogren HO, Ljungdahl A, Oisson T, Ekre HP, Sansom D, Dohlsten M. Monocyte-regulated IFN-gamma production in human T cells involves CD2 signaling. J Immunol 1993;151:1328–36.[Abstract]
  39. Robinson E, Rubin D, Mekori T, Segal S, Pollack S. In vivo modulation of natural killer cell activity by tamoxifen in patients with bilateral primary breast cancer. Cancer Immunol Immunother 1993;37:209–12.
  40. Bryant J, Day R, Whiteside TL, Herberman RB. Calculation of lytic units for the expression of cell-mediated cytotoxicity. J Immunol Methods 1992;146:91–103.[CrossRef][Medline]
  41. Fairfax C, Borzy MS. Interleukin 2 production, proliferative response, and receptor expression by cord blood mononuclear cells. J Clin Lab Immunol 1988;27:63–7.[Medline]
  42. Rook A, Kubin M, Cassin M, Vonderheid EC, Vowels BR, Wolfe JT, Wolf SF, Singh A, Trinchieri G, Lessin SR. IL-12 reverses cytokine and immune abnormalities in Sezary syndrome. J Immunol 1995;154:1491–8.[Abstract]
  43. Richter S, Schurmeyer TH, Schedlowski M, Hadicke A, Tewes U, Schmidt RE, Wagner TO. Time kinetics of the endocrine response to acute psychological stress. Clin Endocrinol Metabolism 1996;81:1956–60.
  44. Derogatis L, Rickels K, Rock AF. The SCL-90 and the MMPI: a step in the validation of a new self-report scale. Br J Psychiatry 1976;128:280–9.[Abstract/Free Full Text]
  45. Florian V, Drory Y. Mental Health Inventory (MHI)—Psychometric properties and normative data in the Israeli population. Psychologia: Is J Psychol 1990;2:26–35.
  46. Kiecolt-Glaser JK, Glaser R. Psychoneuroimmunology: can psychological interventions modulate immunity? J Consult Clin Psychol 1992;60:569–75.[CrossRef][Medline]
  47. Ben-Zur H, Gilbar O, Lev S. Coping with breast cancer: patient, spouse, and dyad models. Psychosom Med 2001;63:32–9.[Abstract/Free Full Text]
  48. Tarkan, L. My Mother’s Breast: Daughters Face Their Mother’s Cancer. Dallas, TX: Taylor; 1999.
  49. Roberto LG. Transgenerational Family Therapies. New York: Guilford; 1992.
  50. Perlin LI, Mullan JT, Semple SJ, Skaff MS. Caregiving and the stress process: an overview of concepts and their measures. Gerontologist 1990;5:583–91.
  51. Benazon NC. Living with a depressed spouse. J Fam Psychol 2000;14:71–9.[CrossRef][Medline]
  52. Kessler RC, Mcleod JD, Wethington E. The costs of caring: a perspective on the relationship between sex and psychological distress. In: Sarason IG, Sarason BR, eds. Social Support: Theory, Research and Applications. Dordrecht, The Netherlands: Martinus Nijhoff; 1987:491–506.
  53. Kiecolt-Glaser J, Dura J, Speicher C, Trask O, Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med 1991;53:345–62.[Abstract/Free Full Text]
  54. Oberst M, Thomas SE, Gass KA, Ward SE. Caregiving demands and appraisal of stress among family caregivers. Cancer Nurs 1991;12:209–15.
  55. Andersen B, Farrar W, Golden-Kreutz D, Kutz L, MacCallum R, Courtney M, Glaser R. Stress and immune responses after surgical treatment for regional breast cancer. J Natl Cancer Inst 1998;90:30–6.[Abstract/Free Full Text]
  56. Glaser R, Kiecolt-Glaser JK, Malarkey WB, Sheridan JF. The influence of psychological stress on the immune response to vaccines. Ann NY Acad Sci 1998;840:649–55.[CrossRef][Medline]
  57. Bauer ME, Perks P, Wilcock GK, Lightman SL, Shanks N, Vedhara K. Chronic stress in caregivers of dementia patients is associated with reduced lymphocyte sensitivity to glucocorticoids. J Neuroimmunol 2000;103:84–92.[CrossRef][Medline]
  58. Glaser R, Rice J, Speicher CE, Stout JC, Kiecolt-Glaser JK. Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. Behav Neurosci 1986;100:675–8.[CrossRef][Medline]
  59. Elenkov I, Papanicolaou DA, Wilder RL, Chrousos GP. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians 1996;108:374–81.[Medline]
  60. Staurenghi AM, Masera RG, Prolo P, Griot G, Sartori ML, Ravizza L, Angeli A. Hypothalamic–pituitary–adrenal axis function, psychopathological traits, and natural killer (NK) cell activity in anorexia nervosa. Psychoneuroendocrinology 1977;22:575–90.
  61. Irwin M, Daniels M, Risch SC, Bloom E, Weiner H. Plasma cortisol and natural killer cell activity during bereavement. Biol Psychiatry 1988;24:173–8.[CrossRef][Medline]
  62. Mills P, Ziegler MG, Patterson T, Dimsdale JE, Hauger R, Irwin M, Grant IP. Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress. Psychosom Med 1997;59:251–6.[Abstract/Free Full Text]
  63. Cohen S, Hamrick N, Rodriguez MS, Feldman PJ, Rabin BS, Manuck SB. The stability of and intercorrelations among cardiovascular, immune, endocrine, and psychological reactivity. Ann Behav Med 2000;22:1–10.[Medline]
  64. Chick J. Alcohol dependence, anxiety and mood disorders. Curr Opin Psychiatry 1999;12:297–301.[CrossRef]
  65. Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus–pituitary–adrenal axis. Psychosom Med 1999;61:154–62.[Abstract/Free Full Text]
  66. Cowell AM, Buckingham JC, Gillies GE. In vivo and in vitro methods for assessing neuroendocrine functions. In: Buckingham JC, Gillies GE, Cowell A-M, eds. Stress, Stress Hormones and the Immune System. Chichester: Wiley; 1997:129–56.
  67. Zametkin AJ, Ernst M, Silver R. Laboratory and diagnostic testing in child and adolescent psychiatry: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1998;37:464–72.[CrossRef][Medline]
  68. Tjemsland L, Soreide JR, Matre R, Malt UF. Preoperative psychological variables predict immunological status in patients with operable breast cancer. Psychooncology 1997;6:311–20.[CrossRef][Medline]
  69. Ratliff-Crain J, Temoshok L, Kiecolt-Glaser J. Issues in psychoneuroimmunology research. Health Psychol 1989;8:747–52.[CrossRef][Medline]
  70. Agarwal SK, Shippy AM, Henninger EM, Marshall GD. Immune alterations in healthy females during a normal menstrual cycle. J Allergy Clin Immunol 1997;99:222–8.[CrossRef]
  71. Bouman A, Moes H, Meineman MJ, De Leij L, Faas MM. Cytokine production by NK-lymphocytes in follicular and luteal phase of the ovarian cycle in humans. Am J Reprod Immunol 2001;45:130–4.
  72. Cohen S, Herbert TB. Health psychology: psychological factors and physical disease from the perspective of human psychoneuroimmunology. An Rev Psychol 1996;47:113–42.
  73. Schleifer SJ, Keller SE, Bond RN, Cohen J, Stein M. Major depressive disorder and immunity: role of age, sex, severity, and hospitalization. Arch Gen Psychiatry 1989;46:81–7.[Abstract/Free Full Text]
  74. Beaujot R. The family and demographic change in Canada: economic and cultural interpretations and solutions. J Comp Fam Stud 1990;21:25.
  75. Wellisch D, Hoffman A, Goldman S, Hammerstein J, Klein K, Bell M. Depression and anxiety symptoms in women at high risk for breast cancer: pilot study of a group intervention. Am J Psychiatry 1999;156:1644–5.[Abstract/Free Full Text]



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