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Psychosomatic Medicine 66:92-103 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Cognitive Processing Among Mothers of Children Undergoing Bone Marrow/Stem Cell Transplantation

Katherine N. DuHamel, PhD, Sharon Manne, PhD, Nancy Nereo, PhD, Jamie Ostroff, PhD, Richard Martini, MD, Susan Parsons, MD, Sharon Williams, PhD, Laura Mee, PhD, Sandra Sexson, MD, Lisa Wu, MS, Gary Winkel, PhD, Farid Boulad, MD and William H. Redd, PhD

From the Program for Cancer Prevention and Control, Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York (K.N.D., N.N., L.W., G.W., W.H.R.); Fox Chase Cancer Center, Philadelphia, Pennsylvania (S.M.); Memorial Sloan-Kettering Cancer Center, New York, New York (J.O., F.B.); Children’s Memorial Hospital, Northwestern University Medical Center, Chicago, Illinois (R.M.); Dana Farber Cancer Institute, Boston, Massachusetts (S.P.); Packard Children’s Hospital, Palo Alto, California (S.W.); and Emory University Medical Center, Atlanta, Georgia (L.M., S.S.).

Katherine N. DuHamel, PhD, Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1130 New York, NY 10029-6574. Email: katherine.duhamel{at}mssm.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: This study investigated the role of cognitive processing in maternal adjustment to a life-threatening pediatric medical procedure (bone marrow/stem cell transplantation: BMT/SCT).

METHODS: Ninety-one mothers participated in structured interviews about their fears, intrusions, avoidance, and distress regarding their child’s BMT/SCT at two time points: during their child’s hospitalization and during his/her recovery. Structural equation modeling was used to determine the role of fears, intrusions, and avoidance in mothers’ distress.

RESULTS: Mothers’ fears played a primary role in their adjustment to their child’s transplantation. Intrusions mediated the relations of fears with distress at both time points. Mothers’ avoidance of thoughts, feelings, and reminders of their child’s illness during the child’s transplantation was associated with their distress three months later. The child’s risk for an unsuccessful transplantation outcome was not associated with mothers’ fears or distress during the child’s hospitalization, but was associated with mothers’ distress during the child’s posthospital course of recovery.

CONCLUSIONS: The results of this study indicate the critical role of mothers’ fears, intrusions, avoidance, and the child’s transplant risk in maternal distress and have treatment implications for reducing maternal distress during pediatric transplantation.

Key Words: cognitive processing, • pediatric, • bone marrow and stem cell transplantation, • cancer, • mothers.

Abbreviations: ALL = acute lymphoblastic leukemia;; AML = acute myeloid leukemia;; BAI = Beck anxiety inventory;; BDI = Beck depression inventory;; BMT/SCT = bone marrow/stem cell transplantation;; GvHD = graft vs. host disease;; IES = impact of events scale;; IESA = IES avoidance subscale;; IESI = IES intrusion subscale.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Mothers of children undergoing bone marrow/stem cell transplantation (BMT/SCT) must cope with having their child undergo a life-threatening procedure as well as having a child diagnosed with a serious disease. Although potentially curative, pediatric BMT/SCT is a grueling process that is associated with significant morbidity and mortality (1). Our prior research (eg, 2) and research by others (eg, 3) suggests that pediatric BMT/SCT is traumatic for mothers. Mothers may experience anxiety and depression, which can persist after the child’s transplantation (4, 5) . However, the patterns of maternal psychological reactions vary (6, 7).

Clinical researchers have argued that a key component to mothers’ adjustment to their child’s BMT/SCT is how they cognitively process this event. Studies of adjustment after traumatic events indicate that people engage in cognitive processing to integrate the event into their lives and cope with the fears evoked by it (8–12). If research supports the application of cognitive processing to mothers’ adjustment to their child’s BMT/SCT, this would extend our understanding of mothers’ adjustment and could inform interventions to reduce mothers’ anxiety and depression.

Cognitive processing models are based on the notion that traumatic events are not consistent with the person’s perception of the world as safe, and that they are appraised as threatening (9–12). Such appraisal results in the development of a Fear Network, which contains information about the objective severity of the event and perceptions about the event (eg, that it is threatening) (10, 12). In the case of pediatric BMT/SCT, mothers may try to reduce their Fear Network and integrate the event into their world view through accommodation (eg, a mother might come to view the world as a place where major events happen out of her control) and/or assimilation (eg, she might see the event as a call to alter her priorities and focus on her family and social relationships). According to recent cognitive processing models, activation and modification of the Fear Network results in immediately high levels of intrusions (intrusive thoughts and images). In contrast to other trauma coping models that view intrusions as symptoms of poor adaptation (13, 14), cognitive processing models maintain that intrusions are an indication that the person is working to integrate the event and their Fear Network into their world view (8, 9, 15). When cognitive processing is successful and integration occurs, intrusions dissipate along with the associated distress. However, when intrusions are avoided, cognitive processing does not occur, and high levels of distress follow. Support for the paradoxical effect of avoidance/suppression has been provided by Wegner et al. in a series of experiments with undergraduate students (16, 17). For example, those students who were initially instructed not to think about something such as a white bear expressed it more frequently later than subjects who initially expressed the thought.

Research with individuals coping with traumas other than cancer supports the role of cognitive processing variables, particularly appraisals of threat, intrusions, and avoidance, in the development of distress (9, 15). For example, with office workers exposed to a multiple shooting incident in their office building, Creamer et al. (15) found that both physical proximity to the shooting, and perception of life threat were associated with greater distress. Intrusions and avoidance were found to mediate the relations among the amount of exposure to the office shooting and distress, and the perception of life threat and distress. Creamer et al. also found that intrusions were followed by avoidance and that an alternative model proposed by Horowitz et al. (11, 13) in which avoidance was placed before intrusions was not supported by their data. In addition, initial high levels of intrusions were associated with less distress 10 months later.

Prior research has also provided some support for the application of cognitive processing models to adults undergoing cancer treatment. In a longitudinal study among individuals with cancer, Manne, Glassman, and DuHamel (19) found that late-stage cancer patients who consciously attempted to avoid thoughts and memories about cancer had higher levels of distress over time. Other cancer researchers have also found support for the negative impact of inhibition, social constraints, and/or avoidance in processing the cancer experience (20–22). In addition, emotional expressivity has been associated with less distress and has been found to moderate the relation of intrusions and distress (23, 24). As noted by these researchers, data suggest that barriers to processing, whether internal (avoidance) or external (social constraints), are associated with more distress.

The purpose of the current longitudinal study was to evaluate the application of a cognitive processing model to mothers’ symptoms of distress (ie, anxiety and depression) during the course of their child’s transplantation. We have previously examined the rates of anxiety and depression and found that most mothers do not have clinically significant levels of distress (20% to 36% of the mothers interviewed met criteria for a diagnosis of generalized anxiety disorder, panic disorder, or major depression) (25). We have also found that the number of mothers’ fears (a component of the Fear Network) was a predictor of depressive symptoms (25). However, we have not previously investigated the application of a multiple component model of cognitive processing to mothers’ distress. The focus of this study on the examination of a cognitive processing model distinguishes it from our prior research. Specifically, in this study we sought to explore the relation of the child’s medical indicators (such as risk for an unsuccessful transplantation), with the mothers’ Fear Network, the relation of Fear Network with intrusions, the relation of intrusions with avoidance, and the relation of avoidance with mothers’ distress during the course of her child’s BMT/SCT hospitalization and recovery. Figure 1 illustrates our conceptualization of mothers’ fears, intrusions, avoidance, and distress for the 2 assessment times of the study (ie, during the child’s transplantation hospitalization and approximately 3 months later). Six hypotheses were made. First, we proposed that the child’s pre-transplantation disease, the risk of the transplantation itself, and the child’s medical problems during the course of transplantation and recovery would be associated with the size of the mother’s Fear Network (eg, the intensity of the mother’s appraisal of threat and the potential for suffering). Second, we hypothesized that at each time of assessment, the larger the Fear Network, the more frequent the mothers’ intrusions. Third, at each assessment, the greater the mothers’ intrusions, the greater their avoidance. Fourth, at each assessment, the more mothers avoided thinking about their fears, the greater their concurrent distress. Fifth, although intrusions would be associated initially with concurrent distress, intrusions would facilitate processing of the event and be directly associated with a reduction in distress over time. Finally, the relation of intrusions and avoidance would be cyclical over time. Thus, initial reliance on avoidance was proposed to inhibit assimilation and accommodation and perpetuate intrusions and the need to continue processing fears. Overall, the relations among the model variables were proposed to be mediational. We predicted that at each time of assessment, intrusions would mediate the relation between fears and avoidance, that avoidance would mediate the relation between intrusions and distress, and that both intrusions and avoidance would mediate the relation between the mothers’ fear and distress. Mediation was also proposed across time such that mothers’ initial level of fear would be associated with their subsequent distress through its relations with intrusions and avoidance. This study afforded a unique opportunity to investigate prospectively cognitive processing during the course of a stressful life experience.



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  		Fig. 1. A proposed cognitive processing model of psychological distress at Time 1 and Time 2.

 

   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Participants
Participants were 91 mothers of children undergoing BMT/SCT. The present investigation used data from participants in a larger multi-site longitudinal study of maternal distress and coping after pediatric BMT/SCT and represents a subgroup from that study. (See references 25, 25a, 26, 26a for additional study results.) Potential participants were recruited at BMT/SCT units at 6 hospitals: Dana Farber Cancer Institute, Emory University Medical Center, Memorial Sloan-Kettering Cancer Center, Mount Sinai School of Medicine, Northwestern University Medical Center, and Stanford University Medical Center. Eligibility requirements for inclusion were: 1) mother was able to read and write English, 2) mother was the primary caretaker for the child undergoing BMT/SCT, 3) mother was older than 18, and 4) child undergoing BMT/SCT was 21 or younger. For the larger study, 208 mothers were eligible for study participation. Fifty-six of the 208 mothers (27%) declined participation and 152 (73%) consented to the study. The most common reasons cited for nonparticipation included being overwhelmed and study burden. Seven of the consenting mothers (5%) were unable or unwilling to complete the baseline assessments during the child’s BMT/SCT hospitalization. Of the 122 mothers eligible for this study (ie, those who would have completed both times of assessment), 11 mothers skipped the second interview, 8 dropped out of the study between the first and second assessment, and 12 had children who had passed away. The final sample for this study comprised 91 mothers. The mothers who participated in the first interview did not differ from those who refused to participate in the first interview with regard to their race/ethnicity [Caucasian vs. all others, {chi}2 (1,137)= 1.17, p =.28] or with regard to their child’s age at time of interview [participants’ child’s mean = 8.7 years vs. nonparticipants’ child’s mean = 10.35 years, t (1,139) = 1.62, p =.11], gender [{chi}2 (1,142)= 0.01, p = .93], type of BMT/SCT [autologous vs. allogeneic; {chi}2 (1,142)= 0.48, p =.49], or if the child’s disease was nonmalignant or malignant [{chi}2 (1,142)= 0.01, p = .93]. Differences across sites were not analyzed in this small sample study. Chi-square tests (using Fishers Exact Test) and a t test comparing participating mothers with those who dropped out of the study between the first and second assessment indicated no differences for the child’s gender, ethnicity, malignancy status, type of BMT/SCT, or age.

At Time 1, the participants’ children ranged in age from 9 months to 19 years, with a mean age of 8 years. On average, the children were 22 months postdiagnosis (M = 21.95 months, SD = 25.52 months) and the mothers were 37 years old (M = 37.85 years, SD = 7.30). Table 1 presents further descriptive information about the participants and their children, including the medical risk and medical course information. To describe and quantify regimen-related toxicity (eg, cardiac, CNS, GI) during the BMT/SCT hospitalization, the Bearman Toxicity Scale, a common clinical rating scale, was completed (27). Additional medical information was obtained from medical chart review and included: type of malignancy and type of transplant (eg, autologous vs. allogeneic). For allogeneic transplants, type of donor (related/unrelated, HLA match) and graft vs. host disease (GvHD; presence, grade) was obtained.


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  		TABLE 1. Sample Descriptive Information
 
Procedures
Eligible mothers of pediatric BMT/SCT patients were approached by a research assistant before the child’s BMT/SCT. After informed consent was obtained, participants completed questionnaires. Questionnaires were administered twice. Time 1 interviews were conducted fact-to-face. Time 2 interviews were conducted face-to-face or over the telephone, depending on the mothers’ preference and availability. Time 1 took place after the participant’s child was admitted to the inpatient unit for the transplant during the course of the child’s hospitalization. On average, the mothers completed this interview 3 days before the BMT/SCT infusion, a time corresponding to an acute phase of medical treatment characterized by observation of much pain and uncertainty. For all but 3 mothers, the interview was conducted within the range of 2 weeks before to 2 weeks after the child’s transplantation (2 mothers were interviewed between 7 and 8 weeks before the child’s BMT/SCT and 1 mother was interviewed 27 days after the child’s BMT/SCT). Time 2 was conducted approximately 3 months after the date of the child’s transplantation (M = 103 days; SD = 19.01 days; range = 70 to 171 days post-BMT/SCT).

Measures
Only those measures from the larger study that are relevant to the cognitive process model tested here are reported. For children undergoing BMT/SCT, a number of medical risk factors can place them at higher risk for an unsuccessful transplantation outcome including type and status of illness, the risk of the transplantation, and posttransplant medical problems. In terms of the disease risk, factors include whether the underlying disease is malignant, the type of malignancy and whether or not the malignant condition has been in remission since treatment began. Transplantation risk factors include whether the transplant was autologous or allogeneic, and the match between the donor and child. Post-BMT/SCT infusion problems include a transfer of the child to the Intensive Care Unit (ICU) and if the child develops graft vs. host disease or other organ toxicities.

Medical Risk
Two general indicators of medical risk were created by the pediatric transplantation physicians. The first variable was labeled disease risk. There were 4 categories: nonmalignant disease (eg, autoimmune disorders), early stage (eg, Acute Lymphoblastic Leukemia (ALL) in continuous remission), intermediate stage (eg, ALL in second or greater remission), and advanced stage (eg, Refractory leukemias). The second variable was labeled transplant risk and comprised 3 categories: good, intermediate, and poor risk. A good risk BMT/SCT was for disease that was in continuous remission before BMT/SCT, an autologous transplant, and a matched sibling donor. An intermediate risk BMT/SCT was a transplantation performed for non-Hodgkin’s lymphoma, Hodgkin’s disease, AML or ALL in second or greater remission, CML, solid tumor, or a donor that was either unrelated or matched parent or other family member. A poor risk BMT/SCT was a transplantation performed for refractory or relapsed disease, solid tumors such as CNS disease, or a donor who was a nonmatched unrelated donor or mismatched family member. Medical course variables were generated for the 2 time points. At the time of hospital discharge (Time 1 for those variables), the hospital medical variables were documented. These variables included whether the child was transferred to the ICU during hospitalization, the Bearman Organ Toxicity score (27), and whether or not the child developed acute graft vs. host disease (GvHD). At the Time 2 follow-up interview, medical course variables included whether or not the child developed acute GvHD and the number of hospitalizations since the child was discharged post-BMT/SCT (Table 1). The length of hospital stay was not included in the study analyses as this variable is inherently heterogeneous because the number of days spent in the hospital is based on the patient’s diagnosis, progenitor source, transplant type, and degree of match.

Fear Network
As previously described (25) the measure of Fear Network was developed for the larger study. The 3 components of the Fear Network (Threat to Life, Potential for Suffering, and Magnitude of Fear) were conceptually derived based on the description of Fear Network in the literature (eg, 9, 12, 28, 29). One item assessed the mother’s perception of Threat to Life: "How scared are you that your child’s treatment will not be successful?" on a 9-point scale (from 0 = not at all to 8 = extremely). Three items estimated the mothers’ perception of Potential for Suffering: "How scared are you that you’ll never be able to put the cancer experience behind you?" on a 9-point scale (from 0 = not at all to 8 = extremely); "Overall, how well would you say your child has adjusted to the demands of his/her treatment?" on a 5-point scale (from 1 = not at all well to 5 = extremely well, reverse coded); "How distressed is your child about his/her illness?" on a 4-point scale (from 1 = extremely distressed to 4 = not at all distressed, reverse coded). Magnitude of Fear consisted of a combined score of the intensity and frequency of the mothers’ fears created by adding these 2 variables. The interviewer recorded the fears that the mother listed in each of 6 domains of the child’s daily life: child physical health, child mental health, social interactions, school activities, family interactions, and future concerns. Mothers rated how frequently they had the 2 most-pressing worries on a 7-point Likert scale (from 1 = almost never to 7 = all the time), and the intensity of these fears on an 11-point Likert scale (from 1 = not at all intense to 100 = intense as could be). As the 3 Fear Network components employed different scales, they were transformed to standard scores before the calculation of scale reliability. In the present sample, the internal consistency coefficients for fear network at Time 1 and Time 2 were adequate (alpha = 0.73; and alpha = 0.75 respectively).

Cognitive Processing
Although the Impact of Events Scale (IES) (13) has been used as a measure of distress in prior research, recent theorists propose that it may be useful as a measure of cognitive processing (15). In this study the IES is used as a measure of cognitive processing. The IES is a 15-item self-report measure focusing on intrusions and avoidance associated with a stressor, in this case the child’s cancer and its treatment. Using a 4-point Likert scale mothers were asked to rate how true each statement had been for them during the past 4 weeks. To confirm the presence of 2 factors, a confirmatory factor analysis was conducted with the IES using Structural Equation Modeling (SEM). At both times, a 2-factor solution fit the data extremely well (Time 1: {chi}2= 1.11, p = .29; Root mean square error of approximation (RMSEA)= 0.034, p = .35; Comparative Fit Index (CFI)= 1.0; Standardized root mean square residual (SRMR)= 0.018; Time 2: {chi}2= 0.21, p=.65; RMSEA = 0.0, p = .68; CFI = 1.00; SRMR = 0.0048). At both times, all items representing IES Intrusion and IES Avoidance loaded only on their respective factors. Furthermore, a 1-factor solution at both times fit the data poorly and was a significantly worse fit than the 2-factor solution. A {chi}-square difference test between a 1- and 2-factor solution at both assessment times favored the 2-factor solution (Time 1 {chi}2 difference = 20.66, df = 1, p < .001; Time 2 {chi}2 difference = 9.28, df = 1, p < .01). A recent review addressing the psychometric properties of the IES also supported the 2-factor structure (30). Based on prior research and these data, separate Intrusion (IESI) and Avoidance (IESA) scores were computed and the internal consistencies for both scales were good to adequate (IESI baseline coefficient alpha = 0.81; 3-month follow-up coefficient alpha = 0.84; IESA baseline coefficient alpha = 0.68; 3-month follow-up coefficient alpha = 0.76).

Psychological Distress
Two self-report instruments, the Beck Anxiety Inventory (BAI) (31) and the Beck Depression Inventory (BDI), were used as indicators of distress. The BAI is a 21-item scale used to assess symptoms of anxiety and each item is rated from 0 = Not at all to 3 = Severely: I could barely stand it. Internal consistency for the present sample was good (baseline and 3-month coefficient alphas = 0.89 and = 0.93, respectively). The BDI (32) is a 21-item scale used to assess depressive symptoms, and each item is rated from not having the symptom to having it severely or intensely (eg, 0 = I do not feel sad to 3 = I am so sad or unhappy that I can’t stand it). In the present sample, internal consistency was good (baseline and 3-month coefficient alphas = 0.86 and = 0.84, respectively).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Overview of Data Analysis
Missing data were handled as follows. For individuals with 10% or less missing data on a scale, the scale mean for that individual was used for missing item(s). Participants with > 10% missing data on a scale were excluded from the relevant analyses. Missing data were minimal and this procedure was used to avoid list-wise deletion of data.

Analyses were conducted in 4 stages. First, descriptive statistics were generated. Second, the relations between model variables and potential control variables (ie, the mothers’ sociodemographic characteristics, the child’s medical indicators, and the time between the first and second assessment) were examined. Third, the fit of the proposed model to the data were assessed with Structural Equation Modeling (SEM) using the program LISREL 8 (33). One of the most commonly used measures of overall fit is the chi-square test (35). However, as this goodness of fit measure is sensitive to sample size, a number of alternative fit indices have been suggested to gauge the adequacy of the model (36, 37). The current recommendation for SEM is that multiple indicators of fit should be reported (38). Accordingly, the overall fit measures used here were the chi-square goodness of fit (35), the CFI (36), the SRMR, the RMSEA, and the Incremental Fit Index (IFI) (35). For the various fit indices, values equal to or greater than 0.90 and SRMRs of less than 0.08 are taken to indicate a good fit. The RMSEA should be nonsignificant (35). Additional direct tests of mediation were also performed. Fourth, SEM was used to test the fit of an alternative model.

The hypothesized model is illustrated in Figure 1. SEM provides a method for testing the plausibility of hypothesized relations between latent or manifest variables. In SEM models, latent variables, which model the common variance of the measured or observed variables that serve as their indicators, are represented by circles and measured variables are represented by rectangles. In SEM the hypothesized concurrent and longitudinal relations, including mediational relations, are tested simultaneously (34). The latent variables of Distress, Intrusions, and Avoidance were formed using the following indicators: the BDI and the BAI for Distress; the IESI subscale of the IES for Intrusions, and the IESA subscale of the IES for Avoidance. For SEM, latent variables should have at least 2 indicators (38). The items for the IESI and IESA were randomly split into 2 clusters to form the indicators of the Intrusion and Avoidance latent variables. Compared with using individual scale items, item clusters tend to have greater reliability, result in more normal distributions, and require fewer parameters to estimate (39). Fear network had 3 indicators: Threat to Life, Potential for Suffering, and Magnitude of Fear.

Descriptive Data
Descriptive information for each measure and the latent variable indicators employed in the SEM analyses are reported in Table 2. Although SEM results are minimally affected by low to moderate nonnormality, 3 efforts were made to normalize the variables used in the SEM analyses. First, selected individual IES items at Time 1 and Time 2 were re-coded to improve their distributions before creating the Intrusion and Avoidance clusters described above. Second, some of the scales were mildly kurtotic and were transformed to reduce the kurtosis before their use in the SEM. Winsorizing transformations were conducted on the data for 2 of the medical indicators (ie, the Bearman Organ Toxicity Scale and the number of hospitalizations) as well as Time 1 Depression and Time 2 Anxiety. Third, to ensure that the standard deviations of the variables employed in the SEM were approximately equal, variance stabilizing transformations were used. For Time 1 and Time 2 Anxiety and Depression and Fear Magnitude, the variables were re-scaled by dividing the total score by an appropriate constant so that their standard deviations were comparable. As Hatcher noted (51), the new standard deviations have no effect on the correlations among the variables.


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  		TABLE 2. Descriptive Statistics of Variables Included in the Analyses
 
Examination of Potential Covariates
First, the relations of the mothers’ sociodemographic characteristics with model variables were examined. There were no significant correlations among marital status, education, income, and child’s gender with the observed variables for the latent variables at Time 1. However, race/ethnicity (Caucasian vs. all others) correlated significantly with Time 1 intrusion clusters (Intrusion Cluster 1, r = 0.35, p < .05; Intrusion Cluster 2, r = 0.22, p < .05). Caucasian mothers reported significantly higher levels of intrusions compared with mothers of other racial/ethnic groups. Consequently, ethnic status was included in SEM analyses.

Second, relations among the child’s medical indicators and the mothers’ Fear Network variables were investigated. There were no significant associations between the pre-BMT/SCT risk categories (ie, disease risk and transplantation risk) and the components of the Fear Network at Time 1. Examination of the medical course variables indicated that Acute GvHD at the time of hospital discharge was marginally associated with Time 2 Magnitude of Fear and Potential for Suffering (r = 0.20; p = .057; r = 0.20; p = .06). There were no significant associations between transfer to the ICU or Bearman Toxicity and components of the Fear Network at Time 2. Acute GvHD at Time 2 was associated with Time 2 Potential for Suffering (r = 0.22; p < .05)(Table 4). There were no significant associations between the number of times the child was hospitalized since his/her discharge post-BMT/SCT and components of the Fear Network at Time 2. Based on these results, Acute GvHD at the time of hospital discharge and at Time 2 were examined in the SEM. Possible relations among the model variables and the number of days between the Time 1 and Time 2 interviews were investigated; no associations were found.


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  		TABLE 4. Pearson Correlation Coefficients for Cognitive Processing Model Components at Time 2
 
Estimation of the Proposed Structural Equation Model
The proposed model included 4 latent variables at each time of assessment (ie, Fear Network, Intrusion, Avoidance, and Distress), and tested both the concurrent (eg, Time 1 Fear Network with Time 1 intrusion) and longitudinal (eg, Time 1 distress with Time 2 distress) relations. A single factor representing race/ethnicity as a covariate was included. SEM was based on the correlations shown in Tables 3 to 5GoGo. Although prior analyses suggested that GvHD at the time of hospital discharge and at Time 2 were associated with Fear Network components, there were no significant associations in the SEM analysis and GvHD was removed from the model.


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  		TABLE 3. Pearson Correlation Coefficients for Cognitive Processing Model Components at Time 1
 

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  		TABLE 5. Pearson Correlation Coefficients for Cognitive Processing Model Components at Time 1 and Time 2
 
A test of the proposed model (Fig. 1) indicated the fit was adequate {chi}2= 212.87; p = .0007; RMSEA = 0.067; p = .10; SRMR = 0.08; CFI = 0.90; IFI = 0.91. Consistent with our hypotheses, for both time points the Fear Network was associated with intrusions and intrusions were associated with avoidance. Avoidance was directly associated with distress only at Time 2. In addition, Time 1 avoidance was associated with Time 2 intrusions and with Time 2 avoidance, Time 1 Fear Network was associated with Time 2 Fear Network, and Time 1 distress was associated with Time 2 distress. As a first attempt to improve the fit of the SEM, we eliminated the 3 nonsignificant paths (ie, the path from Time 1 intrusions to Time 2 distress, Time 1 intrusions to Time 2 avoidance, and Time 1 intrusions to Time 2 intrusions). After eliminating these nonsignificant paths, fit indices suggested that the fit of the model was worse than the original model. Modification indices were examined to identify which additional paths would significantly improve the fit of the model to these data guided by conceptual considerations and potential covariates. The following 5 paths were added: 1) Time 1 intrusions to Time 1 distress; 2) Time 1 Fear Network to Time 1 distress; 3) race/ethnicity to Time 1 avoidance; 4) race/ethnicity to Time 2 intrusions; and 5) the child’s transplant risk to mothers’ Time 2 distress. After these 5 paths were added, the model fit was {chi}2 (151)= 176.53, p= .076, which indicates a good fit to the data. This final model is illustrated in Figure 2. The alternative fit indices also indicated that this model provided a good fit to the data. The CFI and IFI indices were both 0.94, the SRMSR was 0.06, and the RMSEA was 0.04 and not significant (p =. 65). SEM included the mediational (ie, indirect) relations as all paths were tested simultaneously as specified in the model. However, additional direct tests of mediation were also performed using the approach described by Holmbeck (40). All mediating relations noted above were again found with this approach (details available on request from the authors).



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  		Fig. 2. A cognitive processing model of psychological distress at Time 1 and Time 2.

 
Estimating an Alternative Model
To test the fit of a proposed model, SEM procedures typically compare the fit of the proposed model with the fit of a null model. An alternative approach is to test the model as compared with a meaningful competing model. The main competing model to the one proposed is a model based on the work of Horowitz (11,13) in which avoidance precedes intrusions and intrusions are directly associated with distress. To test this alternative model, the final model was analyzed with the sequence of Fear Network to avoidance, avoidance to intrusions, and intrusions to distress at each time point. The alternative model constituted a poorer fit to the data ({chi}2= 212.42, p = .0011; RMSEA = 0.066, p = .12; CFI = 0.90; IFI = 0.91; RMSR = 0.079) than the final model. Since the alternative model is not nested within the final model, a chi-square difference test could not be conducted. Instead, the Akaike Information Criterion (AIC) was examined. With the AIC, a smaller number represents a better-fitting model (41). The AIC for the final model was 294.53 and the AIC for the alternative model was 326.42. These results indicated that the model with intrusions preceding avoidance provided the better fit.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
The results of this study were generally consistent with the application of a cognitive processing model for understanding mothers’ distress during the course of their child’s transplantation and posthospital recovery. The study results also converge with findings from prior research (9,15) suggesting that fears, intrusions, and avoidance play a critical role in the experience of distress with a stressful event. There were 4 primary study findings. First, results indicated that mothers’ fears play a critical role in mothers’ distress both during and after the child’s transplantation. Second, the data supported the proposed role for intrusions as a mediator between mothers’ fears and distress. Third, the results regarding a mediating role for avoidance were inconsistent. Fourth, the child’s transplantation risk was associated with mothers’ distress. There also was one secondary study finding: Caucasian mothers had higher levels of intrusions and lower avoidance as compared with all other mothers.

We hypothesized that pediatric BMT/SCT would lead to the development of a Fear Network that would be associated with mothers’ distress. The results from the present study support this hypothesis. At both times of assessment, mothers who had a greater Fear Network were more distressed. Our findings also suggest that mothers’ Fear Network is a more important predictor of mothers’ distress than the objective medical risk and medical course indicators reported. These results converge with prior research regarding the importance of the perception of event severity to psychological adjustment in mothers of pediatric cancer patients (42), with individuals who witnessed an office shooting (15), and with survivors of burn injury (43). Our findings highlight the importance of appraisal processes in mothers’ adjustment and are consistent with seminal theories on the importance of appraisals in how people cope with stressful life events (eg, 44, 45). Our findings regarding a mediating role for intrusions were consistent with our hypothesis. Fears were associated with intrusions, which were in turn associated directly with distress during the child’s hospitalization. Fears were indirectly associated with distress through intrusions and avoidance after the child’s hospitalization. In addition to the mediated relation, at the initial assessment there was a direct relation between Fear Network and distress. This finding requires further investigation, but suggests that at that time the mother’s appraisal of the event and the associated reactions have not coalesced, and her fears are not yet fully associated with her intrusions. This finding also suggests that there may be additional variables not included in this study that mediate the relation of fear and distress. Contrary to our study hypothesis, initial levels of intrusions were not predictive of subsequent lower levels of distress. This null finding may be due to a number of factors including that the follow-up time of assessment may not have been of sufficient duration to allow for this relation to be manifested. Creamer et al. (15) found that high intrusions 8 months after a shooting predicted lower distress 6 months later. Alternatively, perhaps when one’s child survives a BMT/SCT, relief or another variable facilitates cognitive processing, leading to less distress.

The results regarding the hypothesized mediational role of avoidance were inconsistent. During their child’s hospitalization, mothers’ intrusions were directly associated with their distress, and avoidance did not serve as a mediator. These data together with the results by Manne et al. (19) who found that avoidance mediated the relation between intrusions and distress in late-stage, but not early-stage cancer patients, suggest that the role of avoidance may vary depending on where the patient is in the process of his/her cancer treatment and recovery. Prior theorists have also suggested that the relation of adjustment and a coping process may vary depending on the phase of the event (ie, acute vs. chronic) (45). Furthermore, although the mothers’ avoidance during the child’s BMT/SCT was not associated with their concurrent levels of distress, mothers’ avoidance during their child’s BMT/SCT hospitalization was indirectly associated with their distress 3 months later. These longitudinal data are consistent with Creamer et al.s’ prior research suggesting that when avoidance is employed, processing of the event is inhibited, resulting in subsequent distress (15). This finding also supports the proposal by theorists such as Horowitz (9, 11, 13, 15) that the relations of intrusions and avoidance may be cyclical. That is, intrusions lead to attempts to avoid, and when avoidance is employed intrusions subsequently increase, and the cycle of intrusions and avoidance to distress continues. The study results also indicated that the proposed sequence of intrusions to avoidance fit these data better than a model in which the order was reversed. There may be many additional alternative models, which were not tested here. For example, the relation of intrusions and distress may differ for individuals who have different levels of avoidance (eg, an interaction effect between intrusion and avoidance and/or different associations among individuals with extreme levels of avoidance). Investigation of alternative models is an area for future research.

Medical variables were hypothesized to play a critical role in the development of the mothers’ Fear Network. However, in the final model, these variables were not associated with the mothers’ Fear Network. In the final model, transplant risk was directly associated with mothers’ distress during the child’s posthospital stage of recovery. This relation requires replication and suggests that there may be additional variables not included in the study that mediate this relation. Overall, in the final model the medical variables were less important to mothers’ fears and adjustment than hypothesized.

There was one secondary study finding. Caucasian women had more intrusions and less avoidance during their child’s transplantation as well as more intrusions after their child’s hospital discharge. Racial/ethnic differences are difficult to interpret as they may represent other factors. For example, Caucasian women were more likely to report a higher annual household income and to be older than women of other racial/ethnic groups. In the univariate analysis, income and age were not associated with the intrusion and avoidance clusters, but they were associated with the mothers’ anxiety after the child’s hospitalization. At that time, women with lower income levels and who were younger reported higher levels of anxiety. However, when income and age were analyzed simultaneously (ie, in regression analysis) neither were associated with the mothers’ post-BMT/SCT anxiety. Thus, although these data suggest that racial/ethnic group may be an indicator of another factor such as income, they are inconclusive. A more heterogeneous group of women is needed to explore issues of racial/ethnic and cultural variations.

Study Limitations and Areas for Future Research
There are 5 study limitations that point to areas in need of future research. First, although our measure of Fear Network has many strengths (eg, it was stable over time, and all Fear Network indicators loaded appropriately and significantly), it only assesses conscious worries and fears. According to Brewin et al.’s dual representation theory, conscious representation is only one type of representation associated with trauma (18, 46) . In addition, one of the constructs, "threat to life," was represented by a single item. This single-item indicator as well as our multiple component Fear Network measure requires further validation in other trauma populations. Future research examining individual differences in the formation of fear representation is also needed. For example, based on the work of Carver et al. (47) mothers who are optimists may appraise their child’s transplantation as less threatening, and develop smaller Fear Networks. In contrast, based on the work of Foa et al. (28), individuals with a history of trauma may be primed to develop larger Fear Networks. The amount of trauma exposure (eg, number of hours a mother spent on the transplant unit) may also be associated with mothers’ fear, although this may not vary among mothers. Research investigating what factors are associated with fears would help to identify mothers at less or more risk for distress. Furthermore, despite evidence suggesting that fears, intrusions, avoidance, and distress are different constructs, further validation regarding their areas of independence and overlap is needed.

Second, this study focused on cognitive processing as measured by the IES. Support for the application of the IES as a measure of processing and of the IES as comprising separate components of intrusions and avoidance comes from prior research as well as the present study. However, the IES does not assess other cognitive processes such as the search for meaning in the event. The development of a more comprehensive measure of cognitive processing is an area for future research. Furthermore, Brewin et al. (18) have pointed out the necessity of including other types of processing. For example, as suggested by prior researchers (21–24, 49) people may process events through talking with others. Research with alternative types of processing such as social processing warrants investigation. Third, the course of the study was limited to 2 times of assessment—during the child’s BMT/SCT hospitalization and 3 months later. In addition, it is not clear that the assessment during the child’s BMT/SCT represented a true baseline assessment of the mothers’ fears, intrusions, avoidance, and distress. The issue of a true baseline1 is complex and it is not immediately apparent what would be the most relevant time for baseline assessment: it could be before the child’s BMT/SCT, at the time of the child’s diagnosis, or before the initiation of the child’s treatment. Fourth, there was variability in the mode of data collection (over the telephone or in person). It would be important in future research to investigate possible differences based on mode of assessment in this and other populations. Fifth, the use of modification procedures to refit portions of the model under consideration is data driven, and capitalizes on chance (50). Replication of the study results in another sample is warranted. Despite these limitations, these data provide the first steps in the examination of cognitive processes among mothers of BMT/SCT patients.

Clinical Implications
The study results suggest that interventions that focus on reducing the mothers’ fears about their child’s BMT/SCT may be effective in reducing distress. For example, preparatory information pre-BMT/SCT about what to expect during the transplantation course and recovery, and discussions about the meaning of the event may facilitate assimilation of the child’s BMT/SCT into the mothers’ world view and minimize mothers’ fears. Additional intervention strategies such as identification of cognitive distortions and systematic desensitization may facilitate the accommodation of the BMT/SCT into mothers’ existing cognitive schemas and thereby reduce the incongruence between the mothers’ schemas and the event. Skills training including relaxation exercises, self-monitoring or journaling, and positive cognitive coping self-statements may also reduce mothers’ distress by helping them cope with their fears. These data also suggest that psychological intervention should emphasize the detrimental effects of following the urge to avoid fears and intrusions. These results suggest that it may be beneficial for hospital staff to inform mothers that their efforts to be engaged in their child’s care and not avoid their fears may not only benefit their child, but may also help them adjust during the child’s posthospital recovery. These clinical implications are consistent with the current focus on the modification of threat memories and the reduction of avoidance in cognitive-behavioral interventions for survivors of traumas (28, 48).


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
REFERENCES
 
This work was supported by Grant MH 57738 awarded by the National Cancer Institute and the National Institutes of Mental Health. Katherine DuHamel’s work was also supported by the American Cancer Society Award number RPG-99-271-01-PBP as well as supported by the US Army Medical Research and Material Command under Award Number DAMD17-99-1–9304. The views, opinions, and/or findings contained in this document are those of the authors and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation.

We thank the mothers of the pediatric bone marrow/stem cell transplant patients who participated in this study. We also acknowledge the contributions of Jane Austin, PhD, Christine Rini, PhD, Julie Lewis, PhD, Maria Kangas, PhD, Suzanne M.J. Vickberg, PhD, Dana Spencer, Dorothy Parks, Jean Grieff, Alyssa Lowther, Erin Olivo, Jennifer Soriano, Chris Martinez, Nina Babat, Anne McDevitt, Angelica Ware, Bonnie Maxson, and Julian Silva for their assistance in manuscript preparation, data collection, or data management. We also appreciate the assistance of the oncologists on the pediatric transplant services, including Michael Amylon and Morris Kletzel. We would also like to thank our anonymous reviewers for their feedback.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
ACKNOWLEDGMENTS
 REFERENCES
 
1The comments regarding what would be a "true baseline" is the summary of a discussion conducted within the context of the 2001 Expert Lectures in Biobehavioral Aspects of Cancer, Prelude to the 22nd Annual Meeting of the Society of Behavioral Medicine, Seattle, Washington. Back

Received for publication September 5, 2002.

Revision received June 14, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 

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