Eating Behaviors 12 (2011) 44–48
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Eating Behaviors
The impact of perceived social support and negative life events on bulimic symptoms Lindsay P. Bodell a,⁎, April R. Smith a, Jill M. Holm-Denoma b, Kathryn H. Gordon c, Thomas E. Joiner a a b c
Florida State University, Department of Psychology, United States University of Denver, Department of Psychology, United States North Dakota State University, Department of Psychology, United States
a r t i c l e
i n f o
Article history: Received 15 April 2010 Received in revised form 5 October 2010 Accepted 4 November 2010 Keywords: Social support Negative events Bulimic symptoms Disordered eating
a b s t r a c t Objective: The purpose of the current study was to evaluate the relationship between social support, negative life events, and disordered eating using a longitudinal design. More specifically, we examined whether the interaction between perceived social support and occurrence of negative life events would predict symptoms of eating disorders. Method: Two hundred seventy female undergraduate students completed self-report questionnaires at two time points to assess perceived social support, negative life events experienced, and current psychopathology. Results: Low social support and a greater number of negative life events interacted to predict increased bulimic symptoms, but not restrictive eating tendencies or symptoms of depression or anxiety. Discussion: Low perceived social support in the face of negative events may exacerbate bulimic symptoms. Management of interpersonal problems and the enhancement of social skills may be important targets in the treatment of eating disorders. © 2010 Elsevier Ltd. All rights reserved.
1. Introduction Bulimia nervosa (BN) affects approximately one to three percent of women and symptoms tend to persist over time (American Psychiatric Association, 2000; Joiner, Heatherton, & Keel, 1997). Several risk factors for both the onset and maintenance of the disorder have been identified including body dissatisfaction, negative affect, and maladaptive coping skills (Stice, 2002). Although several studies have indicated that women with eating disorders frequently report interpersonal problems and dissatisfaction with social support (Grissett & Norvell, 1992; Rorty, Yager, Buckwalter, & Rossotto, 1999; Tiller et al., 1997), interpersonal risk factors for eating disorders have been given less attention. According to the escape theory of binge eating (Heatherton & Baumeister, 1991), individuals binge eat to “escape” from or reduce negative self-awareness. In turn, individuals may be particularly susceptible to binge eating when they lack other coping skills or means of support (e.g. seeking support from a friend), especially when faced with stressful life events. The current study aimed to investigate whether low social support in the face of negative life events would predict the occurrence of bulimic symptoms. Researchers have consistently found an association between poor social functioning and disordered eating behaviors. For example, women with BN have been found to have less social competence (Grissett & Norvell, 1992), smaller social networks (Tiller et al., 1997; ⁎ Corresponding author. Florida State University Department of Psychology, 1107 West Call Street, Tallahassee, FL 32306, United States. Tel.: +1 602 570 8692. E-mail address:
[email protected] (L.P. Bodell). 1471-0153/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.eatbeh.2010.11.002
Rorty et al., 1999), less social support (Tiller et al., 1997), and higher levels of interpersonal distress (Hartmann, Zeeck, & Barrett, 2009) than the comparison samples. In a study examining the relationship between BN recovery status and social support, Rorty et al. (1999) found that individuals with current or past BN reported significantly greater dissatisfaction with emotional support from relatives compared to the control group, suggesting that some interpersonal problems may persist after recovery from BN or that social support dissatisfaction may be present in those susceptible to BN regardless of whether they are currently ill. Steiger, Gauvin, Jabalpurwala, Seguin, and Stotland (1999) found that individuals with current BN rated negative social interactions as significantly worse in the time period prior to binge episodes than on days when binge eating was absent, further highlighting that social factors may influence the occurrence of future binge episodes. Overall, interpretations of these studies' results are limited given the cross-sectional designs. Longitudinal studies also have found a relationship between interpersonal functioning and eating disorder symptoms over time. Low perceived social support has been associated with worse eating attitudes in a female college sample (Jackson, Weiss, Lunquist, & Soderlind, 2005) as well as onset of binge eating in adolescent girls (Stice, Presnell, & Spangler, 2002). However, interpretations of the latter study are limited, because they did not control for a lifetime history of binge eating. In another study, Keel, Mitchell, Miller, Davis, and Crow (2000) found that poor social adjustment persisted even after recovery from BN, suggesting that interpersonal impairment may represent an underlying vulnerability from which disordered eating developed. Similarly, interpersonal problems prior to treatment have been associated with greater binge severity at the end of
L.P. Bodell et al. / Eating Behaviors 12 (2011) 44–48
treatment, further suggesting that interpersonal problems may play a role in the maintenance of bulimic symptoms and treatment response (Hartmann et al., 2009). In support of these interpretations, poor social adjustment (Agras et al., 2000) and dissatisfaction with social support (Bell, 2002) have been associated with poorer response to treatment in patients with BN. Interpersonal support may be particularly crucial to an individual's mental health when negative life events occur. To our knowledge, no studies have examined how social support and negative life events may interact to predict bulimic symptoms, though some studies have examined the impact of negative life events on the development of BN symptoms. In a retrospective study examining life events in the six months preceding the onset of BN, Raffi, Rondini, Grandi, and Fava (2000) found that compared to control participants, individuals with BN reported significantly more stressful life events and rated more events as having a moderate or severe impact on them. In a community-based case-controlled retrospective study, Welch, Doll, and Fairburn (1997) found that frequent house moves and separation from parents occurred at a higher frequency among women with BN compared to healthy control participants; however, neither factor differentiated women with BN from general psychiatric controls, suggesting that these factors may represent general risk for psychopathology rather than specific risk factors for BN. The aim of the current study was to evaluate the relationship between social support, negative life events, and disordered eating using a longitudinal design. Specifically, we examined our prediction that low social support and many negative life events would predict greater bulimic symptoms; we further assessed whether the same interaction would also predict symptoms of restricted eating, anxiety or depression.
2. Methods 2.1. Participants Two hundred ninety two female undergraduate students who were enrolled in an introductory psychology course at a large, southeastern state university participated in this study. The study took place during three semesters (two fall and one spring semester). Two hundred students initially participated during the fall semesters and 92 participated during the spring semester. The majority of participants were in their first year of college (88%), 8% were in their second year, and 4% were in their third year or beyond. The mean age of participants at the time of data collection was 18.7 (SD = 1.42), with a range of 17 to 29 years. We excluded married participants and participants over the age of 29 (n = 2), as stressors are likely to differ between older, married women and younger, single women, and ultimately we were interested in examining the variables of interest among more traditional college students. The ethnic composition of the sample was 27% White (n = 79), 43% Black (n = 126), 25% Latina (n = 72), 1% (n = 3) Asian, and 4% biracial (n = 12). During the first semester of the study, the experimenters opened the study to women of all ethnic groups, but during the second and third semesters of data collection, only Black women and Latinas were eligible to participate. This was done in an effort to over sample women from ethnic minority groups, to address a gap in this research area. Participants completed the study at two time points that were, on average, 8 weeks apart. Participants received course credit for their participation. Of the participants who began the study, 22 (7.5%) did not return for Time 2 (T2) data collection. There were no significant differences between completers and noncompleters in terms of age, ethnicity, perfectionism, body dissatisfaction, self-esteem, depressive symptoms, anxiety symptoms, or binge eating severity (p N .05, for all variables). All subsequent statistics and analyses refer to the 270 participants who completed both Time 1 (T1) and T2 assessments.
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2.2. Procedure All participants signed a consent form agreeing to participate in the study. Participants were informed that they would be filling out questionnaires about their personal views, feelings, and attitudes. At the end of the T2 appointment, participants were debriefed and all questions and concerns were addressed by the experimenters. All procedures were approved by the university's Institutional Review Board. 2.3. Measures 2.3.1. Negative Life Events Questionnaire (NLEQ) (Metalsky & Joiner, 1992) The NLEQ was used to quantify the number of negative life events that occurred during the time interval between the T1 and T2 assessments. Respondents were asked to indicate which life events they experienced from a list of 66 potential life stressors (e.g., did poorly on or failed an exam or major project in an important course — i.e., a grade of C or worse, fired or laid off from a job, found out family member has a life-threatening illness, romantic partner ends relationship). This measure was specifically designed for a college student population and the list of life events spans multiple domains (school, job, achievement, parents and family, roommates, friends, and romantic partners). Scores are computed by totaling the number of negative life events experienced and can range from 0 to 66. The scale has demonstrated validity and adequate reliability in previous studies (Metalsky & Joiner, 1992) and excellent reliability in the current sample (α = .96). 2.3.2. Social Support Questionnaire (SSQ-6) (Sarason, Sarason, Shearin, & Pierce, 1987) Perceived social support was measured at T1 with the SSQ-6, a self-report instrument that asks six questions about respondents' perceived number of social supports and their satisfaction with their level of social support. For example, the first question asks, “Who can you really count on to be dependable when you need help?” Respondents are asked to respond by listing people in their life who fit the description in the question by name or initials, and then rate how satisfied they are with their overall support on a scale ranging from 0 (very dissatisfied) to 6 (very satisfied). The SSQ-6 yields two scores: a Number of Availability score based upon the number of people listed per question and a Satisfaction score based on ratings on the second part of the question. The SSQ-6 has demonstrated good reliability and validity in general (Sarason, Shearin, Pierce, & Sarason, 1987) and in undergraduate samples specifically (Brock, Sarason, Sarason, & Pierce, 1996). In the current study, we focused on the Satisfaction score, as many past studies have identified this dimension as the more crucial (Sarason, Shearin, et al., 1987); the Satisfaction subscale had good reliability in the current sample (coefficient alpha = .96). 2.3.3. Eating Disorder Inventory subscales (EDI) (Garner, Olmsted, & Polivy, 1983) The EDI is a self-report inventory that consists of 64 questions about attitudes and behaviors related to eating disorders. It yields eight subscale scores, two of which were the focus of the current study. The EDI-Bulimia (EDI-B) and EDI-Drive for Thinness (EDI-DFT) subscales were included because they are most explicitly linked to eating disorder symptoms. The EDI instructs participants to rate statements on a six-point scale (1 = never to 6 = always). The EDI-B subscale includes items such as, “I stuff myself with food,” and the coefficient alpha in this sample was .85 at T1 and .88 at T2. The EDI-DFT scale includes items such as “I think about dieting,” and the coefficient alpha in this sample was .92 at T1 and .90 at T2.
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2.3.4. Beck Depression Inventory (BDI) (Beck, Steer, & Garbin, 1998) Depression symptoms were assessed with the BDI, which is a selfreport questionnaire that consists of 21 items. The respondent is asked to select one statement from a group of statements that reflects his/her current level of depression symptom severity (scored from 0 to 3). For example, one item uses the statement “I do not feel sad,” as the least severe (and would be rated as a 0), while the statement that is most severe (and would be rated as 3) is, “I am so sad or unhappy that I can't stand it.” The BDI has been shown to be reliable and valid (see Beck et al., 1998 for a review). In the current sample, the alpha coefficient was .87 at T1 and .90 at T2. 2.3.5. Beck Anxiety Inventory (BAI) (Beck, Epstein, Brown, & Steer, 1988) Anxiety symptoms were measured with the BAI, which consists of 21 cognitive and physiological symptoms related to anxiety. Participants were instructed to indicate the degree to which they were affected by certain anxiety symptoms (e.g., nervous, shaky, faint) “during the past two weeks” from 0 to 3 (0 = not at all, 1 = mildly, 2 = moderately, and 3 = severely). The alpha coefficient for the BAI in this sample was .88 at T1 and .92 at T2.
The critical test of the main hypothesis is the two-way interaction. Controlling for T1 bulimic symptoms, as well as T1 depressive and anxiety symptoms (as measured by the BDI and BAI, respectively), negative life events (measured at T2) and social support (measured at T1) interacted to predict T2 bulimic symptoms, β = −.10, t = − 2.12, p = .04, f2 (set) = 1.92, f2(interaction) = 0.02. See Fig. 1. The main effects of T1 bulimic symptoms and T1 social support also remained significant (see Table 2). To determine the nature of the interaction, we probed the two-way interaction by using “high” and “low” combinations of negative life events (using values that were one standard deviation above or below the mean). In the high negative life events group, the effect of social support on participants' bulimic symptoms at T2 was significant, β = −.23, t = − 3.11, p b .01. There was no significant effect of social support in the low negative life events group, β = −.04, t = −.81, p = .42. Thus, participants who experienced greater negative life events and low social support had increased bulimic symptoms at a later time. In the companion analysis, the interaction term did not predict T2 restrictive tendencies (i.e., EDI-DFT scores), β = .001, t = .02, p = .98. 3.3. Social support × negative life events predicting symptoms of depression and anxiety
3. Results 3.1. Sample characteristics There were small but significant decreases in bulimic symptoms from T1 to T2 (T1 mean = 12.88; and T2 mean = 12.15, t = 3.50, p b .001) and in anxiety symptoms from T1 to T2 (T1 mean = 27.39; and T2 mean = 25.79, t = 5.19, p b .001). These decreases are likely the result of regression toward the mean. Additionally, there were some significant differences in the mean scores on variables of interest by ethnicity (see Table 1). 3.2. Social support × negative life events predicting Time 2 bulimic symptoms Two regression analyses were conducted to examine the potential two-way interaction between negative life events (as measured by the NLEQ) and social support (as measured by the Satisfaction score of the SSQ-6) on eating disorder symptoms. In prediction of T2 bulimic symptoms (as measured by the EDI-B subscale), the following predictors were entered: Step 1 — T1 bulimic symptoms; Step 2 — simultaneous entry of the two centered main effects (negative life events and social support) to assess the simple effects of the predictor variables; and Step 3 — entry of the two-way interaction (negative life events × social support). In the prediction of restrictive symptoms (as measured by the EDI-DFT subscale), the entry of Steps 2 and 3 remained the same; however, T1 restrictive eating symptoms were entered in Step 1.
Two additional regression analyses were conducted in order to determine whether the interaction between negative life events and social support was uniquely related to the prediction of bulimic symptoms, or whether it also predicted other internalizing symptoms. Therefore, we examined whether the interaction predicted T2 depressive and anxiety symptoms (as measured by the BDI and BAI, respectively). In the regression analysis predicting T2 depressive symptoms, T1 depressive symptoms were entered in the first step, followed by the centered main effects in the second step, and the interaction term in the third. In the regression analysis predicting anxiety symptoms, T1 anxiety symptoms were entered in the first step, followed by the centered main effects in the second step, and the interaction term in the third step. The interaction between negative life events and social support did not predict depressive symptoms (β = −.06, t = −1.03, p = .31); however there were significant main effects of T1 depression and negative events on T2 depression (see Table 3). The interaction between negative life events and social support also did not predict anxiety symptoms (β = .02, t = .41, p = .68; see Table 4). Thus, the interaction of social support and negative life events appears to predict uniquely bulimic symptoms. 4. Discussion The present study investigated the role of social support and negative life events on eating behaviors. Additionally, the study examined the specificity of the relationship between social support
Table 1 Comparison of ethnic groups on predictor and dependent variables. Black N = 121
M
M
SD a
15.8 14.5a 24.0a 22.1a 28.8 27.4 28.9a 26.5 103.4 30.6
6.5 5.0 9.4 8.8 7.3 6.4 6.1 5.4 21.7 6.7
Hispanic N = 72 SD
b
10.7 10.2b 16.1b 15.2b 26.2 26.0 25.9b 24.9 100.2 31.6
3.7 2.8 7.7 7.3 6.0 5.0 5.5 4.8 30.4 7.3
M
P
SD c
13.1 12.5c 21.6a 20.2a 27.9 27.4 28.0a 26.2 98.8 29.7
5.8 5.6 9.1 8.5 7.5 6.1 6.3 5.6 19.6 8.9
b.001 b.001 b.001 b.001 .07 .20 .002 .08 .58 .38
Note: Superscripts that differ represent significant between group differences at p b .05 after Tukey HSD correction for post-hoc comparisons.
EDI Bulimia
EDI-B T1 EDI-B T2 EDI-DFT T1 EDI-DFT T2 BDI T1 BDI T2 BAI T1 BAI T2 Negative events Perceived social support
Caucasian N = 76
15 14.5 14 13.5 13 12.5 12 11.5 11 10.5 10
Low Social support High Social support
Low Negative Event
High Negative Event
Fig. 1. Two-way interaction between social support and negative life events predicting Time 2 EDI-Bulimia score.
L.P. Bodell et al. / Eating Behaviors 12 (2011) 44–48 Table 2 Interaction between negative life events and social support in the prediction of Time 2 bulimic symptoms. Step Variable
Statistics at entry β
1
2
3
(Constant) Time 1 Beck Depression Inventory Time 1 Beck Anxiety Inventory Time 1 EDI-Bulimia (Constant) Time 1 Beck Depression Inventory Time 1 Beck Anxiety Inventory Time 1 EDI-Bulimia Time 1–2 Negative Events (centered) Time 1 social support (centered) (Constant) Time 1 Beck Depression Inventory Time 1 Beck Anxiety Inventory Time 1 EDI-Bulimia Time 1–2 negative events (centered) Time 1 social support (centered) Negative events × social support (interaction)
SE
t
Step
Dependent variable: Time 2 EDI-Bulimia.
and negative life events in the prediction of increased bulimic symptoms. We found that the combination of low social support and multiple negative life events predicted bulimic symptoms but not restrictive eating or anxiety or mood symptoms. Specifically, after controlling for baseline bulimic, depressive, and anxiety symptoms, participants who experienced a greater number of negative life events and who had lower perceived social support reported increased bulimic symptoms two months later. Furthermore, despite a small overall reduction in bulimic symptoms from T1 to T2, our interaction term still significantly predicted increases in bulimic symptoms, providing some additional evidence for the strength of the interaction. To our knowledge, this is the first study to examine the concurrent association between interpersonal problems and life stressors in predicting disordered eating behavior using a longitudinal design. The current finding that perceived low social support at T1 and negative life events between T1 and T2 interact to predict increased selfreported bulimic symptoms at T2 indicates that individuals with perceived low social support may be at risk for greater disordered eating behaviors, especially when faced with stressors such as negative life events. This interpretation is compatible with the escape theory of binge eating which posits that binge eating is used as a method for escaping distress (e.g., that which stems from experiencing negative life events) (Heatherton & Baumeister, 1991). In other words, binging and purging behaviors may help reduce painful Table 3 Interaction between negative life events and social support in the prediction of Time 2 depressive symptoms. Step Variable
Statistics at entry β
1 2
3
(Constant) Time 1 Beck Depression Inventory (Constant) Time 1 Beck Depression Inventory Time 1–2 negative events (centered) Time 1 social support (centered) (Constant) Time 1 Beck Depression Inventory Time 1–2 negative events (centered) Time 1 Social Support (centered) Negative events × social support (interaction)
SE
− .631 − .572 .148 .020 − .573 .147 .002 −.061
Dependent variable: Time 2 Beck Depression Inventory.
t
1.369 9.368 .048 10.718 1.493 9.468 .052 8.852 .015 2.315 .271 .333 1.493 9.444 .052 8.870 .015 2.291 .283 .033 .012 − 1.006
Table 4 Interaction between negative life events and social support in the prediction of Time 2 anxiety symptoms. Variable
p
– .973 2.129 .035 .009 .042 0.153 .878 .067 .042 1.112 .268 .758 .046 14.965 .000 − 1.066 2.145 .033 −.003 .043 − 0.043 .965 .074 .041 1.232 .220 .747 .046 14.853 .000 .000 .010 0.004 .996 −.111 .170 − 2.498 .013 − 1.058 2.032 .044 −.005 .043 − 0.073 .942 .085 .041 1.435 .153 .742 .045 14.874 .000 −.005 .010 − 0.104 .917 −.147 .181 − 3.118 .002 −.099 .008 − 2.119 .035
p .000 .000 .000 .000 .002 .739 .000 .000 .023 .974 .316
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1 2
3
(Constant) Time 1 Beck Anxiety Inventory (Constant) Time 1 Beck Anxiety Inventory Time 1–2 negative events (centered) Time 1 social support (centered) (Constant) Time 1 Beck Anxiety Inventory Time 1–2 Negative Events (centered) Time 1 social support (centered) Negative events × social support (interaction)
Statistics at entry β
SE
t
p
– .605 – .582 .091 .059 – .579 .092 .071 .034
1.328 .047 1.384 .049 .012 .225 1.390 .049 .012 .240 .010
8.934 10.903 8.965 10.036 1.574 1.060 8.969 9.952 1.584 1.193 .581
.000 .000 .000 .000 .117 .291 .000 .000 .115 .234 .562
Dependent variable: Time 2 Beck Anxiety Inventory.
feelings or negative emotions and thus act as negative reinforcement, which may be exacerbated in times of stress coupled with low perceived social support. Furthermore, the results in the current study indicate that the relationship between social support and negative life events is specific in predicting bulimic symptoms. This interaction did not predict restrictive eating or symptoms of anxiety or depression. The finding that the interaction did not predict restrictive eating is consistent with that of Tiller et al. (1997), which found that while patients with both anorexia nervosa (AN) and BN had smaller social networks than controls, only patients with BN reported dissatisfaction with their social support. Although both eating disorder groups may experience interpersonal problems, individuals with BN may have greater disturbances in the perceived adequacy of their relationships and thus may be more likely to cope with their interpersonal problems and additional stressors by engaging in bulimic behaviors. Furthermore, bulimic symptoms in particular may be more related to coping with interpersonal problems whereas restrictive eating patterns may be more specifically related to the desire to lose weight than to cope with negative affect or stressors. Although some studies have found low social support and life stressors to be associated with depression and that high social support may be a protective factor (Aneshensel & Frerichs, 1982; Paykel, 1994; Dalgard, Bjork, & Tambs, 1995), other studies have failed to find an interaction between stress and social support in the prediction of depressive symptomatology (Aneshensel & Stone, 1982). Thus, it is somewhat surprising that in the current sample, the interaction of negative life events and low social support did not predict depressive symptoms. It is possible that the current study did not have enough power to predict depressive symptoms and may suggest that the interaction is more robust in the prediction of bulimic symptoms. Furthermore, a lack of significant change in depression from T1 to T2 may have not allowed enough range in symptoms to fully test the prediction. Alternatively, the window of time may not have been great enough to capture increases in depressive symptoms. It is possible that it takes longer for the combination of negative life events and low social support to influence mood or anxiety symptoms, whereas bulimic symptoms may occur more rapidly due to the immediate escape function they may serve. Given that perceived social support may exacerbate bulimic symptoms, managing interpersonal problems and enhancing social skills may be important targets in the treatment of eating disorders. Additionally, these findings indicate that interpersonal psychotherapy (IPT), which focuses on restoring and maintaining important interpersonal relationships may be an appropriate treatment option for individuals with BN; notably, IPT has shown some efficacy in the treatment of BN (Fairburn et al., 1995). Moreover, an important
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component of prevention efforts may be teaching people to cope with negative life events in positive ways. Some limitations of the study should be noted. Social support and negative life events were measured via self-report, and thus are susceptible to the problems inherent in using self-report data, such as incorrect or biased recall. We also used a college population, so it is unclear whether these results would hold in adolescents and other adults. Similarly, our dependent variable of EDI scores (e.g. bulimic symptoms) may not equate to clinical threshold diagnoses. Other limitations include the short interval between T1 and T2 assessments and the measurement of negative events between T1 and T2 rather than at T1 specifically. Thus, we were not able to fully control for the possibility that bulimic symptoms at T1 may have led to increased negative life events between T1 and T2 (i.e. the direction of causation of negative events and low social support predicting bulimic symptoms could be the other way). Despite these limitations, the study possesses several notable strengths, including the use of a longitudinal design, stringent covariates, and an ethnically diverse sample. Additional research should be conducted to elucidate the relationship between interpersonal problems, environmental stressors, and eating disorder symptoms. For example, future research could investigate whether certain types of negative life events have a greater impact on disordered eating than others. Future research could also examine whether the relationship between interpersonal problems, environmental stressors, and eating disorder symptoms differs by ethnic group. Overall, our findings highlight the importance of both interpersonal problems and environmental stressors in the exacerbation of bulimic symptoms. Role of funding source This study was funded, in part, by the National Institute of Mental Health grant F31MH083382 to A. R. Smith (under the sponsorship of T. E. Joiner). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. Contributors Kathryn Gordon and Jill Holm-Denoma designed the study and wrote the protocol. Kathryn Gordon and Lindsay Bodell conducted literature searches and provided summaries of previous research studies. April Smith conducted the statistical analysis and drafted the results section. Jill Holm-Denoma drafted the methods section, and Lindsay Bodell drafted the introduction and discussion sections. Thomas Joiner provided consultation for the various statistical analyses conducted; additionally, he provided feedback on several drafts of the manuscript. All authors contributed to and have approved the final manuscript. Conflict of interest All authors declare that they have no conflicts of interest.
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