Discordant Twins Research Articles

Is Cancer Associated With Frailty? Results From a Longitudinal Study of Old Danish Twins.

Although age is an important risk factor for both cancer and frailty, it is unclear whether cancer itself increases the risk of frailty. We aimed to assess the association between cancer and frailty in a longitudinal cohort of older Danish twins, taking familial effect into account. Using the Danish Cancer Registry, cancer cases were identified among participants aged 70 and over in the Longitudinal Study of Aging Danish Twins (LSADT). Frailty was evaluated over 10 years of follow-up using the frailty index (FI) and defined as FI > 0.21. Stratified Cox regressions were performed on discordant twin pairs (pairs where one twin had incident cancer and the other was cancer-free) and on all LSADT individual twins (twin pairs and singletons) with no history of cancer. Among the 72 discordant pairs (n = 144, median age at inclusion = 75) included in the study, the median FI at inclusion was 0.08 for both cancer twins and cancer-free co-twins. From the stratified Cox regression, twins with cancer had an increased hazard of developing frailty (hazard ratio [HR] = 3.67, 95% confidence interval [CI] = 1.02-13.14) compared with their cancer-free co-twins. The analyses on individual twins (n = 4 027) provided similar results, showing an increased hazard of frailty in individuals with cancer (HR = 2.57, 95% CI = 1.77-3.74) compared with those without cancer. We showed a higher risk of becoming frail following a cancer diagnosis in both discordant twin pairs and individual twins. These findings support the importance of monitoring frailty in older adults with cancer through geriatric assessments and the implementation of frailty interventions.

Two identical twin pairs discordant for longstanding anorexia nervosa and OSFED: lived experience accounts of eating disorder and recovery processes

Research into the risk of anorexia nervosa (AN) has examined twin pairs to further the understanding of the contributions of genetics, trait inheritance, and environmental factors to eating disorder (ED) development. Investigations of twin experiences of EDs have been biologically-based and have not considered the qualitative, phenomenological aspects of twin experiences. A gap in the literature exists regarding understanding of discordant twins with EDs. This research was developed in response, with the aim to deepen understanding of AN in discordant twins and to create novel ideas for further research and testing. The case studies presented in this article provide lived experience insights of two identical discordant twin pairs: one twin pair discordant for longstanding AN and one twin pair discordant for ‘atypical’ AN (the twin with AN has recovered). The perspectives and experiences of each co-twin (one with AN and one without) explore a number of factors that may have contributed to twin discordance in these cases, and how each twin has responded to the impact of AN in their lives. Through use of first-person accounts in case study presentation, this article centres social justice values of lived experience leadership and involvement in research. This article aims to extend current knowledge and understanding of EDs in discordant twins, particularly regarding risk for ED development, ED duration, diagnosis and treatment, and recovery processes.

Migraine heritability and beyond: A scoping review of twin studies.

This scoping review aimed to summarize current knowledge from twin studies on migraine. Migraine heritability, genetic correlations with migraine comorbid disorders, and the use of discordant twin pairs in migraine research are described. Further, the review considers the unused potential of twin studies in migraine research and reflects on future directions. Twin studies can be used to understand how heritable and environmental factors influence human traits and disorders. The classical twin design compares the resemblance of a trait in monozygotic twins to that in dizygotic twins. The classical twin design can be extended to estimate the genetic correlation between disorders, model causality, and describe differences within discordant twin pairs. Studies focusing on migraine and using a twin study design were included. The search was performed on the PubMed-MEDLINE database using the search terms "migraine" AND "twin" OR "twins." It was done in May 2023, rerun in November 2023, and managed with the Covidence software. The search identified 52 twin studies on migraine. In 24 papers, the heritability of migraine was estimated with a classical twin design. Heritability estimates ranged from 0.36 to 0.48 for studies with adults, both men and women, and unspecified migraine. Migraine heritability was predominantly estimated with twin cohorts of North European ancestry, and only two studies examined migraine subtypes. A multilevel classical twin design was used in 11 studies to examine the co-occurrence between migraine and comorbid disorders. The differences within migraine discordant twin pairs were examined in nine studies. The heritability of migraine was estimated with a classical twin design in twin cohorts from seven different countries, with remarkably similar results across studies. Future studies should include migraine subtypes and twin cohorts of non-North European ancestry to better reflect the global population. Beyond heritability estimations, the twin method is a valuable tool for understanding causality and describing differences within discordant twin pairs. Despite more than 80 years of twin studies in migraine research, the twin design has a large unused potential to advance our understanding of migraine.

Does Catch-Up Growth Come with a Cognitive Cost? Cognitive Outcome and Growth Patterns in Growth Discordant Identical Twins

To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2years was calculated as (weight [kg] at 2years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with β-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P<.0001). Adjusted for birth weight z score and gestational age, CUG in the first 2years after birth was not significantly associated with FSIQ (β-coefficient 0.108 [95% CI -1.373 to 1.590], P=.886). Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.

Monozygotic twins discordant for depression: An extended network comparison of depressive symptoms, cognitive functions and daily activities

Monozygotic twins share the same genotype; however, they can be phenotypically discordant on various traits. Studying discordant monozygotic twins allows the investigation of differences in associations between symptoms and psychopathological risk factors, controlled for shared genetic liability. The network approach to psychopathology suggests that depressive symptoms, along with risk and protective factors (e.g., cognition, daily activities), form a complex system of mutually interacting components. We compared monozygotic twins discordant for lifetime depression on their respective extended networks of depressive symptoms, cognitive functions and daily activities (intellectual, physical, social), and evaluated if these networks differ in their associations between variables and in the role of each variable within the network. Regularized partial correlations investigated the networks' composition in 147 monozygotic twin pairs discordant for depression from the Danish Twin Registry. Affected twins had stronger overall associations within their network of depressive symptoms, cognitive functions and daily activities than their unaffected co-twins, while the importance of the network components’ associations did not differ between the co-twins. In affected twins, decreased frequency in experiencing happiness had the strongest association with remaining variables (i.e., the most influence in activating other network elements). Also, variables from different groups were significantly associated (e.g., loneliness with delayed memory, pessimism with low social activities, verbal learning with intellectual activities). In unaffected twins, both mood symptoms and cognitive functions were important, but between-groups associations were quasi-absent. These results suggest that external events affecting the ability to feel happiness likely trigger the psychopathological process (depression network activation), independently from the genetic predisposition to depression.

Association between first-trimester uterine artery Doppler and crown-rump length with growth discordance: does it make a difference.

The purpose of this study was to investigate the association between first-trimester uterine artery pulsatility index (UtA-PI) and crown-rump length discordance (CRLD) with growth discordance (GD) in twins and analyze the influence of chorionicity in these parameters. This retrospective analysis integrated data from the twin pregnancy database of Centro Hospitalar São João (2019-2023), including 184 fetuses, with 19 monochorionic and 73 dichorionic gestations. To determine the association between UtA-PI and CRLD with GD, correlation analyses were computed and linear regression models were carried out. Separate analyses were conducted for each type of placentation. Logistic regression analysis was carried out to determine the association of mean UtA-PI and CRLD with severe GD, defined as discordance≥25 %. GD≥25 % was detected in 9.80 % of pregnancies. A statistically significant difference between monochorionic and dichorionic gestations was found in crown-rump length (p=0.009), CRLD (p<0.001) and birth weight (p=0.025), but not in mean UtA-PI (p=0.853) or GD (p=0.556). Mean UtA-PI was significantly higher in discordant than in concordant pairs (p<0.001), but that association was not seen in CRLD (p=0.931). Mean UtA-PI and GD were correlated by the regression line "GD=3.844×UtA-PI+6.638", with R2 0.027. CRLD and GD were correlated by the regression line "GD=0.280×CRLD+10.79", with R2 0.010. Mean UtA-PI, but not CRLD, was significantly associated with severe GD (odds ratio, 22.753; p=0.002). Mean UtA-PI, but not CRLD, is associated with GD. The prevalence of severe GD increases significantly with increasing mean UtA-PI.

Williams-Campbell syndrome case series and discordant twins.

Williams-Campbell syndrome (WCS) presents diagnostic challenges. This case series highlights clinical complexities and genetic/environmental interplay, and underscores the need for personalised treatment approaches. #WCS #RareDisease https://bit.ly/3Xqze8x.

Adolescent leisure-time physical activity and eating disorders: a longitudinal population-based twin study

PurposeHigh levels of physical activity have been documented in eating disorder patients. Our aim was to examine whether adolescent leisure-time physical activity is prospectively associated with eating disorders in adolescence and young adulthood.MethodsFinnish twins born in 1983–1987 reported their physical activity frequency at ages 12, 14, and 17. A subsample of participants underwent structured, retrospective interviews for eating disorders at the mean age of 22.4 years. Associations between female twins’ physical activity and future eating disorders (571–683 twins/wave) were investigated with the Cox proportional hazards model. To illustrate the physical activity similarity of the co-twins in a twin pair, we used cross-tabulation of eating disorder–discordant twin pairs (13–24 pairs/wave).ResultsAfter adjusting for several covariates, we found no statistically significant longitudinal association between physical activity and eating disorders. This applied when all eating disorders were combined but also when assessed separately as restrictive and non-restrictive eating disorders. Co-twins’ physical activity in adolescence tended to be similar irrespective of their future eating disorder, supporting the results of the regression analysis.ConclusionWe observed no evidence of adolescent physical activity frequency being prospectively associated with eating disorders in female twins. Further longitudinal studies with larger sample sizes and more detailed physical activity data are needed.Level of evidence: III, evidence obtained from cohort or case–control analytic studies.

An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients

Background/ObjectiveLow birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS). Methods46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire. ResultsFrom the parents’ perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, β=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, β=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, β=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin −1.18, larger twin −0.08, p<0.001) to present (mean SDS: smaller twin −1.16, larger twin −0.14, p<0.001). ConclusionHigher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents’ perspective on the smaller twins’ behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

APOE Genotype, ApoE Plasma Levels, Lipid Metabolism, and Cognition in Monozygotic Twins with, at Risk of, and without Affective Disorders.

Background: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel therapeutic approaches. Methods: We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR). Results: The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L, p = 0.037). Limitations: The present study could benefit from a larger sample size. We did not assess dietary habits. Conclusions: The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.

Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study

Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Ultrasound Differentiation of Twins with Discordant Congenital Diaphragmatic Hernia in the Delivery Room

AbstractMost infants with prenatally diagnosed congenital diaphragmatic hernia (CDH) are intubated rapidly after birth to optimize oxygenation and ventilation while avoiding abdominal distention and high mean airway pressures. A twin pregnancy complicated by one twin with a CDH diagnosis is a rare event and is associated with preterm delivery and low birth weight compared to singletons with CDH. In rare cases of discordant CDH in twin pregnancies with an absence of external distinguishing features (similar weights, fetal presentation, and sex), it may be difficult to quickly determine which twin has CDH in the delivery room (DR), raising ambiguity about the best management of both infants. This case describes the successful use of ultrasound (US) in the DR to rapidly diagnose the presence or absence of CDH in discordant twins. By developing a resuscitation algorithm and using in situ simulations prior to delivery, the twin with CDH was rapidly identified, intubated, and transported to the neonatal intensive care unit (NICU) for further management. The twin without CDH received routine care and was transferred to the well-baby nursery. Interprofessional planning and simulation may be used to design a safe resuscitation plan incorporating US diagnosis of diaphragmatic anomalies into the Neonatal Resuscitation Program (NRP) algorithm.

Abstract P221: Association of Posttraumatic Stress Disorder With Physical Activity Among Vietnam-Era Male Twin Veterans

Introduction: Post-traumatic stress disorder (PTSD) can develop after a traumatic event and is associated with cardiovascular diseases (CVDs), but the mechanisms are not clear. Behavioral factors like physical activity (PA) may play a role if associated with PTSD, but few studies have examined whether PTSD may be associated with lower PA. By studying twins, we can examine this relationship and adjust for demographic and shared familial characteristics. Methods: We studied the relationship between current PTSD diagnosis and PA in 146 male twins (73 pairs) from the Emory Twin Study within the Vietnam Twin Registry. Twin pairs were discordant for PTSD symptoms. PA was continuously measured over 7 days using wrist actigraphy and used validated algorithms to calculate daily hours of sedentary time and moderate-to-vigorous PA (MVPA). We also examined self-reported leisure PA score with the Baecke questionnaire. We controlled for familial effect using generalized linear regression within PTSD discordant twin pairs. We dichotomized MVPA based on established cutpoints for normal values and estimated the prevalence ratio (PR) of the likelihood of achieving the minimum recommended average daily MVPA using Poisson regression. Multiple imputation was used to reduce the impact of missing data. Results: Veterans (mean (SD) age: 68.2 (2.1); 97% (142/146) White) had a low prevalence of achieving daily MVPA goals —35% among those with PTSD and 25% among those without and spent over 9 average sedentary hours per day. We did not find any significant relationship between current PTSD diagnosis and any of the PA outcomes in fully adjusted models. Discussion: Our findings reveal low PA and high levels of sedentary behavior among Veterans, with PTSD showing no significant impact on average PA. This suggests that PA is unlikely to explain excess CVD risks that have otherwise been observed in PTSD. Nonetheless, in this cohort of Vietnam era veterans, interventions to increase PA are warranted regardless of PTSD status.

Can flow proneness be protective against mental and cardiovascular health problems? A genetically informed prospective cohort study

Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.

Adverse Childhood Experiences and Adult Mental Health Outcomes

Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

Birth weight discordance and adverse neonatal outcomes in appropriately grown premature twins

ObjectiveThis study aimed to analyze the clinical characteristics of birth weight discordant twins (BWDT) who were premature and appropriate-for-gestational-age or large-for-gestational-age. Additionally, it assessed the impact of birth weight discordance on the prognosis of appropriately grown premature twins, and investigated the effect of maternal factors on neonatal outcomes. Study designThis retrospective cohort study included twins who were born alive after preterm labor at the Nanjing Drum Tower Hospital from January 2018 to December 2021, along with their mothers. Twins were arranged into discordant and concordant groups according to intertwin birth weight discordance, followed by the analysis of the clinical characteristics of mothers and the prognosis of neonates. ResultsA total of 585 mothers and 1170 neonates were included, with 47 mothers and 94 neonates in the discordant group. The incidence of birth weight discordance was 8.0% (94/1,170) in appropriately grown premature twins. The incidence of complications (43.2% vs. 21.8%) and transfer to the neonatal intensive care unit (NICU) (53.2% vs. 29.2%) was higher in the discordant group than in the concordant group (p < 0.05). Furthermore, the incidence of infectious diseases (36.7% vs. 19.4%), necrotizing enterocolitis (7.6% vs. 1.6%), and oxygen therapy rate (22.8% vs. 12.8%) were statistically significantly higher in the discordant group than in the concordant group (p < 0.05). ConclusionBirth weight discordance remains a high-risk factor for complications and transfer to the NICU in appropriately grown premature twins. It is important to pay attention to birth weight discordance when the outcomes of twins are assessed.

A Mass Spectrometry-Based Proteome Study of Twin Pairs Discordant for Incident Acute Myocardial Infarction within Three Years after Blood Sampling Suggests Novel Biomarkers.

Acute myocardial infarction (AMI) is a major cause of mortality and morbidity worldwide, yet biomarkers for AMI in the short- or medium-term are lacking. We apply the discordant twin pair design, reducing genetic and environmental confounding, by linking nationwide registry data on AMI diagnoses to a survey of 12,349 twins, thereby identifying 39 twin pairs (48-79 years) discordant for their first-ever AMI within three years after blood sampling. Mass spectrometry of blood plasma identified 715 proteins. Among 363 proteins with a call rate > 50%, imputation and stratified Cox regression analysis revealed seven significant proteins (FDR < 0.05): FGD6, MCAM, and PIK3CB reflected an increased level in AMI twins relative to their non-AMI co-twins (HR > 1), while LBP, IGHV3-15, C1RL, and APOC4 reflected a decreased level in AMI twins relative to their non-AMI co-twins (HR < 1). Additional 50 proteins were nominally significant (p < 0.05), and bioinformatics analyses of all 57 proteins revealed biology within hemostasis, coagulation cascades, the immune system, and the extracellular matrix. A protein-protein-interaction network revealed Fibronectin 1 as a central hub. Finally, technical validation confirmed MCAM, LBP, C1RL, and APOC3. We put forward novel biomarkers for incident AMI, a part of the proteome field where markers are surprisingly rare and where additional studies are highly needed.