Associations between adverse childhood family environments and blood pressure differ between men and women

Background It is unclear how adverse childhood family environments differentially impact adult health outcomes among men and women. This brief communication reports on the independent and joint effects of adverse childhood family environments and sex on indicators of health in adulthood. Methods & Results 213 18-55-year olds reported on their childhood family environment (Risky Families Questionnaire (RFQ); Family Environment Scale (FEStotal)) and their current perceived stress and depressive and anxious affect. Resting systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) were taken during a laboratory visit, and total cortisol output was measured in saliva samples collected at home. Exposure to childhood adversity did not vary by sex. Women had lower SBP, DBP, and total cortisol output, but higher HR, than men (ps < .05). Sex moderated the association between childhood family environment and SBP (RFQ: B = -.316; SE = .120; p = .009; FEStotal: B = -.274; SE = .117; p = .021) and DBP (FEStotal: B = -.193; SE = .094; p = .041), such that exposure to greater childhood adversity was linked to lower BP in women only. Results were largely unchanged after adjusting for concurrent perceived stress and depressive and anxious affect. Separate effects of individual FES subscales are also discussed. Conclusions Contrary to expectations, exposure to adverse childhood family environments was associated with lower resting BP among women, perhaps indicative of basal cardiovascular hypoactivation, whereas early adversity was not linked to BP among men.

Introduction on average. We further investigate the possible moderation of this association by sex. Relative to men, we expect that women may be more strongly impacted, experiencing higher BP, HR, and cortisol levels following exposure to childhood adversity compared to men. Finally, to assess whether possible effects of harsher family environments on adult physiological outcomes may be a function of affective states and/or stress exposure in adulthood, we include measures of participants' concurrent anxious and depressive affect, as well as perceived stress.

Materials and methods
Participants 213 adults (30.1 ± 10.8 years old; 123 men; 66.7% White) involved in the Pittsburgh Common Cold Project 3 (PCS3) were recruited from the greater Pittsburgh area from 2007-2011 via newspaper advertisements. Inclusion criteria were being fluent in English and being in good health as per a physician examination. Participants were excluded if they were currently pregnant, lactating, immunocompromised, diagnosed with and treated for a chronic disease or psychiatric diagnosis within the past year, or taking any regularly prescribed medications other than hormonal birth control. Men and women did not differ in age, education, race/ethnicity, marital status or employment status but women had higher body mass indices (BMI; t (130.86) = -2.246; p = .026) and were less likely to be smokers (X 2 (1, N = 213) = 6.100; p = .014); Table 1.

Procedure
Data were accessed via the Common Cold Project website (www.commoncoldproject.com; grant number NCCIH AT006694). The larger project included the experimental examination of participants' susceptibility to viral challenge; the analyses reported here use only baseline data collected prior to experimental procedures. Participants provided written consent, completed demographic and psychosocial questionnaires and reported on their daily mood over a two-week period. Participants' BP, HR, height and weight were taken during a laboratory visit and participants collected saliva samples at home. The study was approved by the institutional review boards at Carnegie Mellon University and The University of Pittsburgh.

Measures
Childhood adversity. Participants completed the 13-item Risky Families Questionnaire (RFQ) [20] assessing how frequently they were exposed to a variety of adverse physical and psychological circumstances in their childhood homes when they were 5-15 years. On a 5-point Likert scale (1 = not at all; 5 = very often), participants noted how often they experienced certain distressing events (e.g., domestic disputes; parental substance abuse) and the extent to which care and affection were provided. Positively-framed items (e.g., being hugged) were reverse scored, with higher total RFQ scores indicative of more adversity. Scores ranged from 13-63 and internal consistency was strong (Cronbach's α = .90). RFQ scores were comparable to those reported in previous reports [21,22].
Participants also completed the Family Environment Scale (FES) [23], a well-validated 25-item scale about family relationships and family system maintenance when they were 5-15 years. The three subscales making up the family relationships index (conflict; cohesion; expressiveness; 15 items) were deemed relevant to the question at hand and included here. On a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree), participants reported the extent to which they agreed with each statement. To align with the RFQ, positively-framed items were reverse scored so higher scores reflect more conflict and less cohesive and expressive family environments. Internal consistency was acceptable to very good for the overall family relationships index (FES total ; Cronbach's α = .89) and across the conflict, cohesion and expressiveness dimensions (Cronbach's α = .59-.89), which is similar to previously reported values [23].
Physiological measures. During day 0 (baseline) of quarantine, resting systolic (SBP) and diastolic (DBP) blood pressure and HR were assessed by study staff three times over the course of one day, i.e., at 8:00 AM, 1:00 PM, and 7:00 PM, using an automated, portable oscillometric blood pressure monitor (Spot Vital Signs, Welsch Allyn, Inc., Skaneateles Falls, NY, USA) and averaged across the three sessions. Height and weight were measured at two laboratory visits using a standard balance scale, BMI (kg/(m 2 )) calculated, and averaged across the two visits. Participants collected saliva samples using Salivettes (Sarstedt, Rommelsdorf, Germany) over 2 days, 7 samples per day across the day (60, 120, 240, 420, 540, 660, and 780 minutes following wakeup). Participants were advised not to eat or brush their teeth one hour before saliva collection, to abstain from smoking 30 minutes prior to collection, and were given a kitchen timer and either a preprogrammed wristwatch or handheld computer to increase compliance. Note � p < 0.05 when comparing men and women using independent sample T-tests and chi-squared tests; BMI = body mass index; RFQ = Risky Families Questionnaire; FES = Family Environment Scale; SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate. The FES was reverse scored to be in line with the RFQ.
Higher scores on the FES family relationship index and subscales are indicative of more conflict and less cohesion and expressiveness within the childhood home. One female participant who was taking corticosteroid medication was excluded from analyses for total cortisol. Cortisol levels were determined by time-resolved fluorescence immunoassays with cortisolbiotin conjugates as tracers [24]. Intra-and inter-assay coefficients of variation were < 12%. Total cortisol was estimated by calculating area under the curve (AUC) using the trapezoidal rule [25] for each day and averaging across the two days for each person. Only data from saliva samples taken within 45-90 min. following wakeup (sample 1) or within 60 min. of the prescribed time (all other samples) were included. Adult distress measures. Participants completed the 10-item Perceived Stress Scale (PSS) [26] at a pre-quarantine in-person visit. On a 5-point Likert scale (0 = never; 4 = very often), they indicated how frequently they had experienced certain thoughts and feelings over the past month (Cronbach's α = .812). Items were summed; higher scores reflect greater perceived stress. During daily, evening phone interviews over 2 weeks, participants reported how often they experienced each of 16 emotions that day on a 5-point Likert Scale (0 = they did not feel that way at all; 4 = frequently feeling that way that day). Mean depressive affect (mean of responses to 'sadness' and 'unhappiness') and mean anxious affect (mean of responses to being 'on edge' and 'tense') were calculated.

Statistical analyses
One participant reported corticosteroid medication use and was excluded from analyses for total cortisol output. Total cortisol output was not normally distributed and log transformed. All models adjusted for race/ethnicity (White vs. Non-White), age, years of education and birth control use. Models regressing BP and HR on early adversity exposure additionally adjusted for BMI. Multiple linear regression models were fit to assess the main effects of the childhood family environment and interaction effects of childhood family environment X sex on physiological outcomes. All covariates and independent variables were first centered at zero and interaction terms were created by multiplying each centered childhood family environment variable (RFQ, FES total , FES cohesion , FES expressiveness , FES conflict ) by sex (coded as 1 = female; 0 = male). Covariates and independent variables were entered in Step 1 and the interaction term was added in Step 2. When considering adult distress measures related to adult distress/dysphoria, we first examined the independent effect of each, then the effects of all 3 in saturated models. Statistical models were analyzed using SPSS version 24.0 (IBM, New York, NY).

Main effects of adversity in childhood family environments and sex
There was a significant, negative effect of FES conflict (B = -.320; SE = .152; p = .037) on SBP which remained significant when adding current depressive affect (p = .041), but not when adding anxious affect and stress (ps > .05). Other aspects of the family environment were not associated with physiological outcomes (all ps > .10). Moreover, women had lower SBP (B = -9.856; SE = 1.310; p < .001), DBP (B = -3.314; SE = 1.042; p = .002) and total cortisol output (B = -.070; SE = .032; p = .032), but higher HR (B = 3.043; SE = 1.402; p = .031) than men. When including adult distress measures in the models, effects remained significant except when depressive affect was added to models for total cortisol output (ps > .05).

Interaction effects between adversity in childhood family environments and sex
Sex interacted with several measures of adversity in participants' childhood environments to predict adult physiological outcomes. Specifically, sex interacted with the RFQ and FES total as well as the FES conflict and FES cohesion subscales to predict SBP (Fig 1). Similarly, sex interacted with the FES total as well as the FES cohesion subscale to predict DBP (Fig 2). Marginal effects on DBP were additionally found for the interactions between sex and the RFQ and FES conflict subscale. Finally, participants' HR was only predicted by the sex X FES express interaction. Sex and early adversity did not interact to predict total salivary cortisol output. See Tables 2 and 3 for a detailed overview of these results. Notably, none of these results changed substantively when adding adult distress measures, with the one exception that the sex X FES total interaction dropped to marginal significance (B = -.183; SE = .095; p = .056) in the saturated model for DBP.
Next, separate models were fit for men and women to estimate simple slopes. Women who reported greater overall childhood adversity had lower SBP ( Additional, post-hoc sensitivity analyses adjusted for employment status, marital status and smoking status. This did not substantively alter results with the exception that the interaction between sex and FES expressiveness on HR dropped to marginal significance (B = -.739, SE = .376, p = .051). Early adversity, sex, and blood pressure

Discussion
This study adds to the literature suggesting that childhood adversity is differentially associated with physiological outcomes among men and women later in adulthood. We found that, among women only, greater childhood adversity was associated with lower levels of baseline BP (although not HR and salivary cortisol). Importantly, these results persisted even after taking into account a wide range of concurrent psychosocial risk factors (e.g., anxious and depressed affect) and relevant demographic covariates (e.g., marital status and employment status). When considering particular aspects of the childhood home environment, more conflictual and less cohesive environments were more clearly associated with BP in women than was expressiveness within the home.
Given that early adversity is associated with greater disease risk, including CVD, among women, the directionality of the current findings is counterintuitive and counter to our predictions. However, these associations were generally consistent across both SBP and DBP and across different measures of childhood adversity. Our findings are also in line with a recent study reporting a negative association between the number of endorsed adverse childhood events (ACEs) and resting SBP in the laboratory among a generally healthy, all-female sample [27]. Similarly, Su et al. [28], reported higher baseline DBP (but not SBP) among male and female adolescents and young adults who had reported experiencing 2+ ACEs; moderation of these findings by sex was not investigated. Our current findings suggest that among a nonclinical sample of generally healthy women, greater reported exposure to moderate severity childhood adversity may be associated with the opposite pattern of basal cardiovascular hypoactivation, perhaps suggesting a down-regulated sympathetic nervous system (SNS) response among women exposed to childhood adversity although the extent to which the SNS is involved in longer-term BP regulation is still unclear [29]. Alternatively, our findings may suggest a survival advantage among women who, despite experiencing early adversity, were deemed to be generally healthy and thus may represent a particularly high-functioning subgroup of individuals.
Strengths of this study include the thorough assessment of resting BP (averaged across three measurement sessions over the course of one day in the laboratory), multiple indicators of the childhood home environment, and a generally healthy, non-clinical sample of adult men and women. Nonetheless, participants' retrospective self-reports of their family home environment represents a limitation. Similarly, sex was self-reported; future research should tease apart the relative contributions of biological sex and socialized gender roles on the early adversity to BP connection. Lastly, this study was cross-sectional and the sample largely White. Thus, future research should investigate these associations in more diverse samples and examine potential mediating pathways, including individuals' health behaviors and coping strategies, and broader psychosocial circumstances. Similarly, the fact that the sample was recruited via newspaper advertisements represents a potential limitation. Given participant demographic characteristics, in particular average years of education and rates of unemployment, it appears unlikely that this method of recruitment biased the sample towards more educated or wealthier individuals. Nonetheless, it is possible that focusing on recruiting via newspaper Early adversity, sex, and blood pressure advertisements influenced the makeup of the sample in other ways. Finally, future research should investigate the possibility of three-way interaction effects between age, sex, and early adversity to inform our understanding of possible survivor effects if certain BP patterns are only apparent among older individuals, e.g., among older women exposed to greater early life adversity.
This study suggests that reporting exposure to moderate severity childhood adversity is associated with lower resting BP among healthy women, but not men, with potential implications for their long-term health. This is counter to some findings from clinical samples and further highlights the importance of separately considering effects of the early family environment on physiological health outcomes among men and women.