England Family Study Research Articles

Hypertension differentially impacts cognition in men and women in early midlife.

The current study aimed to understand how sex differences in the timing of hypertension onset contribute to early midlife risk for cognitive decline that may differ by sex and whether sex-dependent advantages in normotensive populations are influenced by the presence of hypertension. One hundred and ninety-five adults aged 45-55 from the New England Family Study underwent neuropsychological testing to assess attention, executive function, and memory. Physician-diagnosed hypertension status was self-reported via questionnaire. Mid-adulthood hypertension was associated with worse performance on measures of attention and memory, but the cognitive domains impacted varied by sex. Hypertension was associated with only attention in men, whereas in women it was associated with attention and associative and working memory. Sex differences in midlife cognitive performance found in normotensive adults were attenuated in those with hypertension. Our results underscore the importance of accounting for sex when assessing the impact of hypertension on midlife cognition that could be indicative of later decline and risk for cognitive impairment and dementia, given hypertension is an independent risk factor.

Infections During Pregnancy and Risks for Adult Psychosis: Findings from the New England Family Study.

For the past 40 years, our team has conducted a unique program of research investigating the prenatal risks for schizophrenia and related adult psychiatric disorders. The New England Family Study is a long-term prospective cohort study of over 16,000 individuals followed from the prenatal period for over 50 years. This chapter summarizes several major phases and findings from this work, highlighting recent results on maternal prenatal bacterial infections and brain imaging. Implications regarding the causes and potential prevention of major psychotic disorders are discussed.

Associations of types of green space across the life-course with blood pressure and body mass index

Green space has been associated with better health and well-being. However, most studies have been cross-sectional with limited long-term exposure data. Further, research is limited in what type of green space is beneficial for health. We conducted a longitudinal study to assess sensitive periods (birth, childhood or adulthood) of exposure to different types of green space in association with adult blood pressure and body mass index (BMI). Using longitudinal data from the New England Family Study (1960–2000) and multilevel regression analysis, we examined associations between time-varying markers of residential exposure to green space, and adult BMI, systolic (SBP) and diastolic blood pressure (DBP) (N = 517). We created three exposure metrics: distance, average area, and green space count in the neighborhood throughout the life-course. In adjusted models, living one mile farther away from a green space at birth was associated with a 5.6 mmHg higher adult SBP (95%CI: 0.7, 10.5), and 3.5 mmHg higher DBP (95%CI: 0.3, 6.8). One more green space in the neighborhood at birth was also associated with lower DBP (−0.2 mmHg, 95%CI: −0.4, −0.02) in adulthood. Finally, average area of green space was not associated with SBP, DBP nor BMI. Analysis by type of green space suggested that parks may be more relevant than playgrounds, cemeteries or golf courses. Our study suggests that the perinatal period may be a critical time-period where living closer to green spaces may lower hypertension risk in adulthood, but not obesity.

Longitudinal associations of neighborhood socioeconomic status with cardiovascular risk factors: A 46-year follow-up study

ObjectivesNeighborhood characteristics are increasingly recognized as important determinants of cardiovascular disease (CVD) risk. However, longitudinal studies on the health impacts of neighborhood characteristics are rare. We sought to investigate whether neighborhood socioeconomic status (NSES) during birth, childhood and adulthood is associated with CVD risk factors in adulthood. MethodsUsing longitudinal data from the New England Family Study (n = 671) with 46-years of follow-up, participants' home addresses were geocoded at birth (mean age = 1.6 months), childhood (mean age = 7.1 years), and adulthood (mean age = 44.2 years) across Massachusetts and Rhode Island in the US from 1961 to 2007. We used multilevel models to evaluate associations of NSES across the life-course with systolic blood pressure, diastolic blood pressure and body mass index (BMI) in adulthood, adjusting for age, sex, race/ethnicity, mother's race, individual SES, and parental SES. ResultsIn fully adjusted models, one standard deviation higher NSES at birth was associated with a 1.9 mmHg lower SBP (95% CI: 3.8, −0.1) and 1.3 mmHg lower DBP (95%CI: 2.6,-0.03) in adulthood; while one standard deviation of higher NSES at adulthood was associated with 0.87 kg/m2 lower BMI (95%CI: 1.7, −0.1). ConclusionsWe found that living in a socioeconomically disadvantaged neighborhood early in life and in adulthood was associated with blood pressure and BMI, respectively, two established risk factors for CVD. Our findings support a longitudinal association between exposure to socioeconomically disadvantaged neighborhoods in early life and CVD risk factors in adulthood.

Impact of sex and reproductive status on memory circuitry structure and function in early midlife using structural covariance analysis

Research on age-related memory alterations traditionally targets individuals aged ≥65 years. However, recent studies emphasize the importance of early aging processes. We therefore aimed to characterize variation in brain gray matter structure in early midlife as a function of sex and menopausal status. Subjects included 94 women (33 premenopausal, 29 perimenopausal, and 32 postmenopausal) and 99 demographically comparable men from the New England Family Study. Subjects were scanned with a high-resolution T1 sequence on a 3 T whole body scanner. Sex and reproductive-dependent structural differences were evaluated using Box's M test and analysis of covariances (ANCOVAs) for gray matter volumes. Brain regions of interest included dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (iPAR), anterior cingulate cortex (ACC), hippocampus (HIPP), and parahippocampus. While we observed expected significant sex differences in volume of hippocampus with women of all groups having higher volumes than men relative to cerebrum size, we also found significant differences in the covariance matrices of perimenopausal women compared with postmenopausal women. Associations between ACC and HIPP/iPAR/DLPFC were higher in postmenopausal women and correlated with better memory performance. Findings in this study underscore the importance of sex and reproductive status in early midlife for understanding memory function with aging.

The Internet Addiction Test in a Young Adult U.S. Population.

Internet use has increased rapidly over the past 20 years, accompanied by a growing number of individuals whose Internet use has adverse effects on their lives. Yet no study to date has administered the Young's Internet Addiction Test (IAT) in the United States, nor has the reliability been assessed in a U.S. population. Thus, we aimed to: (a) assess the reliability of the instrument and (b) examine sociodemographic characteristics associated with the Internet addiction score. Participants included young adults 21-28 years of age, the third generation of a 50-year longitudinal cohort, the New England Family Study. The mean weighted kappa across all 20 items of the instrument was 0.45 and the median was 0.46. To examine correlates of the addiction score, we examined age, gender, race/ethnicity, education, partnership status, employment, social support, and depression diagnosis. In the fully adjusted model, those with social support had -3.96 (95% CI: -6.52 to -1.41) lower Internet addiction scores on average compared to those without social support. Also, those with a depression diagnosis had 3.28 (95% confidence interval [CI]: 1.03-5.84) higher Internet addiction scores on average compared to those without a depression diagnosis. Study findings suggest that Young's IAT had good reliability in a U.S. young adult population. Therefore, this measure can be a useful tool to measure Internet addiction in young adult populations in the United States. Future studies should examine the potential benefits of social support and depression treatment in Internet addiction among young adults in the United States.

Gestational cytokine concentrations and neurocognitive development at 7 years

Gestational inflammation may contribute to brain abnormalities associated with childhood neuropsychiatric disorders. Limited knowledge exists regarding the associations of maternal cytokine levels during pregnancy with offspring neurocognitive development. We assayed the concentrations of five cytokines (interleukin (IL)-6, IL-1β, IL-8, tumor necrosis factor alpha (TNF-α), and IL-10) up to four times in the 2nd and 3rd trimesters of pregnancy using stored prenatal sera from 1366 participants in the New England Family Study (enrollment 1959–1966). Intelligence (IQ), academic achievement, and neuropsychological functioning of singleton offspring were assessed at age 7 years using standardized tests. We used linear mixed models with random effects to estimate the cumulative exposure to each cytokine during 2nd and 3rd trimesters, and then related cumulative cytokine exposure to a wide range of offspring neurocognitive outcomes. We found that children of women with higher levels of the pro-inflammatory cytokine, TNF-α, in the 2nd and 3rd trimesters had lower IQ (B = −2.51, 99% CI: −4.84,−0.18), higher problem scores in visual-motor maturity (B = 0.12, 99% CI: 0.001,0.24), and lower Draw-a-Person test scores (B = −1.28, 99% CI: −2.49,−0.07). Higher gestational levels of IL-8, another pro-inflammatory molecule, were associated with better Draw-a-Person test scores and tactile finger recognition scores. Other cytokines were not associated with our outcome of interest. The opposing directions of associations observed between TNF-α and IL-8 with childhood outcomes suggest pleiotropic effects of gestational inflammation across the domains of neurocognitive functioning. Although the path to psychopathological disturbances in children is no doubt multifactorial, our findings point to a potential role for immune processes in the neurocognitive development of children.

Socioeconomic disadvantage, gestational immune activity, and neurodevelopment in early childhood

Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting that inequalities in health have early origins. From the child's perspective, exposure to economic hardship may begin as early as conception, potentially via maternal neuroendocrine-immune responses to prenatal stressors, which adversely impact neurodevelopment. Here we investigate whether socioeconomic disadvantage is associated with gestational immune activity and whether such activity is associated with abnormalities among offspring during infancy. We analyzed concentrations of five immune markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in maternal serum from 1,494 participants in the New England Family Study in relation to the level of maternal socioeconomic disadvantage and their involvement in offspring neurologic abnormalities at 4 mo and 1 y of age. Median concentrations of IL-8 were lower in the most disadvantaged pregnancies [-1.53 log(pg/mL); 95% CI: -1.81, -1.25]. Offspring of these pregnancies had significantly higher risk of neurologic abnormalities at 4 mo [odds ratio (OR) = 4.61; CI = 2.84, 7.48] and 1 y (OR = 2.05; CI = 1.08, 3.90). This higher risk was accounted for in part by fetal exposure to lower maternal IL-8, which also predicted higher risks of neurologic abnormalities at 4 mo (OR = 7.67; CI = 4.05, 14.49) and 1 y (OR = 2.92; CI = 1.46, 5.87). Findings support the role of maternal immune activity in fetal neurodevelopment, exacerbated in part by socioeconomic disadvantage. This finding reveals a potential pathophysiologic pathway involved in the intergenerational transmission of socioeconomic inequalities in health.

The interplay of childhood behavior problems and IQ in the development of later schizophrenia and affective psychoses

Schizophrenia and affective psychoses are both associated with impaired social functioning, but the extent to which childhood behavioral impairments are present prior to onset of illness is less well studied. Moreover, the concurrent relationship of childhood behavior problems and premorbid IQ with subsequent psychotic disorder has not been established. We investigated whether childhood behavior problems are associated with increased risk for adult schizophrenia or affective psychosis, independently and in combination with IQ. The study included individuals with schizophrenia (N=47), affective psychoses (N=45) and non-psychotic controls (N=1496) from the New England Family Study. Behavior problems were prospectively assessed from standardized clinician observations at ages 4 and 7. IQ was assessed with the Stanford-Binet at age 4 and the Wechsler Intelligence Scale for Children at age 7. We found externalizing problems at age 4 and externalizing and internalizing problems at age 7 were associated with later schizophrenia, and both internalizing and externalizing problems at ages 4 and 7 were associated with later development of affective psychoses. Lower IQ at ages 4 and 7 was associated with schizophrenia, while lower IQ was associated with affective psychoses at age 7 only. Examined simultaneously, both lower IQ and behavior problems remained associated with risk of schizophrenia, while only behavior problems remained associated with affective psychoses. Behavior problems appear to be a general marker of risk of adult psychotic disorder, while lower childhood IQ is more specific to risk of schizophrenia. Future research should clarify the premorbid evolution of behavior and cognitive problems into adult psychosis.

Epigenetic Mediators Between Childhood Socioeconomic Disadvantage and Mid-Life Body Mass Index: The New England Family Study.

Childhood socioeconomic disadvantage is associated with adulthood obesity risk; however, epigenetic mechanisms are poorly understood. This work's objective was to evaluate whether associations of childhood socioeconomic disadvantage with adulthood body mass index (BMI) are mediated by DNA methylation. Participants were 141 men and women from the New England Family Study, prospectively followed prenatally through a mean age of 47 years. Epigenomewide DNA methylation was evaluated in peripheral blood and adipose tissue obtained at adulthood, using the Infinium HumanMethylation450K BeadChip. Childhood socioeconomic status (SES) at age 7 years was assessed directly from parents' reports. Offspring adiposity was directly assessed using BMI at a mean age of 47 years. Associations of SES, DNA methylation, and BMI were estimated using least square estimators. Statistical mediation analyses were performed using joint significance test and bootstrapping. Of CpG sites significant at the 25% false discovery rate level in epigenomewide methylation BMI analyses, 91 sites in men and 71 sites in women were additionally significant for SES-methylation associations (p < .001) in adipose tissue. Many involved genes biologically relevant for development of obesity, including fatty acid synthase, transmembrane protein 88, signal transducer and activator of transcription 3, and neuritin 1. There was no evidence of epigenetic mediation in peripheral blood leukocytes. DNA methylation at specific genes may be mediators of associations between childhood socioeconomic disadvantage and mid-life BMI in adipose tissue. Findings motivate continued efforts to study if and how childhood socioeconomic disadvantage is biologically embedded at the level of the epigenome in regions etiologically relevant for adiposity.

Prenatal immune programming of the sex-dependent risk for major depression.

Maternal immune functioning during pregnancy contributes to sex-dependent deficits in neurodevelopment and to behaviors associated with affective traits in preclinical studies, and has been indirectly associated with offspring depression in epidemiologic studies. We therefore investigated the association between immune activity during pregnancy and the risk of depression among male and female offspring. We conducted a case–control study of depression (n=484 cases and n=774 controls) using data from the New England Family Study, a pregnancy cohort enrolled between 1959 and 1966 that assessed psychiatric outcomes in adult offspring (mean age=39.7 years). We assayed concentrations of three pro-inflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokine, IL-10, in maternal serum collected at the end of the second and beginning of the third trimesters. High maternal TNF-α was associated with reduced odds of depression among both male and female offspring (odds ratio (OR)=0.68; confidence interval (CI)=0.48, 0.98). However, when considering the TNF-α to IL-10 ratio, a measure of the ratio of pro- to anti-inflammatory loading, maternal immune effects on offspring depression differed significantly by sex (χ2=13.9, degrees of freedom=4, P=0.008). Among females, higher maternal TNF-α:IL-10 was associated with reduced odds of depression (OR=0.51; CI=0.32, 0.81), whereas, among males, high maternal TNF-α:IL-10 was associated with elevated odds of depression (OR=1.86; CI=1.02, 3.39). Thus, the balance between TNF-α and IL-10 in maternal prenatal serum was associated with depression in a sex-dependent manner. These findings are consistent with the role of TNF-α in the maturation of the sexually dimorphic fetal brain circuitry that regulates stress and affective responses, and support a prenatal stress-immune model of depression pathogenesis.

Associations of Mindfulness with Glucose Regulation and Diabetes.

To evaluate whether dispositional mindfulness is associated with glucose regulation and type 2 diabetes. Study participants (N = 399) were from the New England Family Study, a prospective birth cohort, with median age 47 years. Dispositional mindfulness was assessed using the Mindful Attention Awareness Scale (MAAS). Type 2 diabetes and "normal plasma glucose" were defined using American Diabetes Association criteria. Multivariable-adjusted regression analyses demonstrated that participants with high versus low MAAS scores were significantly more likely to have normal plasma glucose levels (prevalence ratio = 1.35 (95% confidence interval (CI): 1.08,1.87)), and were not significantly associated with type 2 diabetes (prevalence ratio = 0.83, 95% CI: 0.38,1.79), adjusted for age, sex, race/ethnicity, family history of diabetes and childhood socioeconomic status. Mediation analyses provided evidence of mediation via obesity and sense of control, where indirect effects were prevalence ratios (95% CI) of 1.03 (1.00,1.10) and 1.08 (1.00,1.21), respectively. Dispositional mindfulness may be associated with better glucose regulation, in part because of a lower likelihood of obesity and greater sense of control among participants with higher levels of mindfulness. These findings need to be replicated by prospective studies to establish causality and to evaluate potential implications for mindfulness-based interventions to reduce risk of type 2 diabetes.

Early childhood social disadvantage is associated with poor health behaviours in adulthood

Background: Individual health behaviours are considered important risk factors for cardiometabolic diseases. These behaviours may be socially patterned by early exposure to social disadvantage, but few studies have prospectively tested this hypothesis empirically.Aim: This study investigated whether childhood social disadvantage was associated with likelihood of engaging in less healthy behaviours 40 years later.Subjects and methods: Prospective data were analysed from the New England Family Study, a 2005–2007 adult follow-up of a cohort initiated in 1959–1966 (n = 565). Childhood social environment (age 7 years) was assessed using a cumulative index of socioeconomic and family stability factors. Logistic regression models evaluated associations between social disadvantage and each health-related behaviour and obesity in adulthood.Results: Relative to low disadvantage, higher disadvantage was associated with 3.6-fold greater odds of smoking (95% CI = 1.9–7.0), 4.8-fold greater odds (in women only) of excess alcohol consumption (95% CI = 1.6–14.2) and 2.7-fold greater odds of obesity (95% CI = 1.3–5.5), but was not associated with unhealthy diet or physical inactivity.Conclusion: These findings suggest childhood social disadvantage may contribute to adult cardiometabolic disease by predisposing children to adopt certain unhealthy behaviours. If replicated, such findings may support intervention strategies that target social environmental factors and behavioural pathways that are established early in life.

Associations of Dispositional Mindfulness with Obesity and Central Adiposity: the New England Family Study.

To evaluate whether dispositional mindfulness (defined as the ability to attend nonjudgmentally to one's own physical and mental processes) is associated with obesity and central adiposity. Study participants (n = 394) were from the New England Family Study, a prospective birth cohort, with median age 47 years. Dispositional mindfulness was assessed using the Mindful Attention Awareness Scale (MAAS). Central adiposity was assessed using dual-energy X-ray absorptiometry (DXA) scans with primary outcomes android fat mass and android/gynoid ratio. Obesity was defined as body mass index ≥30 kg/m(2). Multivariable-adjusted regression analyses demonstrated that participants with low vs. high MAAS scores were more likely to be obese (prevalence ratio for obesity = 1.34 (95 % confidence limit (CL): 1.02, 1.77)), adjusted for age, gender, race/ethnicity, birth weight, childhood socioeconomic status, and childhood intelligence. Furthermore, participants with low vs. high MAAS level had a 448 (95 % CL 39, 857) g higher android fat mass and a 0.056 (95 % CL 0.003, 0.110) greater android/gynoid fat mass ratio. Prospective analyses demonstrated that participants who were not obese in childhood and became obese in adulthood (n = 154) had -0.21 (95 % CL -0.41, -0.01; p = 0.04) lower MAAS scores than participants who were not obese in childhood or adulthood (n = 203). Dispositional mindfulness may be inversely associated with obesity and adiposity. Replication studies are needed to adequately establish whether low dispositional mindfulness is a risk factor for obesity and adiposity.

Elevated risk of nicotine dependence among sib-pairs discordant for maternal smoking during pregnancy: evidence from a 40-year longitudinal study.

Compelling evidence links maternal smoking during pregnancy with elevated risk of nicotine dependence among the offspring. However, no study to date has examined the maternal smoking during pregnancy-nicotine dependence link among sibling-pairs discordant for maternal smoking during pregnancy. We tested two hypotheses that, if supported, suggest that the maternal smoking during pregnancy-nicotine dependence link may be physiologically mediated. Study participants were adult offspring of women enrolled in the Providence and Boston sites of the Collaborative Perinatal Project (1959-1966). Approximately 10% of these adult offspring (average age: 39.6 years) were enrolled in the New England Family Study (n = 1,783), a follow-up study that oversampled families with multiple siblings. Logistic regression models predicting maternal smoking during pregnancy risk on various prospectively collected smoking and marijuana use outcomes, including nicotine dependence, were fit using models that allowed between-mother effects of maternal smoking during pregnancy exposure to differ from within-mother effects. In the absence of significant effect heterogeneity, we calculated a combined estimate. Maternal smoking during pregnancy predicted progression from weekly smoking to nicotine dependence (odds ratio = 1.4 [95% confidence interval = 1.2, 1.8]), but not weekly smoking or progression to marijuana dependence. Current evidence from sibling-pairs discordant for maternal smoking during pregnancy is consistent with previous reports of a dose-response association between maternal smoking during pregnancy and nicotine dependence, as well as of up-regulation of nicotine receptors among animals exposed to maternal smoking during pregnancy. Together, they provide support for the existence of a physiologically mediated link between maternal smoking during pregnancy and nicotine dependence.

Prospective Evaluation of Associations Between Prenatal Cortisol and Adulthood Coronary Heart Disease Risk

Increasing evidence suggests that early life factors may influence coronary heart disease (CHD) risk; however, little is known about the contributions of prenatal cortisol. Objectives were to prospectively assess the associations of maternal cortisol levels during pregnancy with offspring's 10-year CHD risk during middle age. Participants were 262 mother-offspring dyads from the New England Family Study. Maternal free cortisol was assessed in third-trimester maternal serum samples. Ten-year CHD risk was calculated in offspring at a mean age of 42 years, using the validated Framingham risk algorithm incorporating diabetes, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol, smoking, age, and sex. In multivariable-adjusted linear regression analyses adjusted for age and race/ethnicity, high versus low maternal cortisol tertile was associated with 36.7% (95% confidence interval [CI] = 8.4% to 72.5%) greater mean 10-year CHD risk score in women. There was no association in men (-2.8%, 95% CI = -23.8% to 24.0%). Further adjustment for in utero socioeconomic position showed 26.1% (95% CI = -0.5% to 59.9%) greater CHD risk in women. Adjustment for maternal age and size for gestational age had little effect on findings. Maternal prenatal cortisol levels were positively associated with 10-year CHD risk among female, and not male, offspring. Adjusting for socioeconomic position during pregnancy reduced effect size in women, suggesting that it may be a common prior factor in both maternal cortisol and CHD risk. These findings provide evidence that targeting mothers who have elevated prenatal cortisol levels, including elevated cortisol in the setting of low socioeconomic position, may potentially reduce long-term CHD risk in their offspring.

Adiposity is associated with DNA methylation profile in adipose tissue.

Adiposity is a risk factor for type 2 diabetes and cardiovascular disease, suggesting an important role for adipose tissue in the development of these conditions. The epigenetic underpinnings of adiposity are not well understood, and studies of DNA methylation in relation to adiposity have rarely focused on target adipose tissue. Objectives were to evaluate whether genome-wide DNA methylation profiles in subcutaneous adipose tissue and peripheral blood leukocytes are associated with measures of adiposity, including central fat mass, body fat distribution and body mass index. Participants were 106 men and women (mean age 47 years) from the New England Family Study. DNA methylation was evaluated using the Infinium HumanMethylation450K BeadChip. Adiposity phenotypes included dual-energy X-ray absorptiometry-assessed android fat mass, android:gynoid fat ratio and trunk:limb fat ratio, as well as body mass index. Adipose tissue genome-wide DNA methylation profiles were associated with all four adiposity phenotypes, after adjusting for race, sex and current smoking (omnibus p-values <0.001). After further adjustment for adipose cell-mixture effects, associations with android fat mass, android:gynoid fat ratio, and trunk:limb fat ratio remained. In gene-specific analyses, adiposity phenotypes were associated with adipose tissue DNA methylation in several genes that are biologically relevant to the development of adiposity, such as AOC3, LIPE, SOD3, AQP7 and CETP. Blood DNA methylation profiles were not associated with adiposity, before or after adjustment for blood leukocyte cell mixture effects. Findings show that DNA methylation patterns in adipose tissue are associated with adiposity.

Education and coronary heart disease risk: potential mechanisms such as literacy, perceived constraints, and depressive symptoms.

Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. The study sample included 346 participants, aged 38 to 47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, high-density lipoprotein cholesterol, age, and gender. Multivariable regression and mediation analyses were performed. Regression analyses adjusting for age, race/ethnicity, and childhood confounders (e.g., parental socioeconomic status, intelligence) demonstrated that relative to those with greater than or equal to college education, men and women with less than high school had 73.7% (95% confidence interval [CI; 29.5, 133.0]) and 48.2% (95% CI [17.5, 86.8]) higher 10-year CHD risk, respectively. Mediation analyses demonstrated significant indirect effects for reading comprehension in women (7.2%; 95% CI [0.7, 19.4]) and men (7.2%; 95% CI [0.8, 19.1]), and depressive symptoms (11.8%; 95% CI [2.5, 26.6]) and perceived constraint (6.7%, 95% CI [0.7, 19.1]) in women. Evidence suggested that reading comprehension in women and men, and depressive symptoms and perceived constraint in women, may mediate some of the association between education and CHD risk. If these mediated effects are interpreted causally, interventions targeting reading, depressive symptoms, and perceived constraint could reduce educational inequalities in CHD.

Positive Associations of Dispositional Mindfulness with Cardiovascular Health: the New England Family Study.

Mindfulness (the ability to attend nonjudgmentally to one's own physical and mental processes) is receiving substantial interest as a potential determinant of health. However, little is known whether mindfulness is associated with cardiovascular health. The aim of this study is to evaluate whether dispositional mindfulness is associated with cardiovascular health. Study participants (n = 382) were from the New England Family Study, born in Providence, RI, USA, with mean age 47 years. Dispositional mindfulness was assessed using the Mindful Attention Awareness Scale (MAAS). Cardiovascular health was assessed based on American Heart Association criteria. Cross-sectional multivariable-adjusted log binomial regression analyses were performed. Analyses demonstrated that those with high vs. low MAAS had prevalence ratio (PR) for good cardiovascular health of 1.83 (95 % confidence interval (CI) 1.07, 3.13), adjusted for age, gender, and race/ethnicity. There were significant associations of high vs. low mindfulness with nonsmoking (PR = 1.37, 95 % CI 1.06, 1.76), body mass index <25 kg/m(2) (PR = 2.17, 95 % CI 1.16, 4.07), fasting glucose <100 mg/dL (PR = 1.47, 95 % CI 1.06, 2.04), and high physical activity (PR = 1.56, 95 % CI 1.04, 2.35), but not blood pressure, total cholesterol, or fruit/vegetable consumption. Exploratory mediation analyses suggested that sense of control and depressive symptomatology may be mediators. This study demonstrated preliminary cross-sectional evidence that dispositional mindfulness is positively associated with cardiovascular health, with the associations particularly driven by smoking, body mass index, fasting glucose, and physical activity. If in future research mindfulness-based practices are found to consistently improve cardiovascular disease risk factors, such interventions may have potential to strengthen effects of cardiovascular health promotion programs.

17β-estradiol differentially regulates stress circuitry activity in healthy and depressed women.

Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β-estradiol (E₂) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E₂ during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E₂ conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E₂ modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E₂ conditions were attenuated under high E₂ conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk.