Monozygotic twins affected with major depressive disorder have greater variance in methylation than their unaffected co-twin

Our understanding of major depressive disorder (MDD) has focused on the influence of genetic variation and environmental risk factors. Growing evidence suggests the additional role of epigenetic mechanisms influencing susceptibility for complex traits. DNA sequence within discordant monozygotic twin (MZT) pairs is virtually identical; thus, they represent a powerful design for studying the contribution of epigenetic factors to disease liability. The aim of this study was to investigate whether specific methylation profiles in white blood cells could contribute to the aetiology of MDD. Participants were drawn from the Queensland Twin Registry and comprised 12 MZT pairs discordant for MDD and 12 MZT pairs concordant for no MDD and low neuroticism. Bisulphite treatment and genome-wide interrogation of differentially methylated CpG sites using the Illumina Human Methylation 450 BeadChip were performed in WBC-derived DNA. No overall difference in mean global methylation between cases and their unaffected co-twins was found; however, the differences in females was significant (P=0.005). The difference in variance across all probes between affected and unaffected twins was highly significant (P<2.2 × 10⁻¹⁶), with 52.4% of probes having higher variance in cases (binomial P-value<2.2 × 10⁻¹⁶). No significant differences in methylation were observed between discordant MZT pairs and their matched concordant MZT (permutation minimum P=0.11) at any individual probe. Larger samples are likely to be needed to identify true associations between methylation differences at specific CpG sites.     

Trends in adolescent alcohol use: effects of age, sex and cohort on prevalence and heritability

Aims To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU). Design Survey study in participants registered with the Netherlands Twin Register. Setting Twins from the general population. Participants Two cohorts (data collected in 1993 and 2005–08) of twins aged 13–15, 16–17 and 18–21 years. In 1993 and 2005–08 a total of 3269 and 8207 twins, respectively, took part. Measurements Survey data on initiation and frequency of alcohol use and quantity of alcohol consumed. Findings The prevalence of alcohol initiation increased between 1993 and 2005–08 for both males and females. The largest difference was for girls observed at ages 13–15, where the prevalence increased from 59.5% to 72.4%. We also found increases in prevalence across cohorts for quantity of alcohol consumed and non‐significant increases for frequency of alcohol use. From age 16 onwards, boys drank more frequently and larger quantities than girls. Genetic model fitting revealed that the genetic architecture of AAU did not differ between birth cohorts, nor were there differences between boys and girls. Genetic factors explained between 21% and 55% of individual differences in alcohol measures throughout adolescence. Shared environment explained between 17% and 64% of variance in alcohol use, across different age groups and alcohol measures. Conclusions In the Netherlands, the prevalence of alcohol initiation, frequency and quantity has increased in adolescents over a 15‐year period, but there are no changes in the genetic architecture of adolescent alcohol use.     

Anesthetic management of premature conjoined twins posted for nonseparation emergency surgery

Craniopagus conjoined twins are rare, and the chance that an anesthesiologist might face the challenge of providing anesthesia for this condition is very rare. The incidence of conjoined twins ranges from 1 : 50 000 to 1 : 200 000 births. We describe the anesthetic management of a pair of premature craniopagus conjoined twins posted for emergency surgery prior to their separation.     

不同绒毛膜性双胎妊娠临床分析

目的 探讨双胎妊娠绒毛膜性对孕期及围生儿预后的影响,进而明确双胎的绒毛膜性诊断、产前管理及双胎特有并发症的处理规范.方法 回顾性分析我院2011-2014年的双胎病例435例,根据绒毛膜性分为单绒毛膜双羊膜囊双胎(monochrionic diamniotic twin,MCDA)和双绒毛膜双羊膜囊双胎(dichorionic diamniotic twin,DCDA)2组,对其孕期并发症、畸形发病率、分娩孕周和新生儿体重及预后等进行分析.结果 MCDA组的自然受孕率和胎儿畸形率(84.38％、7.03％)明显高于DCDA组(38.76％、3.91％,P均＜0.05),差异有统计学意义.MCDA组分娩孕周明显小于DCDA组(33.17±5.25 vs.35.39±3.32,P＜0.001),其急诊剖宫产率明显高于DCDA组[36.19％ (38/105) vs.19.86％ (56/282),P＜0.05],差异均有统计学意义.MCDA组新生儿出生体重明显小于DCDA组,新生儿的轻度、重度窒息率,流产率,胎死宫内发生率均高于DCDA组.生后死亡及死产率发生例数较少,暂无可比性.MCDA组特殊并发症的发生率明显高于DCDA组.结论 双胎妊娠的绒毛膜性判断对于双胎的产前管理及预后可起到关键作用,双胎特殊并发症由于发病机制的不完全明确,其管理及治疗还需要不断总结并个性化指导及治疗.     

Increased methylation at an unexplored glucocorticoid responsive element within exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased hippocampal connectivity

Among the major psychiatric disorders, anxious-depressive disorders stand out as one of the more prevalent and more frequently associated with hypothalamic-pituitary-adrenal (HPA) axis abnormalities. Methylation at the exon 1_F of the glucocorticoid receptor gene NR3C1 has been associated with both early stress exposure and risk for developing a psychiatric disorder; however, other NR3C1 promoter regions have been underexplored. Exon 1_D emerges as a suggestive new target in stress-related disorders epigenetically sensitive to early adversity. After assessment of 48 monozygotic twin pairs (n=96 subjects) informative for lifetime history of anxious-depressive disorders, they were classified as concordant, discordant or healthy in function of whether both, one or neither twin in each pair had a lifetime diagnosis of anxious-depressive disorders. DNA for epigenetic analysis was extracted from peripheral blood. Exon 1_F and exon 1_D CpG-specific methylation was analysed by means of pyrosequencing technology. Functional magnetic resonance imaging was available for 54 subjects (n=27 twin pairs). Exon 1_D CpG-specific methylation within a glucocorticoid responsive element (GRE) was correlated with familial burden of anxious-depressive disorders (r=0.35, z=2.26, p=0.02). Right hippocampal connectivity was significantly associated with CpG-specific GRE methylation (β=?2.33, t=?2.85, p=0.01). Exon 1_F was uniformly hypomethylated across all subgroups of the present sample. GRE hypermethylation at exon 1_D of the NR3C1 gene in monozygotic twins concordant for anxious-depressive disorders suggests this region plays a role in increasing vulnerability to psychosocial stress, partly mediated by altered hippocampal connectivity.     

双胎选择性生长受限危险因素分析及胎盘血管内皮生长因子的表达

目的 研究双胎选择性宫内生长受限（selective intrauterine growth restriction,sIUGR）胎盘血管内皮生长因子（VEGF）的表达并探讨影响妊娠结局的危险因素.方法 2010年6月至2013年6月深圳市人民医院产科分娩双胎妊娠590例,单绒毛膜双羊膜囊（monochorionic diamnotic,MCDA）双胎sIUGR 42例作为病例组,双绒毛膜双胎sIUGR 47例作为对照A组,同期分娩的无sIUGR单绒毛膜双羊膜囊双胎42例作为对照B组.分娩后收集胎盘并分别称重、检测胎盘份额、脐带插入情况.记录新生儿出生体重及围产儿结局.运用免疫组织化学法分别检测病例组和对照组胎盘组织中VEGF的表达,半定量测其表达强度.体重轻者称小胎,体重重者称大胎.结果 病例组、对照A组及对照B组围产儿死亡率分别为17.8％ （15/84）、6.4％（6/94）、1.2％（1/84）,脐带异常插入率分别为48.8％、10.6％、14.3％.病例组大、小胎胎盘重量为（521±149）g vs.（258±53）g.VEGF在病例组、对照A组大婴胎盘组织中的表达强度高于小婴（P＜0.01）.结论 单绒毛膜双羊膜囊双胎sIUGR围产儿死亡率明显升高.双胎sIUGR危险因素主要有胎盘份额分配不均衡、脐带帆状插入、胎盘血管内皮生长因子表达下降等.     

Atrial septal defect in adult identical twins: A variation in theme

The diagnosis of atrial septal defect was established in monozygotic twin females at age 63. Each patient mimicked a different acquired heart disease. One twin had congestive heart failure and atrial fibrillation and was diagnosed as having rheumatic mitral insufficiency. The other twin had atypical chest pain and systemic hypertension and was thought to have arteriosclerotic heart disease. In each case the correct diagnosis was made at cardiac catheterization. Although the same basic congenital heart lesion was present in both patients, the symptoms and findings differed. Symptomatic improvement was achieved by different therapeutic modalities. One patient had open heart surgery, while the other twin improved with medical therapy.     

Associations of sitting time with leisure-time physical inactivity,education, and body mass index change

We aimed to investigate the associations of long-term leisure-time physical inactivity, body mass index (BMI) change, and education with sitting time in a 35-year follow-up based on self-reports in surveys. Influences of working status in 2011 and familial confounding on the associations were tested. Data were based on the population-based Finnish Twin Cohort of 5232 twins (53-67-year-old, 41% men) with four surveys in 1975-2011. Statistical analyses were performed using linear regression with several covariates. The effect of familial confounding (genetics and shared environment) was analyzed using a co-twin control design which should be interpreted as if familial confounding plays a role, an association should be seen among all individuals but not in discordant twin pairs. Compared to those not at work, those at work had a longer total sitting time/d. For those at work, higher education was associated with more total sitting but with less non-work sitting. Long-term leisure-time physical inactivity was associated with more non-work sitting among those at work, whereas long-term weight gain with more total and non-work sitting regardless of working status. Familial confounding attenuated the associations, except for the association of increasing BMI with total and non-work sitting among women at work. To conclude, total sitting time was longer among those still at work, but it was also influenced by long-term leisure-time physical inactivity, higher education, and an increase of BMI over the years. Public health efforts should be targeted to reduce sedentary behavior by promoting life-long leisure-time physical activity and weight control.