The effects of child maltreatment on early signs of antisocial behavior: genetic moderation by tryptophan hydroxylase, serotonin transporter, and monoamine oxidase A genes

Gene-environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes were examined: tryptophan hydroxylase 1 (TPH1), serotonin transporter linked polymorphic region (5-HTTLPR), and monoamine oxidase A (MAOA) upstream variable number tandem repeat. In addition to child maltreatment status, we considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer, and adult counselor reports. In a series of analyses of covariance, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all report forms. Genetic effects operated primarily in the context of gene-environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5-HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer reports of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. The TPH1 and 5-HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult reports of antisocial behavior; again, the genetic effects were strongest for children who were abused. In addition, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult reports of antisocial behavior. The findings elucidate how genetic variation contributes to identifying which maltreated children are most vulnerable to antisocial development.     

Epistatic interaction between the monoamine oxidase A and serotonin transporter genes in anorexia nervosa

The serotonin (5-HT) and norepinephrine (NE) systems are likely involved in the aetiology of anorexia nervosa (AN) as sufferers are premorbidly anxious. Specifically, we hypothesize that genes encoding proteins, which clear 5-HT and NE from the synapse, are prime candidates for affecting susceptibility to AN. Supporting our hypothesis, we earlier showed that the NE transporter (NET) and monoamine oxidase A (MAOA) genes appear to contribute additively to increased risk of developing restricting AN (AN-R). With regard to the MAOA gene, a sequence variant that increases MAOA activity and has suggested association with the anxiety condition, panic disorder was preferentially transmitted from parents to affected children. Here we provide evidence in support of interaction between the MAOA and serotonin transporter (SERT) genes in 114 AN nuclear families (patient with AN plus biological parents). A SERT gene genotype with no apparent individual effect on risk and known to be associated with anxiety is preferentially transmitted to children with AN (chi2 trend=9.457, 1 df, P=0.0021) and AN-R alone (chi2 trend=7.477, 1 df, P=0.0063) when the 'more active' MAOA gene variant is also transmitted. The increased risk of developing the disorder is up to eight times greater than the risk imposed by the MAOA gene variant alone--an example of synergistic epistatic interaction. If independently replicated, our findings to date suggest that we may have identified three genes affecting susceptibility to AN, particularly AN-R: the MAOA, SERT, and NET genes.     

Interactive effects of corticotropin releasing hormone receptor 1, serotonin transporter linked polymorphic region, and child maltreatment on diurnal cortisol regulation and internalizing symptomatology

Within an allostatic load framework, the effect of Gene × Environment (G × E) interactions on diurnal cortisol regulation and internalizing symptomatology were investigated. Variation in the corticotropin releasing hormone receptor 1 (CRHR1) TAT haplotype and serotonin transporter linked polymorphic region (5-HTTLPR) was determined in a sample of maltreated (n = 238, 21.4% with early physical and sexual abuse) and nonmaltreated (n = 255) children (M age = 10.08) participating in a summer research camp. Internalizing and depressive symptoms were assessed by other and self-report. G × E effects for CRHR1 and maltreatment and early abuse on diurnal cortisol regulation were observed; CRHR1 variation was related to cortisol dysregulation only among maltreated children. Early abuse and high internalizing symptoms also interacted to predict atypical diurnal cortisol regulation. The interaction of CRHR1, 5-HTTLPR, and child maltreatment (G × G × E) identified a subgroup of maltreated children with high internalizing symptoms who shared the same combination of the two genes. The findings support an allostatic load perspective on the effects of the chronic stress associated with child maltreatment on cortisol regulation and internalizing symptomatology as moderated by genetic variation.     

Associations among maternal depressive symptomatology,state of mind and parent and child behaviors: Implications for attachment-based interventions

Associations among maternal depressive symptomatology, maternal state of mind with regard to attachment, and mother and child behaviors were examined in the treatment groups of an attachment-oriented intervention for primiparous women at high risk for parenting difficulties. The Adult Attachment Interview (AAI) was completed by 48 intervention and 62 control subjects when their children were 19 months old and the Center for Epidemiologic Studies-Depression Inventory (CES-D) and parent-child laboratory tasks were completed by the same subjects when their children were 24 months old. In the control group, preoccupied tendencies were repeatedly associated with poor outcome; in theintervention group coherence of mind was associated with positive outcome. Maternal depression tended to be associated with hostility in the intervention group. Results suggest that maternal state of mind may exert powerful effects on parenting behavior and that an attachmentoriented intervention may influence these associations, particularly among preoccupied subjects. Results also demonstrated potential benefits of using AAI scales in addition to the traditional categories.     

Sociodemographic,sexual, and reproductive variables associated with pregnancy among adolescents from low socioeconomic background

Adolescent pregnancy remains a public health concern in both developed and developing countries. Portugal and Brazil represent some of the best examples of this phenomenon. The present study aimed to identify sociodemographic, sexual, and reproductive health-related variables associated with adolescent pregnancy among students from low socioeconomic backgrounds in both countries. The sample included 984 female adolescents, among whom 215 became pregnant. Living with a partner and lack of information about sex and contraception from the family were the best explicative factors for pregnancy occurrence in both countries. Country-specific variables were also identified. Our results may contribute to developing global preventive interventions, addressing the school as an ideal setting for primary intervention and considering culture-specific characteristics of high-risk populations.     

强迫症与5-羟色胺转运体基因多态性遗传关联病例对照研究的meta分析

目的:用对病例对照研究的数据作meta分析的方法,综合评价强迫症与5-羟色胺(5-HT)转运体基因的启动子区域(5-HTTLPR)和第二内含子多态性(5-HTTVNTR)的关系,为强迫症的遗传背景提供进一步证据。方法:检索MEDLINE、EMBASE、PubMed、CNKI、万方等数据库,收集强迫症与5-HTTLPR基因多态性及5-HTTVNTR基因多态性相关性的病例对照研究,并以OR值为效应指标,基因型在对照群体中的分布均符合Hardy-Weinberg遗传平衡定律,应用CMA2.0软件对各项数据进行统计分析。结果:符合纳入标准的有23篇文献。结果显示,就强迫症与5-HTTLPR多态性相关性而言,亚洲人群中,L等位基因较S等位基因(OR=1.27,95%CI=1.05～1.52)、LL基因型较LS+SS基因型(OR=1.78,95%CI=1.15～2.74)在强迫症患者中的分布频率高于对照组;高加索人群中,SS基因型较LS+LL基因型在强迫症患者中的分布频率高于对照组(OR=1.21,95%CI 1.02～1.44)。就强迫症与5-HTTVNTR多态性相关性而言,高加索人群中10/10基因型较10/12+12/12基因型(OR=0.41,95%CI=0.24～0.71)在强迫症患者中的分布频率低于对照组。结论:现有研究证据提示强迫症与5-HTT基因存在关联,并且在不同种族存在差异。在亚洲人群中5-HTTLPR多态性的L等位基因以及基因型LL可能是强迫症的危险因素,SS基因型是保护因素;在高加索人群中5-HTTLPR多态性的SS基因型则可能是危险因素,5-HTTVNTR基因多态性的10/10基因型是保护因素。     

Family, peer, and individual correlates of depressive symptomatology among U.S. and Chinese adolescents

This study examined the correlates of symptoms of depressed mood among adolescents in 2 dramatically different cultures (n = 502 in Tianjin, People's Republic of China; n = 201 in greater Los Angeles). Gender, stressful life events, perceived parental warmth, and conflict with parents were associated in the expected direction with depressive symptoms in each cultural setting. As predicted, regression analyses showed that the quality of family relationships and grades in school had significantly stronger associations with depressive symptoms among Chinese youths than among U.S. youths, whereas gender differences in depressive symptoms were greater among the U.S. youths. Peer warmth moderated the effects of particular risk factors for depressive symptoms in each cultural setting.     

Association between major depressive disorder and the norepinephrine transporter polymorphisms T-182C and G1287A: A meta-analysis

Background

Previous studies have implicated norepinephrine transporter (NET) gene polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide NET polymorphisms, T-182C (rs2242446) in the promoter region and G1287A (rs5569) in exon 9, were found to be associated with MDD in different populations. However, inconsistent and inconclusive results have also been obtained.

Methods

In this study, we examined whether rs2242446 and rs5569 genetic variants are related to the etiology of MDD using a meta-analysis. Relevant case-control studies were retrieved by database searching and selected according to established inclusion criteria.

Results

Eight articles were identified that tested the relationship between the NET T-182C and/or G1287A polymorphism and MDD. Statistical analyses revealed no significant association between these polymorphisms and MDD (OR=1.23, 95% CI=0.77−1.97, P=0.38 for T-182C; OR=1.00, 95% CI=0.78−1.29, P=0.99 for G1287A).

Limitations

The results must be treated with caution because of the small sample sizes of several included studies.

Conclusions

Our findings suggest that the NET T-182C and G1287A polymorphisms are not susceptibility factors for MDD.     

The association of low socioeconomic status and the risk of having a child with Down syndrome: a report from the National Down Syndrome Project

PurposeAdvanced maternal age and altered recombination are known risk factors for Down syndrome cases due to maternal nondisjunction of chromosome 21, whereas the impact of other environmental and genetic factors is unclear. The aim of this study was to investigate an association between low maternal socioeconomic status and chromosome 21 nondisjunction.MethodsData from 714 case and 977 control families were used to assess chromosome 21 meiosis I and meiosis II nondisjunction errors in the presence of three low socioeconomic status factors: (i) both parents had not completed high school, (ii) both maternal grandparents had not completed high school, and (iii) an annual household income of <$25,000. We applied logistic regression models and adjusted for covariates, including maternal age and race/ethnicity.ResultsAs compared with mothers of controls (n = 977), mothers with meiosis II chromosome 21 nondisjunction (n = 182) were more likely to have a history of one low socioeconomic status factor (odds ratio = 1.81; 95% confidence interval = 1.07–3.05) and ≥2 low socioeconomic status factors (odds ratio = 2.17; 95% confidence interval = 1.02–4.63). This association was driven primarily by having a low household income (odds ratio = 1.79; 95% confidence interval = 1.14–2.73). The same statistically significant association was not detected among maternal meiosis I errors (odds ratio = 1.31; 95% confidence interval = 0.81–2.10), in spite of having a larger sample size (n = 532).ConclusionWe detected a significant association between low maternal socioeconomic status and meiosis II chromosome 21 nondisjunction. Further studies are warranted to explore which aspects of low maternal socioeconomic status, such as environmental exposures or poor nutrition, may account for these results.Genet Med15 9, 698–705.     

Contingent engagement: What we learn from patients with complex health problems and low socioeconomic status

Objective

Elicit patients’ perceptions of factors that facilitate their engagement in care

Recovery from major depressive disorder among female adolescents: a prospective test of the scar hypothesis

This study examined the psychosocial consequences of experiencing major depressive disorder (MDD). In a 7-year longitudinal study of 496 female adolescents, the authors identified 49 girls who experienced their first episode of MDD and then recovered. They were compared with a randomly selected group of 98 never depressed participants on 13 psychological, social, psychiatric, and life events variables. None of the variables fit the scar pattern (i.e., a group difference that emerges during the first MDD episode and remains elevated post-recovery). All 13 variables were elevated before, during, and after the MDD episode, although some increased during the MDD episode. Results provide little support for the scar hypothesis among adolescent girls but instead suggest that many risk variables are elevated before and after the MDD episode. Interventions that modify these factors may help to reduce depression incidence and recurrence among female adolescents.     

The relation between subjective well-being and career aspirations amongst a sample of adolescents in low socioeconomic status communities in Cape Town

The study aimed to determine the relation between adolescents’ subjective well-being and career aspirations. The study further aimed to determine the extent to which social support mediates this relation. The sample comprised 1082 adolescents in Grades 8–11, selected from schools located in low socioeconomic status communities in Cape Town, South Africa. The overall model demonstrated a nonsignificant relation between adolescents’ subjective well-being and career aspirations. Across gender, the results indicated a significant relation between subjective well-being and career aspirations for the male group, but not for females. The results further indicate that social support did not mediate the relation between adolescents’ subjective well-being and career aspirations for the pooled sample. However, for females, the study found a significant negative relation between social support and aspirations. We recommend targeting interventions at an institutional level, inclusive of challenging gender roles and providing information about educational and career opportunities for young people.     

Differences in development and the prevalence of obesity among children and adolescents in different socioeconomic status districts in Shandong,China

Background: There are wide-ranging differences in human growth, not only between ethnic groups but also between regions. Shandong is one of the most populous provinces in China, with inequalities of regional economic status. However, no studies on the differences in development among children and adolescents in different districts have been reported.

Aim: This study assessed the differences in height, weight and prevalence of obesity among children and adolescents of different socioeconomic status (SES) districts in Shandong, China.

Subjects and methods: Data for this study were obtained from a large cross-sectional survey of schoolchildren. A total of 42 286 students (21 222 boys and 21 064 girls) aged 7–18 years from 16 districts participated in this study. Height and weight of all subjects were measured and BMI was calculated from their height and weight. Prevalence rates of obesity and overweight were determined by comparing calculated BMIs (kg/m²) to International Obesity Task Force (IOTF) cut-offs. Each of the 16 districts was assigned an SES ranking (low, moderate, high) based on per capita GDP and income in urban and rural areas. Comparisons of height, weight and the prevalence of overweight and obesity among different groups were made.

Results: Significant differences between SES groups were observed for height, weight and the prevalence of overweight and obesity. Boys and girls from high SES group were taller, heavier and more likely to be obese than their peers from moderate and low SES groups. The prevalences of combined overweight and obesity in the three SES groups were 18.46%, 21.08% and 27.31% in boys and 10.43%, 12.42% and 15.18% in girls, respectively.

Conclusion: There have been obvious regional variations in development and the prevalence of obesity in children and adolescents in Shandong, China, These variations in development and prevalence of obesity in children and adolescents among different SES districts being related to the local SES, process of urbanization, living environments, nutritional status, dietary pattern, physical activity and public health.     

Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence

The impact of socioeconomic status (SES) and genetic polymorphisms on individual differences for externalized behaviors have often been investigated separately in studies of children and adults. In a general population sample of 607 Italian preadolescents, we examined the independent and joint effects of SES and the dopamine receptor D4 (DRD4) and serotonin transporter linked promoter region (5-HTTLPR) polymorphisms upon rule-breaking and aggressive behaviors measured with the Child Behavior CheckList/6-18. We found evidence, which was based on both one locus and two-loci genotype analyses, that low SES and DRD4 long and 5-HTTLPR long alleles, both alone and in interaction, are associated with higher aggressive behavior scores. The effects were similar but more modest and limited to one locus genotype analyses for rule-breaking behavior. Consistent with studies that showed the effects of societal moderators on the heritability of externalized behaviors across different segments of the population, we suggest that diminished social constraints associated with low parental SES may act as enhancers of the genetic influence of specific DRD4 and 5-HTTLPR alleles over aggressive behaviors in preadolescence.