Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.

The social environment plays a considerable role in determining major psychiatric disorders. Emerging evidence suggests that features of the social environment modify gene expression independently of the primary DNA sequence through epigenetic processes. Accordingly, dysfunction of epigenetic mechanisms offers a plausible mechanism by which an adverse social environment gets “into the mind” and results in poor mental health. The purpose of this review is to provide an overview of the studies suggesting that epigenetic changes introduced by the social environment then manifest as psychological consequences. Our goal is to build a platform to discuss the ways in which future epidemiologic studies may benefit from including epigenetic measures. We focus on schizophrenia, major depressive disorder, post-traumatic stress disorder, anorexia nervosa, and substance dependence as examples that highlight the ways in which social environmental exposures, mediated through epigenetic processes, affect mental health.

Food insecurity (which can be defined as inadequate access to sufficient, safe, and nutritious food that meets individuals’ dietary needs) is concurrently associated with children’s psychological difficulties. However, the predictive role of food insecurity with regard to specific types of children’s mental health symptoms has not previously been studied. We used data from the Longitudinal Study of Child Development in Québec, LSCDQ, a representative birth cohort study of children born in the Québec region, in Canada, in 1997–1998 (n = 2120). Family food insecurity was ascertained when children were 1½ and 4½ years old. Children’s mental health symptoms were assessed longitudinally using validated measures of behaviour at ages 4½, 5, 6 and 8 years. Symptom trajectory groups were estimated to identify children with persistently high levels of depression/anxiety (21.0%), aggression (26.2%), and hyperactivity/inattention (6.0%). The prevalence of food insecurity in the study was 5.9%. In sex-adjusted analyses, children from food-insecure families were disproportionately likely to experience persistent symptoms of depression/anxiety (OR: 1.79, 95% CI 1.15–2.79) and hyperactivity/inattention (OR: 3.06, 95% CI 1.68–5.55). After controlling for immigrant status, family structure, maternal age at child’s birth, family income, maternal and paternal education, prenatal tobacco exposure, maternal and paternal depression and negative parenting, only persistent hyperactivity/inattention remained associated with food insecurity (fully adjusted OR: 2.65, 95% CI 1.16–6.06). Family food insecurity predicts high levels of children’s mental health symptoms, particularly hyperactivity/inattention. Addressing food insecurity and associated problems in families could help reduce the burden of mental health problems in children and reduce social inequalities in development.

Background

Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (“nature”) and environments (“nurture”) are important for understanding the etiology of depression has led to rapid growth in research exploring gene–environment interactions (GxE). However, there has been no systematic review of GxE in youth depression to date.

Methods

The goal of this article was to systematically review evidence on the contribution of GxE to the risk of child and adolescent depression. Though a search of PubMed and PsycINFO databases to 1 April 2010, we identified 20 candidate gene–environment interaction studies focused on depression in youth (up to age 26) and compared each study in terms of the following characteristics: research design and sample studied; measure of depression and environment used; genes explored; and GxE findings in relation to these factors.

Results

In total 80% of studies (n=16) found at least one significant GxE association. However, there was wide variation in methods and analyses adopted across studies, especially with respect to environmental measures used and tests conducted to estimate GxE. This heterogeneity made it difficult to compare findings and evaluate the strength of the evidence for GxE.

Conclusions

The existing body of GxE research on depression in youth contains studies that are conceptually and methodologically quite different, which contributes to mixed findings and makes it difficult to assess the current state of the evidence. To decrease this heterogeneity, we offer 20 recommendations that are focused on: (1) reporting GxE research; (2) testing and reporting GxE effects; (3) conceptualizing, measuring, and analyzing depression; (4) conceptualizing measuring, and analyzing environment; (5) increasing power to test for GxE; and (6) improving the quality of genetic data used. Although targeted to GxE research on depression, these recommendations can be adopted by GxE researchers focusing on other mental health outcomes.

Background

Asthma has the potential to adversely affect children's school examination performance, and hence longer term life chances. Asthma morbidity is especially high amongst UK ethnic minority children and those experiencing social adversity, populations which also have poor educational outcomes. We tested the hypothesis that asthma adversely affects performance in national school examinations in a large cohort from an area of ethnic diversity and social deprivation.

Methods and Findings

With a novel method (using patient and address-matching algorithms) we linked administrative and clinical data for 2002–2005 for children in east London aged 5–14 years to contemporaneous education and social care datasets. We modelled children's performance in school examinations in relation to socio-demographic and clinical variables.

The dataset captured examination performance for 12,136 children who sat at least one national examination at Key Stages 1–3. For illustration, estimates are presented as percentage changes in Key Stage 2 results. Having asthma was associated with a 1.1% increase in examination scores (95%CI 0.4 to 1.7)%,p = 0.02. Worse scores were associated with Bangladeshi ethnicity −1.3%(−2.5 to −0.1)%,p = 0.03; special educational need −14.6%(−15.7 to −13.5)%,p = 0.02; mental health problems −2.5%(−4.1 to −0.9)%,p = 0.003, and social adversity: living in a smoking household −1.2(−1.7 to −0.6)%,p<0.001; living in social housing −0.8%(−1.3 to −0.2)% p = 0.01, and entitlement to free school meals −0.8%(−1.5 to −0.1)%,p<0.001.

Conclusions

Social adversity and ethnicity, but not asthma, are associated with poorer performance in national school examinations. Policies to improve educational attainment in socially deprived areas should focus on these factors.

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Objectives

To compare stress levels among residents in large Chinese cities between 2001 and 2008.

Methods

Survey data were collected in three mainland Chinese capital cities in two waves, in 2001 and 2008, respectively. Participants were recruited through a multi-stage stratified sampling process. Stress was assessed using the Perceived Stress Scale, Chinese version (CPSS). Descriptive methods were used to estimate mean stress levels and associated 95% confidence intervals. Estimates were adjusted by post-stratification weights.

Results

Indicating stable stress levels, respective adjusted mean stress scores for the combined samples of study participants were 23.90 (95%CI: 23.68–24.12) in 2001 and 23.69 (95%CI: 23.38–24.01) in 2008. A lower stress level in 2008 than in 2001 manifested among residents who were under 25 years of age; female; with a college or higher level education; divorced, widowed, or separated; members of the managerial and clerical group; students or army personnel; or with an annual income of at least 30,000 RMB.

Conclusion

The overall stress level did not change among the combined sample of residents in the three Chinese study cities between 2001 and 2008. However, levels remained high and varied across social strata, and may have reflected a national trend among urban residents. Findings indicate a need for a new health policy, and call for the design and implementation of evidence-based interventions that target the highest-risk groups.

With the advent of specialized television channels offering 24-hour coverage, Internet and smart phones, the possibility to be constantly in contact with the media has increased dramatically in the last decades. Despite this higher access to knowledge, the impact media exposure has on healthy individuals remains poorly studied. Given that most information conveyed in the media is negative and that upon perception of threat, the brain activates the stress system, which leads to cortisol secretion, we decided to determine how healthy individuals react to media information. Accordingly, we investigated whether reading real negative news (1) is physiologically stressful, (2) modulates one’s propensity to be stress reactive to a subsequent stressor and (3) modulates remembrance for these news. Sixty participants (30 women, 30 men) were randomly assigned to either twenty-four real neutral news excerpts or to twenty-four real negative excerpts for 10 minutes. They were then all exposed to a well-validated psychosocial stressor, the Trier Social Stress Test (TSST), which consists of an anticipation phase of 10 minutes and a test phase of 10 minutes. A total of eight salivary cortisol samples were collected, at 10-minutes intervals, throughout the experimental procedure. One day later, a free recall of the news was performed. Results showed that although reading negative news did not lead to change in cortisol levels (p>0.05), it led to a significant increase in cortisol to a subsequent stressor in women only (p<0.001). Also, women in the negative news condition experienced better memory for these news excerpts compared to men (p<0.01). These results suggest a potential mechanism by which media exposure could increase stress reactivity and memory for negative news in women.

Background

We focused on whether changes in the occupational status of older male adults can be influenced by social engagement and health status measured at the baseline.

Methods

This study used a sample of the Korean Longitudinal Study of Aging (KLoSA), and the study population was restricted to 1.531 men who were aged 55 to 80 years at the 2006 baseline survey and participated in the second survey in 2008. Social engagement and health status, measured by the number of chronic diseases, grip strength, and depressive symptoms as well as covariates (age, marital status, educational level, and household income) were based on data from the 2006 baseline survey. Occupational engagement over the first and second survey was divided into four categories: ‘consistently employed’ (n = 892), ‘employed-unemployed’ (n = 152), ‘unemployed-employed’ (n = 138), and ‘consistently unemployed’ (n = 349).

Results

In the multinomial model, the ‘consistently employed’ and ‘unemployed-employed’ groups had significantly higher social engagement (1.19 and 1.32 times, respectively) than the referent. The number of chronic diseases was significantly associated with four occupational changes, and the ‘unemployed-employed’ had the fewest chronic conditions.

Conclusion

Our finding suggests that social engagement and health status are likely to affect opportunities to continue working or to start working for older male adults.

Purpose

Emerging work suggests that both environmental and genetic factors contribute to risk of depression in adolescents, and that these factors may differ between genders. We assessed whether features of the social environment (SE), measured at varying levels, and genetic factors jointly shape the risk of depression in adolescent males and females.

Methods

Using data from a national survey of U.S. adolescents, we applied cross-sectional, multilevel mixed models to assess the contribution of: (i) 5-HTTLPR genotype and respondent-level building conditions to depressive sympton score (DSS); and (ii) 5-HTTLPR genotype and neighborhood-level building conditions to DSS. Models testing potential gene-SE (G × SE) interactions were also conducted. All models were stratified by gender and adjusted for age, race/ethnicity, family structure, parental education and social support.

Results

Among females, adjusted analyses indicated that sl genotype carriers enjoyed a marginally significant (p=0.07) protective effect against higher DSS in models assessing respondent-level building conditions. In contrast, among males, adjusted analyses predicted significantly higher DSS for residents of neighborhoods with relatively poor building conditions (p<0.01). No significant G X SE interactions were detected for either gender.

Conclusions

These results suggest that adverse, macro-level SE effects increase risk of depression to a greater extent in adolescent males than females. Intervention strategies designed to improve mental health in adolescent populations should consider a growing body of work suggesting that the contextual effects conferring increased risk of depression differ among males and females.

Children of depressed mothers have impaired cognitive, behavioral, and health outcomes from infancy through adulthood, and are especially at risk when maternal depression persists over multiple years. But there are several important limitations to our current descriptive knowledge about maternal depression, especially depression among unmarried mothers. Data from the Fragile Families and Child Wellbeing Study, a recent cohort of children born in urban areas to mostly unmarried parents (N = 4,366), was used to examine the prevalence and correlates of maternal depression when children were about 1, 3, 5, and 9 years old. Results show that, at any given survey wave, between 16% and 21% of mothers reported depression. Nearly two-fifths (38%) of mothers reported depression at least once during the eight-year period, and 7% reported persistent depression (depression at three or four of the four survey waves). Employment status, relationship status, and fathers’ depression were among the sociodemographic characteristics most robustly associated with both stability and change in maternal depression. Given the important social consequences of maternal depression, not least of which is impaired wellbeing among children of depressed mothers, prevention and treatment of maternal depression should be an imperative for researchers, clinicians, and policymakers alike.

Background

International humanitarian aid workers providing care in emergencies are subjected to numerous chronic and traumatic stressors.

Objectives

To examine consequences of such experiences on aid workers' mental health and how the impact is influenced by moderating variables.

Methodology

We conducted a longitudinal study in a sample of international non-governmental organizations. Study outcomes included anxiety, depression, burnout, and life and job satisfaction. We performed bivariate regression analyses at three time points. We fitted generalized estimating equation multivariable regression models for the longitudinal analyses.

Results

Study participants from 19 NGOs were assessed at three time points: 212 participated at pre-deployment; 169 (80%) post-deployment; and 154 (73%) within 3–6 months after deployment. Prior to deployment, 12 (3.8%) participants reported anxiety symptoms, compared to 20 (11.8%) at post-deployment (p = 0·0027); 22 (10.4%) reported depression symptoms, compared to 33 (19.5%) at post-deployment (p = 0·0117) and 31 (20.1%) at follow-up (p = .00083). History of mental illness (adjusted odds ratio [AOR] 4.2; 95% confidence interval [CI] 1·45–12·50) contributed to an increased risk for anxiety. The experience of extraordinary stress was a contributor to increased risk for burnout depersonalization (AOR 1.5; 95% CI 1.17–1.83). Higher levels of chronic stress exposure during deployment were contributors to an increased risk for depression (AOR 1·1; 95% CI 1·02–1.20) comparing post- versus pre-deployment, and increased risk for burnout emotional exhaustion (AOR 1.1; 95% CI 1.04–1.19). Social support was associated with lower levels of depression (AOR 0·9; 95% CI 0·84–0·95), psychological distress (AOR = 0.9; [CI] 0.85–0.97), burnout lack of personal accomplishment (AOR 0·95; 95% CI 0·91–0·98), and greater life satisfaction (p = 0.0213).

Conclusions

When recruiting and preparing aid workers for deployment, organizations should consider history of mental illness and take steps to decrease chronic stressors, and strengthen social support networks.

Background

Post-traumatic stress disorder (PTSD) is an anxiety disorder that not only affects mental health, but may also affect bone health. However, there have been no studies to examine the direct relationship between PTSD and bone.

Methodology/Principal Findings

We employed electric shocks in mice to simulate traumatic events that cause PTSD. We also injected the anxiogenic drug FG-7142 prior to electric shocks. Electric shocks created lasting conditioned fear memory in all mice. In young mice, electric shocks elicited not only behavioral response but also skeletal response, and injection of FG-7142 appeared to increase both types of response. For example in behavioral response within the first week, mice shocked alone froze an average of 6.2 sec in 10 sec tests, and mice injected with FG-7142 froze 7.6 sec, both significantly different (P<0.05) from control mice, which only froze 1.3 sec. In skeletal response at week 2, shocks alone reduced 6% bone mineral content (BMC) in total body (P = 0.06), while shocks with FG-7142 injection reduced not only 11% BMC (P<0.05) but also 6% bone mineral density (BMD) (P<0.05). In addition, FG-7142 injection also caused significant reductions of BMC in specific bones such as femur, lumbar vertebra, and tibia at week 3. Strong negative correlations (R2 = −0.56, P<0.05) and regression (y = 0.2527−0.0037 * x, P<0.01) between freezing behavior and total body BMC in young mice indicated that increased contextual PTSD-like behavior was associated with reduced bone mass acquisition.

Conclusions/Significance

This is the first study to document evidence that traumatic events induce lasting consequences on both behavior and skeletal growth, and electric shocks coupled with injection of anxiogenic FG-7142 in young mice can be used as a model to study the effect of PTSD-like symptoms on bone development.

Background

Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder that occurs following exposure to a traumatic event. However, most individuals do not develop PTSD following even a severe trauma, leading to a search for new variables—such as genetic and other molecular variation— associated with vulnerability and resilience in the face of trauma exposure.

Method

We examined whether serotonin transporter (SLC6A4) promoter genotype and methylation status modified the association between number of traumatic events experienced and PTSD in a subset of 100 individuals from the Detroit Neighborhood Health Study.

Results

Number of traumatic events was strongly associated with risk of PTSD. Neither SLC6A4 genotype or nor methylation status were associated with PTSD in main effects models. However, SLC6A4 methylation levels modified the effect of number of traumatic events on PTSD after controlling for SLC6A4 genotype. Persons with more traumatic events were at increased risk for PTSD but only at lower methylation levels. At higher methylation levels, individuals with more traumatic events were protected from this disorder. This interaction was observed whether the outcome was PTSD diagnosis, symptom severity, or number of symptoms.

Conclusions

Gene-specific methylation patterns may offer potential molecular signatures of increased risk for and resilience to PTSD.

Purpose

Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience.

Methods

We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory).

Results

Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21–0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44–7.01]).

Conclusion

Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a “vaccination” effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations.

Recent work suggests that the 9-repeat (9R) allele located in the 3′UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on population-based samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02–3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a “double hit” model, including both a putatively reduced-function allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus.

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development.

Background

The Great East Japan Earthquake of March 11, 2001 left around 20,000 dead or missing. Previous studies showed that rescue workers, as well as survivors, of disasters are at high risk for posttraumatic stress disorder (PTSD). This study examined the predictive usefulness of the Peritraumatic Distress Inventory (PDI) among rescue workers of Disaster Medical Assistance Teams (DMATs) deployed during the acute disaster phase of the Great East Japan Earthquake.

Methodology/Principal Findings

In this prospective observational study, the DMAT members recruited were assessed 1 month after the earthquake on the PDI and 4 months after the earthquake on the Impact of Event Scale-Revised to determine PTSD symptoms. The predictive value of the PDI at initial assessment for PTSD symptoms at the follow-up assessment was examined by univariate and multiple linear regression analysis. Of the 254 rescue workers who participated in the initial assessment, 173 completed the follow-up assessment. Univariate regression analysis revealed that PDI total score and most individual item scores predicted PTSD symptoms. In particular, high predictive values were seen for peritraumatic emotional distress such as losing control of emotions and being ashamed of emotional reactions. In multiple linear regression analysis, PDI total score was an independent predictor for PTSD symptoms after adjusting for covariates. As for covariates specifically, watching earthquake television news reports for more than 4 hours per day predicted PTSD symptoms.

Conclusions/Significance

The PDI predicted PTSD symptoms in rescue workers after the Great East Japan Earthquake. Peritraumatic emotional distress appears to be an important factor to screen for individuals at risk for developing PTSD among medical rescue workers. In addition, watching television for extended period of time might require attention at a time of crisis.

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs = −0.465; p = 0.011), right (rs = −0.414; p = 0.025), and total hippocampus volume (rs = −0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.

For the first time in human history, more than half of the world's population lives in urban areas and this is projected to increase to two-thirds by 2030. This increased urbanity of the world's population has substantial public health implications. Nearly a century of research has shown higher risk of mental disorder among persons living in urban versus rural areas. Epidemiologic research has documented that associations between particular features of the urban environment, such as concentrated disadvantage, residential segregation and social norms, contribute to the risk of mental illness. We propose that changes in DNA methylation may be one potential mechanism through which features of the urban environment contribute to psychopathology. Recent advances in animal models and human correlation studies suggest DNA methylation as a promising mechanism that can explain how the environment “gets under the skin.” Aberrant DNA methylation signatures characterize mental disorders in community settings. Emerging evidence of associations between exposure to features of the environment and methylation patterns may lead toward the identification of mechanisms that explain the link between urban environments and mental disorders. Importantly, evidence that epigenetic changes are reversible offers new opportunities for ameliorating the impact of adverse urban environments on human health.

Background

Epigenetic markings acquired in early life may have phenotypic consequences later in development through their role in transcriptional regulation with relevance to the developmental origins of diseases including obesity. The goal of this study was to investigate whether DNA methylation levels at birth are associated with body size later in childhood.

Principal Findings

A study design involving two birth cohorts was used to conduct transcription profiling followed by DNA methylation analysis in peripheral blood. Gene expression analysis was undertaken in 24 individuals whose biological samples and clinical data were collected at a mean ± standard deviation (SD) age of 12.35 (0.95) years, the upper and lower tertiles of body mass index (BMI) were compared with a mean (SD) BMI difference of 9.86 (2.37) kg/m2. This generated a panel of differentially expressed genes for DNA methylation analysis which was then undertaken in cord blood DNA in 178 individuals with body composition data prospectively collected at a mean (SD) age of 9.83 (0.23) years. Twenty-nine differentially expressed genes (>1.2-fold and p<10−4) were analysed to determine DNA methylation levels at 1–3 sites per gene. Five genes were unmethylated and DNA methylation in the remaining 24 genes was analysed using linear regression with bootstrapping. Methylation in 9 of the 24 (37.5%) genes studied was associated with at least one index of body composition (BMI, fat mass, lean mass, height) at age 9 years, although only one of these associations remained after correction for multiple testing (ALPL with height, pCorrected = 0.017).

Conclusions

DNA methylation patterns in cord blood show some association with altered gene expression, body size and composition in childhood. The observed relationship is correlative and despite suggestion of a mechanistic epigenetic link between in utero life and later phenotype, further investigation is required to establish causality.

Little is known about the dynamic characteristics of stress system activity during “life as it is lived”. Using as representative a study design as possible, this investigation sought to gain insights into this area. A healthy 25-year-old woman collected her entire urine over a period of 63 days in 12-h intervals (126 measurements) to determine cortisol and neopterin (immune activation marker) levels. In addition, she filled out questionnaires on emotional state and daily routine in 12-h intervals, and was interviewed weekly to identify emotionally negative and positive everyday incidents. Adjusted cross-correlational analyses revealed that stressful incidents were associated with cyclic response patterns in both urinary cortisol and urinary neopterin concentrations. Urinary cortisol levels first decreased 12–24 h after stressful incidents occurred (lag 1: −.178; p = 0.048) and then increased a total of 72–84 h later (lag 6: +.224; p = 0.013). Urinary neopterin levels first increased 0–12 h before the occurrence of stressful incidents (−lag 1: +.185; p = 0.040) and then decreased a total of 48–60 h following such stressors (lag 4: −.181; p = 0.044). Decreases in urinary neopterin levels were also found 24–36 and 48–60 h after increases in pensiveness (lag 2: −.215; p = 0.017) and depressiveness (lag 4: −.221; p = 0.014), respectively. Findings on emotionally positive incidents sharply contrasted with those dealing with negative experiences. Positive incidents were followed first by urinary cortisol concentration increases within 12 h (lag 0: +.290; p = 0.001) and then by decreases after a total of 60–72 h (lag 5: −.186; p = 0.039). Urinary neopterin levels first decreased 12–24 h before positive incidents occurred (−lag 2: −.233; p = 0.010) and then increased a total of 12–24 h following these incidents (lag 1: +.222; p = 0.014). As with previous investigations on patients with systemic lupus erythematosus (SLE), this study showed that stress system response can be considerably longer and more complex and differentiated than findings from conventional group studies have suggested. Further integrative single-case studies will need to be conducted in order to draw firm conclusions about stress system dynamics under real-life conditions.

Objective

To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors.

Design

Cross sectional survey.

Setting

17 general practices in Scotland, United Kingdom.

Participants

Random sampling of over 65 s registered with the practices in four strata young-old (65–80 years), old-old (over 80 years), more affluent and less affluent groups.

Main Outcome Measures

Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling.

Results

547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R2 = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model.

Conclusions

Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.

Background

World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. São Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders.

Methods and Results

A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year.

Discussion

Adults living in São Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.

Background

A history of early adverse experiences is an important risk factor for adult psychopathology. Changes in stress sensitivity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the association between stress and risk for psychiatric disorders. Preclinical work in rodents has linked low levels of maternal care to increased methylation of the promoter region of the glucocorticoid receptor (GR) gene, as well as to exaggerated hormonal and behavioral responses to stress. Recent studies have begun to examine whether early-life stress leads to epigenetic modifications of the GR gene in humans.

Methods

We examined the degree of methylation of a region of the promoter of the human GR gene (NR3C1) in leukocyte DNA from 99 healthy adults. Participants reported on their childhood experiences of parental behavior, parental death or desertion, and childhood maltreatment. On a separate day, participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, a standardized neuroendocrine challenge test.

Results

Disruption or lack of adequate nurturing, as measured by parental loss, childhood maltreatment, and parental care, was associated with increased NR3C1 promoter methylation (p<.05). In addition, NR3C1 promoter methylation was linked to attenuated cortisol responses to the Dex/CRH test (p<.05).

Conclusions

These findings suggest that childhood maltreatment or adversity may lead to epigenetic modifications of the human GR gene. Alterations in methylation of this gene could underlie the associations between childhood adversity, alterations in stress reactivity, and risk for psychopathology.