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Emotional complexity (EC) involves the ability to distinguish between distinct emotions (differentiation) and the experience of a large range of emotions (diversity). Lower EC has been related to psychopathology in cross-sectional studies. This study aimed to investigate (a) whether EC prospectively predicts psychopathology and (b) whether this effect is contingent on stressful life events. To further explore EC, we compared the effects of differentiation and diversity. Adolescents from the general population (N = 401) rated 8 negatively valenced emotions 10 times a day for 6 consecutive days. Further, they completed the Symptom Checklist-90 (baseline and 1-year follow-up) and a questionnaire on past year's life events at follow-up. Logistic regression analyses tested whether EC-reflected by emotion differentiation (intraclass correlation coefficient [ICC]) and diversity (diversity index [DI])-predicted prognosis (good: remitting or lacking symptoms vs. bad: worsening or persisting symptoms). EC predicted prognoses but only when based on the ICC (OREC.ICC = 1.42, p = .02). An ECICC 1 SD above average increased the probability of good prognosis from .67 to .74. This effect was not related to stressful life events (OREC × Life events = 1.03, p = .86) and disappeared when emotion intensity (mean level) was taken into account (OREC = 1.20, p = .20). Predicting future prognosis does not necessitate complex measures of emotional experience (ICC, DI) but rather might be achieved through simpler indices (mean). The discrepant effects of the ICC and DI on prognosis suggest that impaired emotion representation (ICC) plays a more important role in vulnerability to mental ill health than does low diversity of emotions (DI). (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Parents are known to provide a lasting basis for their children's social development. Understanding parent-driven socialization is particularly relevant in adolescence, as an increasing social independence is developed. However, the relationship between key parenting styles of care and control and the microlevel expression of daily-life social interactions has been insufficiently studied. Adolescent and young adult twins and their nontwin siblings (N = 635; mean age = 16.6; age range = 14.2-21.9; 58.6% female; 79.5% in or having completed higher secondary/tertiary education; 2.8% speaking language other than Dutch at home) completed the Parental Bonding Instrument (PBI) on parental care and control. Participants also completed a 6-day experience sampling period (10 daily beeps, mean compliance = 68.0%) to assess daily-life social interactions. Higher overall parental bonding quality (of both parents) related to more positive social experiences in daily life (e.g., belonging in company), but not to more social behaviors (e.g., being with others). Factor analysis indicated a three-factor structure of the PBI, with care, denial of psychological autonomy, and encouragement of behavioral freedom. Paternal care was uniquely predictive of better social experiences. These findings demonstrate how parenting styles may be uniquely associated with how adolescents experience their social world, with a potentially important role for fathers in particular. This complements the long-held idea of socialization through parenting by bringing it into the context of daily life and implies how both conceptualizations of social functioning and interventions aimed at alleviating social dysfunction might benefit from a stronger consideration of day-to-day social experiences. (PsycInfo Database Record (c) 2022 APA, all rights reserved). ispartof: DEVELOPMENTAL PSYCHOLOGY vol:58 issue:4 pages:792-805 ispartof: location:United States status: published

Studies based on self-reported alcohol consumption and telomere length show inconsistent results. Therefore, we studied the association between gamma-glutamyl transferase (GGT), a widely used biomarker of alcohol intake, and telomere length. The possible health relevance in young adulthood was explored by investigating cardiometabolic risk factors. Mixed modelling was performed to examine GGT and alcohol consumption in association with telomere length in buccal cells of 211 adults between 18 and 30 years old of the East Flanders Prospective Twin Survey. In addition, we investigated the association between GGT and cardiometabolic risk factors; waist circumference, systolic blood pressure, fasting glucose, HDL cholesterol, and triglycerides. Although we did not observe an association between self-reported alcohol consumption and telomere length, our results show that a doubling in serum GGT is associated with 7.80% (95% CI - 13.9 to - 1.2%; p=0.02) shorter buccal telomeres, independently from sex, chronological age, educational level, zygosity and chorionicity, waist-to-hip ratio and smoking. The association between GGT was significant for all five cardiometabolic risk factors, while adjusting for age. We show that GGT, a widely used biomarker of alcohol consumption, is associated with telomere length and with risk factors of cardiometabolic syndrome, despite the young age of this study population. This investigation is supported by the EU research council “project ENVIRONAGE” (ERC-2012-StG 310890), and the Flemish Scientifc Fund (FWO, G073315N). Dr. Bijnens holds a fellow-ship from the Marguerite-Marie Delacroix foundation. Dr. Martens is a postdoctoral fellow of the FWO (12X9620N). Since its start, the East Flanders Prospective Twin Survey has been partly supported by grants from the Fund of Scientifc Research Flanders and Twins, a non-proft Association for Scientifc Research in Multiple Births (Belgium).

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness. ispartof: ACTA PSYCHIATRICA SCANDINAVICA vol:141 issue:5 pages:465-475 ispartof: location:United States status: published

Environmental and individual contextual factors profoundly influence how people regulate their emotions. The current article addresses the role of event intensity and psychopathology (an admixture of depression, anxiety, and psychoticism) on emotion regulation in response to naturally occurring events. For six days each evening, a youth sample (aged 15–25, N = 713) recorded the intensity of the most positive and most negative event of the day and their subsequent emotion regulation. The intensity of negative events was positively associated with summed total emotion regulation effort, strategy diversity, engaging in rumination, situation modification, emotion expression, and sharing and negatively associated with reappraisal and acceptance. The intensity of positive events was positively associated with strategy diversity, savoring, emotion expression, and sharing. Higher psychopathology symptoms were only related to ruminating more about negative events. We interpret these findings as support for the role of context in the degree of effort and type of emotion regulation that young people engage in.

Background Recent theories argue that an interplay between (i.e., network of) experiences, thoughts and affect in daily life may underlie the development of psychopathology. Objective To prospectively examine whether network dynamics of everyday affect states are associated with a future course of psychopathology in adolescents at an increased risk of mental disorders. Methods 159 adolescents from the East-Flanders Prospective Twin Study cohort participated in the study. At baseline, their momentary affect states were assessed using the Experience Sampling Method (ESM). The course of psychopathology was operationalized as the change in the Symptom Checklist-90 sum score after 1 year. Two groups were defined: one with a stable level (n = 81) and one with an increasing level (n = 78) of SCL-symptom severity. Group-level network dynamics of momentary positive and negative affect states were compared between groups. Results The group with increasing symptoms showed a stronger connections between negative affect states and their higher influence on positive states, as well as higher proneness to form ‘vicious cycles’, compared to the stable group. Based on permutation tests, these differences were not statistically significant. Conclusion Although not statistically significant, some qualitative differences were observed between the networks of the two groups. More studies are needed to determine the value of momentary affect networks for predicting the course of psychopathology.

Background: Telomere length (TL) is considered a biological marker of aging and may indicate age-related disease susceptibility. Adults and children show a fixed ranking and tracking of TL over time. However, the contribution of an individual's initial birth TL to their later life TL is unknown. We evaluated change and tracking of TL from birth to child-and adulthood. Methods: Telomere length at birth was measured using qPCR in two independent prospective birth cohorts. After a median follow-up period of 4 years in ENVIRONAGE (n = 273) we assessed leukocyte telomere length (LTL) and after 23 years in EFPTS (n = 164) buccal TL was assessed. Correlations and multivariable regression models were applied to study telomere tracking and determinants of TL change from birth onwards. Findings: In children, LTL at the age of 4 correlates with TL at the start of life both in cord blood (r = 0.71, P < 0.0001;) and placenta (r = 0.60, P < 0.0001) and was À11.2% and À33.1% shorter, respectively. In adult-hood, buccal TL at the age of 23 correlates with placental TL (r = 0.46, P < 0.0001) and was À35.9% shorter. TL attrition was higher in individuals with longer birth TL. However, based on TL ranking, individuals do not tend to change dramatically from TL rank after 4 or 23 years of follow-up. Finally, longer maternal TL associates with lower telomere attrition in the next generation. Interpretation: The high prediction of newborn TL for later life TL, and stable TL ranking from birth onwards underscores the importance of understanding the initial setting of newborn TL and its significance for later life. This research was funded by European Research Council (ERC-StG310898) and the Flemish Scientific Fund (FWO). Dries Martensholds a postdoctoral grant by the Flemish Scientific Fund (FWO grant12X9620N). The researchers would like to thank all the ENVIRONAGEfollow-up study researchers.

Background Despite the increasing understanding of factors that might underlie psychiatric disorders, prospectively detecting shifts from a healthy towards a symptomatic state has remained unattainable. A complex systems perspective on psychopathology implies that such symptom shifts may be foreseen by generic indicators of instability, or early warning signals (EWS). EWS include, for instance, increasing variability, covariance, and autocorrelation in momentary affective states—of which the latter was studied. The present study investigated if EWS predict (i) future worsening of symptoms as well as (ii) the type of symptoms that will develop, meaning that the association between EWS and future symptom shifts would be most pronounced for congruent affective states and psychopathological domains (e.g., feeling down and depression). Methods A registered general population cohort of adolescents (mean age 18 years, 36% male) provided ten daily ratings of their affective states for 6 consecutive days. The resulting time series were used to compute EWS in feeling down, listless, anxious, not relaxed, insecure, suspicious, and unwell. At baseline and 1-year follow-up, symptom severity was assessed by the Symptom Checklist-90 (SCL-90). We selected four subsamples of participants who reported an increase in one of the following SCL-90 domains: depression (N = 180), anxiety (N = 192), interpersonal sensitivity (N = 184), or somatic complaints (N = 166). Results Multilevel models showed that EWS in feeling suspicious anticipated increases in interpersonal sensitivity, as hypothesized. EWS were absent for other domains. While the association between EWS and symptom increases was restricted to the interpersonal sensitivity domain, post hoc analyses showed that symptom severity at baseline was related to heightened autocorrelations in congruent affective states for interpersonal sensitivity, depression, and anxiety. This pattern replicated in a second, independent dataset. Conclusions The presence of EWS prior to symptom shifts may depend on the dynamics of the psychopathological domain under consideration: for depression, EWS may manifest only several weeks prior to a shift, while for interpersonal sensitivity, EWS may already occur 1 year in advance. Intensive longitudinal designs where EWS and symptoms are assessed in real-time are required in order to determine at what timescale and for what type of domain EWS are most informative of future psychopathology.

Background: Adolescence is a period of both great social change, and of vulnerability to psychiatric distress. However, little is known about the associations between early psychopathology and social interactions at the fundamental level of daily life. To better understand the social correlates of subclinical psychopathology in adolescence, we assessed associations between general psychopathology and the quantity and quality of daily-life social interactions.& nbsp;Methods: During a six-day experience sampling period, adolescent and young adult participants in Study 1 (n = 663) and Study 2 (n = 1027) reported the quantity and quality of their everyday social interactions. General psychopathology was assessed using the Symptom Checklist-90 and Brief Symptom Inventory-53. The rela-tionship between psychopathology and each outcome variable was tested in separate multilevel linear and lo-gistic regression models.& nbsp;Results: General psychopathology was associated with social interaction quality. Associations between psychopa-thology and the number of social interactions were less apparent: In Study 1, participants with more psychopa-thology were not more alone, whereas Study 2 participants with higher levels of psychopathology were alone more. Limitations: Limitations include no separate investigation of distinct types of psychopathology, and relatively low compliance to the experience sampling in Study 2.& nbsp;Conclusions: Consistent associations between subclinical psychopathology and the quality of social interactions support the fundamentally social nature of early psychopathology. Moreover, negative experiences of social interactions may be more valuable markers of early psychopathology than a reduced quantity of social behaviors. Conceptualizations of daily-life social functioning, and prevention/intervention efforts would benefit from a greater consideration of the quality of everyday social experiences.

Background Exposure to green space has beneficial effects on several cognitive and behavioral aspects. However, to our knowledge, no study addressed intelligence as outcome. We investigated whether the level of urbanicity can modify the association of residential green space with intelligence and behavior in children. Methods and findings This study includes 620 children and is part of the East Flanders Prospective Twin Survey (EFPTS), a registry of multiple births in the province of East Flanders, Belgium. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) in 620 children (310 twin pairs) between 7 and 15 years old. From a subset of 442 children, behavior was determined based on the Achenbach Child Behavior Checklist (CBCL). Prenatal and childhood residential addresses were geocoded and used to assign green space indicators. Mixed modeling was performed to investigate green space in association with intelligence and behavior while adjusting for potential confounding factors including sex, age, parental education, neighborhood household income, year of assessment, and zygosity and chorionicity. We found that residential green space in association with both intelligence and behavior in children was modified by the degree of urbanicity (p < 0.001). In children living in an urban environment, multivariable adjusted mixed modeling analysis revealed that an IQR increment of residential green space (3,000-m radius) was associated with a 2.6 points (95% CI 1.4–3.9; p < 0.001) higher total intelligence quotient (IQ) and 2.0 points (95% CI −3.5 to −0.4; p = 0.017) lower externalizing behavioral score. In children residing in a rural or suburban environment, no association was found. A limitation of this study is that no information was available on school location and the potential for unmeasured confounding (e.g., time spend outdoors). Conclusions Our results indicate that residential green space may be beneficial for the intellectual and the behavioral development of children living in urban areas. These findings are relevant for policy makers and urban planners to create an optimal environment for children to develop their full potential., Esmée M Bijnens and colleagues reveal beneficial effects of a green environment on a child's development and behaviour., Author summary Why was this study done? This study examines residential surrounding green space in association with intelligence and behavior in a study area that includes a spectrum of urban to rural environments. Previous studies mainly focused on urban areas, whereas only a few studies have explored differences in the effect of green space on cognition in nonurban settings. Understanding the health disparities that exist between urban and rural environments is essential for maintaining and improving human well-being in a rapidly urbanizing world. What did the researchers do and find? This longitudinal birth cohort study of twins assessed intelligence in 620 children between 7 and 15 years old. Our results indicate that residential green space is especially beneficial for intellectual and behavioral development of children living in an urban environment. What do these findings mean? We show that low residential green space in urban children is associated with a “shift” towards a higher incidence of low IQ demonstrating the public health impact of our findings.

BACKGROUND: The temporal dynamics of cortisol may be altered in depression. Optimally studying these dynamics in daily life requires specific analytical methods. We used a continuous-time multilevel process model to study set point (rhythm-corrected mean), variability around this set point, and regulation strength (speed with which cortisol levels regulate back to the set point after any perturbation). We examined the generalizability of the parameters across two data sets with different sampling and assay methods, and the hypothesis that regulation strength, but not set point or variability thereof, would be altered in depressed, compared to non-depressed individuals.METHODS: The first data set is a general population sample of female twins (n = 523), of which 21 were depressed, with saliva samples collected 10 times a day for 5 days. The second data set consists of pair-matched clinically depressed and non-depressed individuals (n = 30), who collected saliva samples 3 times a day for 30 days. Set point, regulation strength and variability were examined using a Bayesian multilevel Ornstein-Uhlenbeck (OU) process model. They were first compared between samples, and thereafter assessed within samples in relation to depression.RESULTS: Set point and variability of salivary cortisol were twice as high in the female twin sample, compared to the pair-matched sample. The ratio between set point and variability, as well as regulation strength, which are relative measures and therefore less affected by the specific assay method, were similar across samples. The average regulation strength was high; after an increase in cortisol, cortisol levels would decrease by 63 % after 10 min, and by 95 % after 30 min, but depressed individuals of the pair-matched sample displayed an even faster regulation strength.CONCLUSIONS: The OU process model recovered similar cortisol dynamics for the relative parameters of the two data sets. The results suggest that regulation strength is increased in depressed individuals. We recommend the presented methodology for future studies and call for replications with more diverse depressed populations.

Introduction There is growing evidence that mental disorders behave like complex dynamic systems. Complex dynamic systems theory states that a slower recovery from small perturbations indicates a loss of resilience of a system. This study is the first to test whether the speed of recovery of affect states from small daily life perturbations predicts changes in psychopathological symptoms over 1 year in a group of adolescents at increased risk for mental disorders. Methods We used data from 157 adolescents from the TWINSSCAN study. Course of psychopathology was operationalized as the 1-year change in the Symptom Checklist-90 sum score. Two groups were defined: one with stable and one with increasing symptom levels. Time-series data on momentary daily affect and daily unpleasant events were collected 10 times a day for 6 days at baseline. We modeled the time-lagged effect of daily unpleasant events on negative and positive affect after each unpleasant event experienced, to examine at which time point the impact of the events is no longer detectable. Results There was a significant difference between groups in the effect of unpleasant events on negative affect 90 min after the events were reported. Stratified by group, in the Increase group, the effect of unpleasant events on both negative (B = 0.05, p B = − 0. 08, p Conclusion Findings cautiously suggest that adolescents who develop more symptoms in the following year may display a slower affect recovery from daily perturbations at baseline. This supports the notion that mental health may behave according to the laws of a complex dynamic system. Future research needs to examine whether these dynamic indicators of system resilience may prove valuable for personalized risk assessment in this field.

Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; Magnusson, Patrik KE/0000-0002-7315-7899; ONCEL, Sevgi YURT/0000-0002-0990-292X; Aliev, Fazil/0000-0001-8357-4699; Silventoinen, Karri/0000-0003-1759-3079; van Beijsterveldt, Toos/0000-0002-6617-4201; Knafo-Noam, Ariel/0000-0003-0613-1960; Latvala, Antti/0000-0001-5695-117X; Loos, Ruth/0000-0002-8532-5087; Bartels, Meike/0000-0002-9667-7555; Sund, Reijo/0000-0002-6268-8117; Willemsen, Gonneke/0000-0003-3755-0236 WOS:000560040700031 PubMed: 32409744 Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis. Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF-projects)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Swedish Research CouncilSwedish Research Council [2017-00641]; Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO) [904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008]; European Research CouncilEuropean Research Council (ERC); Avera Institute, Sioux Falls, South Dakota (USA); KNAW Academy Professor Award [PAH/6635]; ENGAGE - European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 308248, 312073, 264146]; Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); Cancer Research UKCancer Research UK [C1418/A7974]; European UnionEuropean Union (EU) [HEALTH-F4-2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433, POCI/DES/56834/2004]; Portuguese agency for research (The Foundation for Science and Technology [FCT]); Krkkale University Research Grant: KKU [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Osaka University's International Joint Research Promotion Program [R01 HD068435, R01 MH062375]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; California Twin Program; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Carolina African American Twin Study of Aging - National Institute on Aging [1RO1-AG13662-01A2, DA011015, 5T32DA017637, 5T32AG052371]; Michigan State University [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-HD066040]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [11-SPG-2518]; MSU Foundation - National Institute of Mental Health [R01 MH58354, AA023322, HD081437]; Vietnam Era Twin Study of Aging; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; West Japan Twins and Higher Order Multiple Births Registry [15H05105]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Centre of Research Excellence Grant [1079102]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [240994]; [266592] This study was conducted within the CODATwins project (Academy of Finland #266592). The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; Amsterdam Public Health (APH); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA) and the KNAW Academy Professor Award (PAH/6635) to DIB. Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278, 308248, 312073 and 264146 to J Kaprio). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413, and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). S.Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. Colorado Twin Registry is funded byNIDA funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371.; The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the National Institutes of Health. Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo.

Loos, Ruth J F/0000-0002-8532-5087; Huibregtse, Brooke M./0000-0003-0977-7249; Kandler, Christian/0000-0002-9175-235X; Hjelmborg, Jacob/0000-0001-9630-9149; mangino, massimo/0000-0002-2167-7470; Siribaddana, Sisira/0000-0001-5821-2557; Plomin, Robert/0000-0002-0756-3629; Latvala, Antti/0000-0001-5695-117X; Kaprio, Jaakko/0000-0002-3716-2455; Willemsen, Gonneke/0000-0003-3755-0236; Tan, Qihua/0000-0003-3194-0030; Pahlen, Shandell/0000-0003-0753-4155; Pedersen, Nancy/0000-0001-8057-3543; Haworth, Claire/0000-0002-8608-289X; Nistico, Lorenza/0000-0003-1805-6240; Skytthe, Axel/0000-0002-8629-4913; van Beijsterveldt, Toos/0000-0002-6617-4201; Rebato, Esther/0000-0003-1221-8501; Li, Lintao/0000-0002-0604-9660; Bartels, Meike/0000-0002-9667-7555; Silventoinen, Karri/0000-0003-1759-3079; Cunha Oliveira, Vinicius/0000-0002-8658-3774; Sund, Reijo/0000-0002-6268-8117; Sodemann, Morten/0000-0001-8992-2500; Rasmussen, Finn/0000-0001-7915-7809; Harden, Kathryn/0000-0002-1557-6737; Medda, Emanuela/0000-0003-4837-4549; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Colodro Conde, Lucia/0000-0002-9004-364X WOS: 000517442200060 PubMed: 31364586 The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m(2)) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Centre of Research Excellence Grant from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, R21 AG039572]; National Medical Research Council Research Fellowship; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, FlandersFWO; ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Cancer Research UKCancer Research UK [C1418/A7974]; W T Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths, University of London; UK Medical Research CouncilMedical Research Council UK (MRC) [MR/M021475/1, G0901245]; National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AG053217, RC2 HL103416]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01, 1R01-MH118848-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; European Research CouncilEuropean Research Council (ERC) [ERC-230374]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government; Portuguese agency for research (The Foundation for Science and Technology [FCT]) [POCI/DES/56834/2004]; Wellcome TrustWellcome Trust; Medical Research CouncilMedical Research Council UK (MRC); European UnionEuropean Union (EU); National Institute for Health Research (NIHR)National Institute for Health Research (NIHR); King's College London; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; Swedish Research CouncilSwedish Research Council [2017-00641]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; MRCMedical Research Council UK (MRC) [MR/M021475/1]; Krkkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; Stockholm County Council (ALF-projects)Stockholm County Council; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); [5T32DA017637]; [5T32AG052371] This study was conducted within the CODATwins project (Academy of Finland #266592). K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. Paulo Ferreira is funded by a National Medical Research Council Research Fellowship. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01).; The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation.; Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA-funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145 and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the W T Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory, who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. T. C. Eley is partly funded by a program grant from the UK Medical Research Council (MR/M021475/1).; This study presents independent research [partly] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Minnesota Twin Registry (MTR) acknowledges support from NIH grant R01AG053217. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 and 1R01-MH118848-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) and 11-SPG-2518 from the MSU Foundation. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD or the National Institutes of Health. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government's Operational Infrastructure Support Program.; Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). TwinsUK receives funding from the Wellcome Trust, Medical Research Council and European Union.; TwinsUK and M. Mangino are supported by the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no. 2017-00641.; The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). Currently TEDS is supported by MRC grant 'MR/M021475/1'. The Texas Twin Project is currently funded by grant R01HD083613 from the National Institutes of Health. S. Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381 and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

Background: Developmental processes in the placenta and the fetal brain are shaped by the similar biological signals. Evidence accumulates that adaptive responses of the placenta may infuence central nervous system development. We hypothesize that placental mtDNA content at birth is associated with intelligence in childhood. In addition, we investigate if intra-pair diferences in mtDNA content are associated with intra-pair diferences in intelligence. Methods: Relative mtDNA content was measured using qPCR in placental tissue of 375 children of the East Flanders Prospective Twin Survey. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) between 8 and 15 years old. We accounted for sex, gestational age, birth weight, birth year, zygosity and chorionicity, cord insertion, age at measurement, indicators of socioeconomic status, smoking during pregnancy, and urban environment. Results: In multivariable adjusted mixed modelling analysis, each doubling in placental mtDNA content was associated with 2.0 points (95% CI 0.02 to 3.9; p=0.05) higher total and 2.3 points (95% CI 0.2 to 4.3; p=0.03) higher performance IQ in childhood. We observed no association between mtDNA content and verbal intelligence. Intra-pair diferences in mtDNA content and IQ were signifcantly (p=0.01) correlated in monozygotic-monochorionic twin pairs, showing that the twin with the highest mtDNA content was 1.9 times more likely (p=0.05) to have the highest IQ. This was not observed in dichorionic twin pairs. Conclusions: We provide the frst evidence that placental mtDNA content is associated with childhood intelligence. This emphasizes the importance of placental mitochondrial function during in utero life on fetal brain development with long-lasting consequences Dr. Bijnens holds a fellow-ship from the Marguerite-Marie Delacroix foundation. Bram Janssen is a postdoctoral fellow of the Research Foundation Flanders (FWO). Mitochondrial DNA measurements were covered by a grant of FWO (G073315N). Since its start, the East Flanders Prospective Twin Survey has been partly supported by grants from the Fund of Scientifc Research Flanders and Twins, a non-proft Association for Scientifc Research in Multiple Births (Belgium). The funding source had no involvement in any activities related to study design, collection, analysis and interpretation of data presented in this manuscript, writing of the report or in the decision to submit the article for publication.

Purpose: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology.Methods: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model.Results: Linear analyses showed that emotional stress reactivity was not associated with onset (β = .02; P = .56) or persistence (β = −.01; P = .78) of symptoms. There was a significant effect of baseline symptom score (β = .53; P β = .19; P β = .25; P β = −.03; P = .65) or severe (β = −.06; P = .42), stressors was associated with symptom persistence one year later.Discussion: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

Background: Previous research shows that, besides risk factors in adult life, the early-life environment can influence blood pressure and hypertension in adults. However, the effects of residential traffic exposure and residential greenness in the early-life on blood pressure in young adulthood are currently unknown. Methods: Ambulatory (24-h) blood pressures of 278 twins (132 pairs) of the East Flanders Prospective Twins Study were obtained at the age of 18 to 25 years. Prenatal and adulthood residential addresses were geocoded and used to assign prenatal and postnatal traffic and greenness indicators. Mixed modelling was performed to investigate blood pressure in association with greenness while adjusting for potential confounding factors. Results: Night-time systolic blood pressure was inversely associated with greenness at the residential address in twins living at the same address their entire life (non-movers, n = 97, 34.9%). An interquartile increase in residential greenness exposure (1000 m radius) was associated with a 3.59 mmHg (95% CI: -6.0 to -1.23; p = 0.005) lower adult night systolic blood pressure. Among twins who were living at a different address than their birth address at time of the measurement (n = 181, 65.1%), night-time blood pressure was inversely associated with residential surrounding greenness at adult age as well as with residential greenness in early-life. However after additional adjustment for residential greenness exposure in adulthood, only residential greenness exposure in early-life was significantly associated with night systolic blood pressure. While no significant effect of adult residential greenness with adult blood pressure was observed, while accounting for the early-life greenness exposure. Conclusions: Lower residential greenness in the early-life environment was independently associated with a higher adult blood pressure. This indicates that residential greenness has persistent effects on blood pressure. This investigation is supported by the EU research council "project ENVIRONAGE" (ERC-2012-StG 310,890) and Flemish Scientific Fund (G073315 N). Since its start, the East Flanders Prospective Twin Study has been partly supported by grants from the Fund of Scientific Research Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium).

Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n = 808, sample 1) and a female twin sample (n = 621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field.

Background: Converging evidence supports childhood trauma as possible causal risk for psychosis and related psychopathology. However, studies have shown that baseline psychotic symptoms may actually increase risk for subsequent victimization, suggesting that exposure to CT is not random but may result from pre-existing vulnerability. Therefore, studies testing whether the association between CT and psychopathology persists when accounting for gene-environment correlation are much needed.Methods: A monozygotic (MZ) twin differences approach was used to examine whether differences in CT exposure among MZ twin pairs would be associated with MZ differences in symptoms. As MZ twins are genetically identical, within-pair correlations between CT exposure and psychopathology rule out the possibility that the association is solely attributable to gene-environment correlation. 266 monozygotic twins (133 pairs) from a larger general population study were available for analysis.Results: CT was associated with symptoms of psychosis (B = 0.62; SE = 0.08, p Conclusion: While it is not unlikely that pre-existing vulnerability may increase the risk for traumatic exposures, such gene-environment correlation does not explain away the association between CT and psychopathology. The present findings thus suggest that at least part of the association between CT and psychopathology may be causal. (C) 2018 Elsevier B.V. All rights reserved.

Kandler, Christian/0000-0002-9175-235X; Bartels, Meike/0000-0002-9667-7555; Medland, Sarah E/0000-0003-1382-380X; Kaprio, Jaakko/0000-0002-3716-2455; Fagnani, Corrado/0000-0001-5771-7772; de Freitas, Duarte Luis/0000-0001-6642-3370; Hjelmborg, Jacob/0000-0001-9630-9149; mangino, massimo/0000-0002-2167-7470; Busjahn, Andreas/0000-0001-9650-6919; Montgomery, Grant W/0000-0002-4140-8139; Moller, Soren/0000-0003-0858-4269; Heikkila, Kauko/0000-0002-9256-8028; Skytthe, Axel E/0000-0002-8629-4913; Christensen, Kaare/0000-0002-5429-5292; Knafo-Noam, Ariel/0000-0003-0613-1960; ONCEL, Sevgi YURT/0000-0002-0990-292X; Sund, Reijo/0000-0002-6268-8117; Aliev, Fazil/0000-0001-8357-4699; Magnusson, Patrik/0000-0002-7315-7899; Huibregtse, Brooke M./0000-0003-0977-7249; Loos, Ruth J F/0000-0002-8532-5087; Boivin, Michel/0000-0001-8621-9844; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Pahlen, Shandell/0000-0003-0753-4155; van Beijsterveldt, Toos/0000-0002-6617-4201; McAdams, Tom/0000-0002-6825-3499; Sodemann, Morten/0000-0001-8992-2500; Pedersen, Nancy/0000-0001-8057-3543; Derom, Catherine/0000-0001-5574-796X; Plomin, Robert/0000-0002-0756-3629; Rebato, Esther/0000-0003-1221-8501; Saffery, Richard/0000-0002-9510-4181; Harden, Kathryn/0000-0002-1557-6737; Willemsen, Gonneke/0000-0003-3755-0236; Aaltonen, Sari/0000-0002-2873-4263; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Haworth, Claire/0000-0002-8608-289X; Llewellyn, Clare/0000-0002-0066-2827 WOS: 000381870200017 PubMed: 27413137 Background: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. Objectives: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. Design: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. Results: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. Conclusions: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity. CODATwins project (Academy of Finland) [266592]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, HD081437, AA023322, RC2 HL103416]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease; Velux Foundation; US NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4 [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease Genetics grantAcademy of Finland [213506, 129680]; Academy of Finland grantAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Cancer Research UKCancer Research UK [C1418/A7974]; W T Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research Fellowship grant [RF/2/RFG/2008/0145]; Goldsmiths, University of London, United Kingdom; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Medexpert Ltd., Budapest, Hungary; European Research CouncilEuropean Research Council (ERC) [240994, 230374]; Michigan State University; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; MagW/ZonMW grant [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464- 14192]; VU University's Institute for Health and Care Research; Avera Institute, Sioux Falls, SD; Australian National Health and Medical Research Council grantNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children grant [032-2007]; Victorian Government's Operational Infrastructure Support Program; Portuguese agency for research (The Foundation for Science and Technology) [POCI/DES/56834/2004]; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research Council grant [31/D19086]; Kirikkale University Research grantKirikkale University [KKU 2009/43]; TUBITAK grantTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; European CommunityEuropean Community (EC); National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, United Kingdom; National Institute of Mental Health grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; [5T32DA017637-11]; Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515] This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: The Boston University Twin Project is funded by grants R01 HD068435 and R01 MH062375 from the NIH to KS. California Twin Program was supported by The California Tobacco-Related Disease Research Program grants 7RT-0134H, 8RT-0107H, and 6RT-0354H and by NIH grant 1R01ESO15150-01. Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA funded center grant DA011015, and Longitudinal Twin Study HD10333; BMH is supported by to 5T32DA017637-11. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US NIH grant P01 AG08761. Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; National Institute of Alcohol Abuse and Alcoholism grants AA-12502, AA-00145, and AA-09203 to RJR; the Academy of Finland Center of Excellence in Complex Disease Genetics grants 213506 and 129680; and the Academy of Finland grants 100499, 205585, 118555, 141054, 265240, 263278, and 264146 to JK. KS is supported by Osaka University's International Joint Research Promotion Program. Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the W T Grant Foundation, the University of London Central Research fund and Medical Research Council Training Fellowship grant G81/343 and Career Development Award G120/635 to TCE. Wave 4 was supported by the Economic and Social Research Council grant RES-000-22-2206 and the Institute of Social Psychiatry (06/07-11) to AMG, who was also supported at that time by a Leverhulme Research Fellowship grant RF/2/RFG/2008/0145. Wave 5 was supported by funding to AMG from Goldsmiths, University of London, United Kingdom. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China grant 81125007. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Longitudinal Israeli Study of Twins was funded by the Starting Grant 240994 from the European Research Council to AK. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, and R03-MH63851-01 from the National Institute of Mental Health, R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and 11-SPG-2518 from the MSU Foundation. The NAS-NRC Twin Registry acknowledges financial support from NIH grant R21 AG039572. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, and 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464- 14192; VU University's Institute for Health and Care Research; the European Research Council grant 230374; and the Avera Institute, Sioux Falls, SD.; PETS was supported by the Australian National Health and Medical Research Council grant 437015 and 607358 to JC and RS, the Bonnie Babes Foundation grant BBF20704 to JMC, the Financial Markets Foundation for Children grant 032-2007 to JMC, and by the Victorian Government's Operational Infrastructure Support Program. Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology). The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (MB). South Korea Twin Registry is supported by National Research Foundation of Korea grant NRF-371-2011-1 B00047. The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the NIH. The Twins Early Development Study is supported by program grant G0901245 from the UK Medical Research Council and the work on obesity in the Twins Early Development Study is supported in part by the UK Biotechnology and Biological Sciences Research Council grant 31/D19086. SYO and FA are supported by Kirikkale University Research grant KKU 2009/43 and TUBITAK grant 114C117. TwinsUK was funded by European Community's Seventh Framework Programme grant FP7/2007-2013. The study also receives support from the National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, United Kingdom. The University of Southern California Twin Study is funded by the National Institute of Mental Health grant R01 MH58354. University of Washington Twin Registry was supported in part by grant NIH RC2 HL103416 (D and PI). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) grant 15H05105 from the Japan Society for the Promotion of Science.

Meta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.

Adolescents and young adults are highly focused on peer evaluation, but little is known about sources of their differential sensitivity. We examined to what extent sensitivity to peer evaluation is influenced by interacting environmental and genetic factors. A sample of 354 healthy adolescent twin pairs (n = 708) took part in a structured, laboratory task in which they were exposed to peer evaluation. The proportion of the variance in sensitivity to peer evaluation due to genetic and environmental factors was estimated, as was the association with specific a priori environmental risk factors. Differences in sensitivity to peer evaluation between adolescents were explained mainly by non-shared environmental influences. The results on shared environmental influences were not conclusive. No impact of latent genetic factors or gene-environment interactions was found. Adolescents with lower self-rated positions on the social ladder or who reported to have been bullied more severely showed significantly stronger responses to peer evaluation. Not genes, but subjective social status and past experience of being bullied seem to impact sensitivity to peer evaluation. This suggests that altered response to peer evaluation is the outcome of cumulative sensitization to social interactions. ispartof: Child Psychiatry and Human Development vol:49 issue:5 pages:766-779 ispartof: location:United States status: published

Childhood trauma exposure has been associated with a clinically relevant mixed phenotype of psychopathology composed of depressive, anxiety, and psychosis symptoms, across healthy and clinical samples. Altered stress reactivity after exposure to childhood trauma may be a plausible underlying mechanism explaining this association. In a general population sample of female twins (T0 = 564; T1 = 483), associations between childhood trauma exposure and symptom profile (no symptoms, isolated symptoms, or a mixed phenotype) on the one hand, and daily life stress reactivity on the other were investigated. Daily life stress reactivity was measured using the Experience Sampling Method (ESM), and was defined as negative affect reactivity to minor daily life stressors. Individuals exposed to childhood trauma who reported a mixed phenotype of psychopathology showed a significant increase in emotional reactivity to daily life stress (activity and social stress), compared with trauma-exposed individuals without a mixed phenotype. In the trauma-exposed mixed phenotype group, increased emotional reactivity to event-stress predicted more severe symptoms at +/- 14 month follow-up. This study found evidence that may link heightened emotional reactivity to stress in individuals with a trauma history to the risk for later comorbid psychopathology.

Loos, Ruth J F/0000-0002-8532-5087; Sund, Reijo/0000-0002-6268-8117; Busjahn, Andreas/0000-0001-9650-6919; Tan, Qihua/0000-0003-3194-0030; Aliev, Fazil/0000-0001-8357-4699; Kaprio, Jaakko/0000-0002-3716-2455; Magnusson, Patrik/0000-0002-7315-7899; Tan, Qihua/0000-0003-3194-0030; ONCEL, Sevgi YURT/0000-0002-0990-292X; Ordonana, Juan R./0000-0001-7779-6017; Colodro-Conde, Lucia/0000-0002-9004-364X; Huibregtse, Brooke M./0000-0003-0977-7249; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; Rebato, Esther/0000-0003-1221-8501; Pedersen, Nancy/0000-0001-8057-3543; Latvala, Antti/0000-0001-5695-117X; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Piirtola, Maarit/0000-0001-7270-6676 WOS: 000438457400025 PubMed: 30001359 Background Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background. Methods and findings The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18-69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m(2) lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m(2) lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m(2) higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m(2) higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ cotwins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m(2), 95% CI 0.04, 0.23 among men; -0.04 kg/m(2), 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade. Conclusions Smoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m(2). Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); ENGAGE - European Network for Genetic and Genomic Epidemiology [FP7- HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Sigrid Juselius FoundationSigrid Juselius Foundation; Osaka University's International Joint Research Promotion Program; Medexpert Ltd., Budapest, Hungary; European Union's Seventh Framework Programmes ENGAGE ConsortiumEuropean Union (EU) [HEALTH-F4- 2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433]; Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; Centre of Research Excellence grant from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia; Australian Research CouncilAustralian Research Council; Australian National Health and Medical Research Council fellowshipNational Health and Medical Research Council of Australia [SRFB-1103623]; National Institutes of Health grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study [HD10333]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; Global Research Network Program of the National Research Foundation [NRF 2011-220- E00006]; Kirikkale University Research Grant: KKUKirikkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; [5T32DA017637]; [5T32AG052371] This study was conducted within the CODATwins project (Academy of Finland grant #266592 to KS). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7- HEALTH-F4-2007 (grant agreement number 201413), National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to RJ Rose), the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to JK). JK also acknowledges support from the Sigrid Juselius Foundation. KS is supported by Osaka University's International Joint Research Promotion Program. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4- 2007-201413), and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The Australian Twin Registry is supported by a Centre of Research Excellence grant (ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The QIMR twin study acknowledges grants from the Australian National Health and Medical Research Council and the Australian Research Council. SM is supported by an Australian National Health and Medical Research Council fellowship (SRFB-1103623). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. The Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources from the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The Colorado Twin Registry is funded by NIDA-funded center grant DA011015 and Longitudinal Twin Study HD10333; BH was supported by 5T32DA017637 and 5T32AG052371. The Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261). The Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220- E00006). SO and FA are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117.; None of the funders including HealthTwiSt GmbH and Pfizer Inc played a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries, excluding HealthTwiSt GmbH and Pfizer Inc, and/or research materials. The funder HealthTwiSt GmbH did not provide support in the form of salaries for authors (AB). HealthTwiSt GmbH collects data on twin samples and makes these available to academic researchers for a service fee to cover the costs (technical staff salaries and material costs). The funder (Pfizer Inc) did provide support in the form of consultation fees for authors (JK and TK) outside of the submitted work.

Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14-4.25 cm and 0.18-0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight. This work was supported by the Academy of Finland (grant number #266592). The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation. Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), Centre of Excellence in Research on Mitochondria, Metabolism and Disease (FinMIT, grant 272376), the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio and grant 266286 and 314383 to K Pietilainen), the Finnish Diabetes Research Foundation, Novo Nordisk Foundation, Helsinki University Central Hospital and University of Helsinki. K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. r 032-2007 to JMC), and by the Victorian Governments Operational Infrastructure Support Program. The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). The Twins Early Development Study (TEDS) is supported by a program grant (MR/M021475/1) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science. Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO +); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA).

Background: Telomere attrition is extremely rapid during the first years of life, while lifestyle during adulthood exerts a minor impact. This suggests that early life is an important period in the determination of telomere length. We investigated the importance of the early-life environment on both telomere tracking and adult telomere length. Methods: Among 184 twins of the East Flanders Prospective Twin Survey, telomere length in placental tissue and in buccal cells in young adulthood was measured. Residential addresses at birth and in young adulthood were geocoded and residential traffic and greenness exposure was determined. Results: We investigated individual telomere tracking from birth over a 20 year period (mean age (SD), 22.6 (3.1) years) in association with residential exposure to traffic and greenness. Telomere length in placental tissue and in buccal cells in young adulthood correlated positively (r = 0.31, P < 0.0001). Persons with higher placental telomere length at birth were more likely to have a stronger downward shift in telomere ranking over life (P < 0.0001). Maternal residential traffic exposure correlated inversely with telomere length at birth. Independent of birth placental telomere length, telomere ranking between birth and young adulthood was negatively and significantly associated with residential traffic exposure at the birth address, while traffic exposure at the residential address at adult age was not associated with telomere length. Conclusions: Longitudinal evidence of telomere length tracking from birth to adulthood shows inverse associations of residential traffic exposure in association with telomere length at birth as well as accelerated telomere shortening in the first two decades of life. This investigation is supported by the EU research council “project ENVIRONAGE” (ERC-2012-StG 310890), and the Flemish Scientific Fund (G073315N). Dr. Bijnens holds a fellow-ship from the Marguerite-Marie Delacroix foundation. Since its start, the East Flanders Prospective Twin Survey has been partly supported by grants from the Fund of Scientific Research Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium).

OBJECTIVESNighttime blood pressure (BP) has been shown to be superior to daytime BP in predicting hypertension related target organ damage and cardiac mortality. In our Georgia Cardiovascular Twin Study, we showed that apart from the genes that also influence daytime BP, specific genetic determinants explained 44% and 67% of the nighttime systolic BP (SBP) and diastolic BP (DBP) heritabilities, respectively. Here, we determined whether these results could be confirmed in a much larger twin cohort of young adults with 24-hour ambulatory BP measurements.METHODSAmbulatory BP was available in 703 white twins (308 pairs and 87 singletons, aged 18-34 years, 50% males) from the Prenatal Programming Twin Study. A bivariate quantitative genetic twin model was used to analyze daytime and nighttime BP. We conducted a meta-analysis to compare and integrate results from the 2 twin cohorts.RESULTSModel fitting showed no sex differences for any of the measures. Heritabilities were 0.60 and 0.51 for SBP and 0.54 and 0.46 for DBP at daytime and nighttime. The specific heritability due to novel genetic effects emerging during the nighttime was 0.21 for SBP and 0.26 for DBP, which comprised 41% and 57% of the total nighttime heritability for SBP and DBP, respectively. Meta-analysis confirmed absence of cohort differences with very similar combined results.CONCLUSIONSIn addition to genes that influence both daytime and nighttime BP, a large part of the heritability is explained by genes that specifically influence BP at night.

BackgroundAn association between white noise speech illusion and psychotic symptoms has been reported in patients and their relatives. This supports the theory that bottom-up and top-down perceptual processes are involved in the mechanisms underlying perceptual abnormalities. However, findings in nonclinical populations have been conflicting.ObjectivesThe aim of this study was to examine the association between white noise speech illusion and subclinical expression of psychotic symptoms in a nonclinical sample. Findings were compared to previous results to investigate potential methodology dependent differences.MethodsIn a general population adolescent and young adult twin sample (n = 704), the association between white noise speech illusion and subclinical psychotic experiences, using the Structured Interview for Schizotypy-Revised (SIS-R) and the Community Assessment of Psychic Experiences (CAPE), was analyzed using multilevel logistic regression analyses.ResultsPerception of any white noise speech illusion was not associated with either positive or negative schizotypy in the general population twin sample, using the method by Galdos et al. (2011) (positive: ORadjusted: 0.82, 95% CI: 0.6-1.12, p = 0.217; negative: ORadjusted: 0.75, 95% CI: 0.56-1.02, p = 0.065) and the method by Catalan et al. (2014) (positive: ORadjusted: 1.11, 95% CI: 0.79-1.57, p = 0.557). No association was found between CAPE scores and speech illusion (ORadjusted: 1.25, 95% CI: 0.88-1.79, p = 0.220). For the Catalan et al. (2014) but not the Galdos et al. (2011) method, a negative association was apparent between positive schizotypy and speech illusion with positive or negative affective valence (ORadjusted: 0.44, 95% CI: 0.24-0.81, p = 0.008).ConclusionContrary to findings in clinical populations, white noise speech illusion may not be associated with psychosis proneness in nonclinical populations.

Objective: Focusing on temporal associations between momentary (or state) loneliness, appraisal of social company, and being alone in daily life may help elucidate mechanisms that contribute to the development of prolonged (or trait) loneliness and major depressive disorder (MDD). We aim to examine if (a) a self-reinforcing loop between loneliness, negative appraisals of social company, and being alone in daily life may contribute to trait loneliness; (b) this possible self-reinforcing loop may also contribute to the development of MDD, by testing differences in temporal relationships between these social elements in participants who did or did not develop MDD during follow-up; and (c) any of these social elements at baseline predicted a MDD at follow-up. Methods: A female general population sample (n = 417) participated in an experience sampling method (ESM) study. Time-lagged analyses between loneliness, appraisal of social company, and being alone were examined at baseline, and their associations with the development of MDD during 20 months follow-up were investigated. Results: State loneliness was followed by an increase in negative appraisals of social company and a higher frequency of being alone. Further, negative appraisals of social company were associated with a higher frequency of being alone afterward. Only the latter was significant in the transition to MDD group. Trait loneliness predicted MDD during follow-up. Conclusions: Avoiding social contact after appraising company more negatively may contribute to the development of MDD.

A link between sleep and affect is well-known. Serotonin (5-HT) is associated with the regulation of affective as well as sleep-related processes. A functional polymorphism in the serotonin transporter gene (5-HTTLPR) has been associated with serotonergic functioning. The present study investigated whether allelic variation of this gene moderates the association between nighttime subjective sleep quality and affect the following day. A population-based sample of 361 ethnically homogenous adult female twins underwent a five day protocol based on the experience sampling method (ESM), assessing momentary negative affect, positive affect, and subjective sleep quality repeatedly and prospectively. There was a significant interaction between sleep quality and genotype in predicting positive affect the next day: carriers of one (n=167) or two S-alleles (n=78) had a significantly steeper slope compared to LL carriers (n=116) (chi(2)=4.16, p=.042 and chi(2)=3.90, p=.048 respectively). The association between subjective sleep quality and positive affect the next day varied as a function of 5-HTTLPR: it was stronger in carriers of at least one copy of the S-allele compared to homozygous L-carriers, supporting a link between sleep and affect regulation, in which serotonin may play a role. However, these results are preliminary and require replication.

BackgroundPoor sleep is a risk factor for depression, but little is known about the underlying mechanisms.AimsDisentangling potential mechanisms by which sleep may be related to depression by zooming downto the ‘micro-level’ of within-person daily life patterns of subjective sleep and affect usingthe experience sampling method (ESM).MethodA population-based twin sample consisting of 553 women underwent a 5-day baseline ESM protocolassessing subjective sleep and affect together with four follow-up assessments of depression.ResultsSleep was associated with affect during the next day, especially positive affect. Daytime negative affect was not associated with subsequent night-time sleep. Baseline sleep predicted depressive symptoms across the follow-up period.ConclusionsThe subtle, repetitive impact of sleep on affect on a daily basis, rather than the subtle repetitive impact of affect on sleep, may be one of the factors on the pathway to depression in women.

BackgroundFK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma.AimsTo examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype.MethodIn 401 general population twins, four functional polymorphisms were examined in models of psychosis and Cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder).ResultsThe most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and Cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma.ConclusionsTrauma may increase the risk of psychosis through enduring changes in the Cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Objectives: Blood pressure variability (BPV) and its reduction in response to antihypertensive treatment are predictors of clinical outcomes; however, little is known about its heritability. In this study, we examined the relative influence of genetic and environmental sources of variance of BPV and the extent to which it may depend on race or sex in young twins.Methods: Twins were enrolled from two studies. One study included 703 white twins (308 pairs and 87 singletons) aged 18-34 years, whereas another study included 242 white twins (108 pairs and 26 singletons) and 188 black twins (79 pairs and 30 singletons) aged 12-30 years. BPV was calculated from 24-h ambulatory blood pressure recording.Results: Twin modeling showed similar results in the separate analysis in both twin studies and in the meta-analysis. Familial aggregation was identified for SBP variability (SBPV) and DBP variability (DBPV) with genetic factors and common environmental factors together accounting for 18-40% and 23-31% of the total variance of SBPV and DBPV, respectively. Unique environmental factors were the largest contributor explaining up to 82-77% of the total variance of SBPV and DBPV. No sex or race difference in BPV variance components was observed. The results remained the same after adjustment for 24-h blood pressure levels.Conclusions: The variance in BPV is predominantly determined by unique environment in youth and young adults, although familial aggregation due to additive genetic and/or common environment influences was also identified explaining about 25% of the variance in BPV.

Background: Accelerated infant growth is associated with an al-tered, mostly adverse adult cardiometabolic risk profile. The impor-tance of genetic and environmental factors to these associations isunclear.Objective: The objective was to examine the importance of geneticand environmental factors in the associations between infant growthand adult cardiometabolic risk factors (anthropometrics, lipids, in-sulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.Design: Cardiometabolic risk factors were assessed in 240 twinpairs (aged 18–34 y) from the East Flanders Prospective Twin Sur-vey. Infant growth was defined as change in weight z score. Weregressed intrapair differences in growth during 4 growth windows(0–1, 1–6, 6–12, and 12–24 mo) against intrapair differences in therisk factors in monozygotic and dizygotic twins separately.Results: Within monozygotic twin pairs only, associations betweeninfant growth and most adult lipids, glucose, leptin, and blood pres-sure (eg, systolic blood pressure: b = 5.95 mm Hg per change inz score, P = 0.01 in monozygotic twins; b = 21.64, P = 0.82 indizygotic twins from 12 to 24 mo) were found. Within dizygotictwin pairs only, associations between growth and triglycerides andfibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score,P=0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotictwins from 0 to 1 mo) were identified. Most associations showeda detrimental effect of accelerated growth, but beneficial associa-tions were also identified (eg, total–to–high-density-lipoprotein cho-lesterol ratio: b = 20.22 per change in z score from 1 to 6 mo, P =0.008 in monozygotic twins).Conclusion: Our data showed that environmental factors play a rolein the associations between infant growth and most adult lipids,glucose, leptin, and blood pressure, whereas genetic factors are in-volved regarding triglycerides and fibrinogen. Am J Clin Nutrdoi: 10.3945/ajcn.112.039131.INTRODUCTIONCardiovascular disease is a major cause of mortality world-wide (1). The incidence of cardiovascular disease is increased inindividuals with an adverse cardiometabolic risk profile, whichincludes obesity, an unfavorable lipid profile, insulin resistance,and high blood pressure. It has become clear that besides theimportance of lifestyle, factors in early life are also involved inthe development of this risk profile. Low birth weight is relatedto an adverse cardiometabolic risk profile and cardiovasculardisease later in life (2–4). In addition, subsequent acceleratedpostnatal growth has been proposed as a mechanism that linkslow birth weight to an unfavorable cardiometabolic risk profile(5, 6). Growth during infancy (mostly defined as 0–2 y) has beenpositively associated with obesity (7), hypertension (8), an ad-verse cardiometabolic risk profile (9), and metabolic syndrome(10). On the contrary, there is also some evidence that slowinfant growth is associated with certain harmful cardiometabolicoutcomes in adulthood, eg, regarding lipids (11, 12), insulin re-sistance (13, 14), and stroke (15).Importantly, to regard “infancy” as one growth window from0 to 2 y may be too broad a definition. For example, it wasreported that the first 3 mo of life may be most important for thedevelopment of an adverse cardiometabolic risk profile (16). Inaddition, accelerated growth in the first 2 wk of life is relatedto adult endothelial dysfunction, a precursor of atherosclerosis

Loos, Ruth J F/0000-0002-8532-5087; Huibregtse, Brooke M./0000-0003-0977-7249; Busjahn, Andreas/0000-0001-9650-6919; Skytthe, Axel E/0000-0002-8629-4913; Heikkila, Kauko/0000-0002-9256-8028; Haworth, Claire/0000-0002-8608-289X; Hjelmborg, Jacob/0000-0001-9630-9149; Sund, Reijo/0000-0002-6268-8117; Aliev, Fazil/0000-0001-8357-4699; Fagnani, Corrado/0000-0001-5771-7772; Kaprio, Jaakko/0000-0002-3716-2455; Knafo-Noam, Ariel/0000-0003-0613-1960; Montgomery, Grant W/0000-0002-4140-8139; Moller, Soren/0000-0003-0858-4269; ONCEL, Sevgi YURT/0000-0002-0990-292X; Duncan, Glen/0000-0001-6909-1869; Medland, Sarah E/0000-0003-1382-380X; Kandler, Christian/0000-0002-9175-235X; Christensen, Kaare/0000-0002-5429-5292; Magnusson, Patrik/0000-0002-7315-7899; mangino, massimo/0000-0002-2167-7470; Bartels, Meike/0000-0002-9667-7555; de Freitas, Duarte Luis/0000-0001-6642-3370; Harden, Kathryn/0000-0002-1557-6737; Derom, Catherine/0000-0001-5574-796X; Plomin, Robert/0000-0002-0756-3629; Silventoinen, Karri/0000-0003-1759-3079; Rasmussen, Finn/0000-0001-7915-7809; Boivin, Michel/0000-0001-8621-9844; Saffery, Richard/0000-0002-9510-4181; Pahlen, Shandell/0000-0003-0753-4155; van Beijsterveldt, Toos/0000-0002-6617-4201; Rebato, Esther/0000-0003-1221-8501; Pedersen, Nancy/0000-0001-8057-3543; Aaltonen, Sari/0000-0002-2873-4263; Llewellyn, Clare/0000-0002-0066-2827; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Sodemann, Morten/0000-0001-8992-2500; Willemsen, Gonneke/0000-0003-3755-0236; D'Ippolito, Cristina/0000-0001-7902-9380; McAdams, Tom/0000-0002-6825-3499 WOS: 000378317900001 PubMed: 27333805 Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments. Academy of FinlandAcademy of Finland [266592, 100499, 205585, 118555, 141054, 265240, 263278, 264146]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, AA023322, HD081437, R21 AG039572]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; Special Fund for Health Scientific Research in the Public Welfare, China [201502006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015, HD10333]; National Program for Research Infrastructure from the Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, Flanders and Twins; NGAGE-European Network for Genetic and Genomic Epidemiology [FP7-HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Osaka University's International Joint Research Promotion Program; Cancer Research UKCancer Research UK [C1418/A7974]; WT Grant Foundation; University of London Central Research fund; Medical Research Council Training FellowshipMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths, University of London; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Medexpert Ltd., Budapest, Hungary; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; VU University's Institute for Health and Care Research (EMGO+); European Research CouncilEuropean Research Council (ERC) [ERC-230374]; Avera Institute, Sioux Falls, South Dakota (USA); Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government's Operational Infrastructure Support Program; Portuguese agency for research (The Foundation for Science and Technology [FCT]) [POCI/DES/56834/2004]; Fonds Quebecois de la Recherche sur la Societe et la CultureFQRNT; Fonds de la Recherche en Sante du QuebecFonds de la Recherche en Sante du Quebec; Social Science and Humanities Research Council of Canada; National Health Research Development Program; Canadian Institutes for Health ResearchCanadian Institutes of Health Research (CIHR); Sainte-Justine Hospital's Research Center; Canada Research Chair ProgramCanada Research Chairs; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; Kirikkale University Research Grant: KKUKirikkale University [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Wellcome TrustWellcome Trust; European Community's Seventh Framework Programme (FP7)European Union (EU); National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RC2 HL103416]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; [5T32DA017637-11]; Medical Research CouncilMedical Research Council UK (MRC) [G19/2, MR/M021475/1, G120/635, G0500079, G0901245]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515] This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). Chinese National Twin Registry is funded by Special Fund for Health Scientific Research in the Public Welfare (Project No: 201502006), China. Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longitudinal Twin Study HD10333; Author Huibregtse is supported by to 5T32DA017637-11. Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to RJ Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J. Kaprio). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Waves 1-3 of Genesis 12-19 were funded by the WT Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572.; Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to J. C. and R.S.), the Bonnie Babes Foundation (grant number BBF20704 to J. M. C.), the Financial Markets Foundation for Children (grant no. 032-2007 to J. M. C.), and by the Victorian Government's Operational Infrastructure Support Program. Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness and health: the Madeira family study Project reference: POCI/DES/56834/2004 Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). The Quebec Newborn Twin Study acknowledges financial support from the Fonds Quebecois de la Recherche sur la Societe et la Culture, the Fonds de la Recherche en Sante du Quebec, the Social Science and Humanities Research Council of Canada, the National Health Research Development Program, the Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the Canada Research Chair Program (Michel Boivin). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the National Institutes of Health. The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). S.Y. Oncel and F. Aliev are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science.

Previous research has established the comorbidity of adult Attention-Deficit Hyperactivity Disorder (ADHD) with different personality disorders including Borderline Personality Disorder (BPD). The association between adult ADHD and BPD has primarily been investigated at the phenotypic level and not yet at the genetic level. The present study investigates the genetic and environmental contributions to the association between borderline personality traits (BPT) and ADHD symptoms in a sample of 7,233 twins and siblings (aged 18-90 years) registered with the Netherlands Twin Register and the East Flanders Prospective Twin Survey (EFPTS) Participants completed the Conners' Adult ADHD Rating Scales (CAARS-S:SV) and the Personality Assessment Inventory-Borderline Features Scale (PAI-BOR). A bivariate genetic analysis was performed to determine the extent to which genetic and environmental factors influence variation in BPT and ADHD symptoms and the covariance between them. The heritability of BPT and ADHD symptoms was estimated at 45 and 36%, respectively. The remaining variance in BPT and ADHD symptoms was explained by unique environmental influences. The phenotypic correlation between BPT and ADHD symptoms was estimated at r=0.59, and could be explained for 49% by genetic factors and 51% by environmental factors. The genetic and environmental correlations between BPT and ADHD symptoms were 0.72 and 0.51, respectively. The shared etiology between BPT and ADHD symptoms is thus a likely cause for the comorbidity of the two disorders. © 2011 Wiley-Liss, Inc.

BackgroundTraumatic life events are generally more common in patients with borderline personality disorder (BPD) than in non-patients or patients with other personality disorders. This study investigates whether exposure to life events moderates the genetic architecture of BPD features. As the presence of genotype–environment correlation (rGE) can lead to spurious findings of genotype–environment interaction (G×E), we also test whether BPD features increase the likelihood of exposure to life events.MethodThe extent to which an individual is at risk to develop BPD was assessed with the Personality Assessment Inventory – Borderline features scale (PAI-BOR). Life events under study were a divorce/break-up, traffic accident, violent assault, sexual assault, robbery and job loss. Data were available for 5083 twins and 1285 non-twin siblings. Gene–environment interaction and correlation were assessed by using structural equation modelling (SEM) and the co-twin control design.ResultsThere was evidence for both gene–environment interaction and correlation. Additive genetic influences on BPD features interacted with the exposure to sexual assault, with genetic variance being lower in exposed individuals. In individuals who had experienced a divorce/break-up, violent assault, sexual assault or job loss, environmental variance for BPD features was higher, leading to a lower heritability of BPD features in exposed individuals. Gene–environment correlation was present for some life events. The genes that influence BPD features thus also increased the likelihood of being exposed to certain life events.ConclusionsTo our knowledge, this study is the first to test the joint effect of genetic and environmental influences and the exposure to life events on BPD features in the general population. Our results indicate the importance of both genetic vulnerability and life events.

Objective Daily life affective responses are closely linked to vulnerability and resilience in depression. Prediction of future clinical course may be improved if information on daily life emotional response patterns is taken into account. Method Female subjects with a history of major depression ( n = 83), recruited from a population twin register, participated in a longitudinal study using momentary assessment technology with 4 follow-up measurements. The effect of baseline daily life emotional response patterns (affect variability, stress-sensitivity and reward experience) on follow-up depressive symptomatology was examined. Results Both reward experience ( B = −0.30, p = 0.001) and negative affect variability ( B = 0.46, p = 0.001) predicted future negative affective symptoms independent of all other dynamic emotional patterns and conventional predictors. Conclusion Daily life information on dynamic emotional patterns adds to the prediction of future clinical course, independent of severity of symptoms and neuroticism score. Better prediction of course may improve decision-making regarding quantitative and qualitative aspects of treatment.

Although members of monozygotic (MZ) twin pairs are identical in genomic sequence, epigenetic mechanisms may occasion difference in gene expression and, consequently, twin discordance in complex traits. Recent work suggests that the epigenetic process of X-inactivation in female individuals may impact on intelligence and child behavioral problems. The timing of X-inactivation has been linked to chorionic splitting in MZ twins. Dichorionic monozygotic (DC-MZ) twinning, unlike monochorionic monozygotic (MC-MZ) twinning, occurs prior to the time of X-inactivation in female organisms. Therefore, the hypothesis of a causal role of X-inactivation in intelligence and behavioral problems can be analyzed by modeling the statistical interaction between sex and chorion type for within-pair differences in these traits in MZ twins. In this study, the effect of X-inactivation on childhood behavioral problems, measured with the CBCL, was studied in a sample of 324 MZ twin pairs from the EFPTS and the effect of X-inactivation on IQ was studied in a sample of 272 twin pairs from the same twin survey. Information on chorion type, gestational age, and birth weight was additionally collated. No significant statistical interaction was found between sex and chorion type, indicating that X-inactivation is not likely involved in variations in intelligence or behavioral problems in middle childhood. Further studies are required to replicate these findings and may explore the role of X-inactivation at different ages or at the extreme scores in the spectrum of intelligence and behavioral problems or may focus on other epigenetic mechanisms.

The patient population of borderline personality disorder (BPD) is heterogeneous; many different combinations of BPD symptoms can lead to a BPD diagnosis. We investigated to what extent the covariance among four main components of BPD is explained by shared genetic and environmental factors. Using an extended twin design, multivariate genetic models were applied to the scales of the PAI-BOR, a self-report questionnaire tapping four main features of BPD (affective instability, identity problems, negative relationships, and self-harm). Data on the four BPD scales were available for 5,533 twins and 1,202 siblings from the Netherlands, Belgium, and Australia. The correlations among the scales ranged from 0.23 to 0.50 and were best explained by a genetic common pathway model. This model specifies that genes and environment influence the covariance between four main features of BPD in qualitatively similar ways, through a single latent factor representing the BPD construct. The heritability of the latent BPD factor was 51% and the remainder of its variance was explained by unique environmental influences. For each BPD scale, except self-harm, around 50% of its variance was explained by the latent BPD factor. The remaining variance for each of the four scales was explained by genetic (4% for affective instability to 20% for self-harm) and environmental (38% for negative relationships to 67% for self-harm) factors that were specific to each scale. © 2010 The Guilford Press.

Objective: This study assessed the relationship between stress reactivity (trait 1) and psychosis (trait 2) across genetically related persons (cross-twin, cross-trait design) to examine whether stress reactivity is an uncontaminated and unconfounded familial marker of psychosis risk. Method: Reactivity to stress and subclinical psychotic experiences were assessed in 289 female, general population twin-pairs. Cross-trait, within-twin associations investigating the association between stress reactivity and subclinical psychotic experiences in each person, were calculated. In addition, cross-trait, cross-twin associations were calculated to assess whether stress reactivity in one twin was moderated by subclinical psychotic experiences in the co-twin. Results: Cross-trait, within-twin analyses showed significant associations between stress reactivity and subclinical psychotic experiences in each person. In addition, the cross-trait cross-twin analyses showed that stress reactivity in twin 1 was significantly moderated by subclinical experiences in the co-twin. Conclusion: The results suggest that the psychosis phenotype cosegregates with increased emotional reactivity to stress in daily life.

Objective Evidence of a genetic basis of metabolic risk factors (MRFs) is growing. Studies examining the genetic and environmental basis of the clustering of MRFs, grouped together in the metabolic syndrome (MetS), are however sparse. The aim of this study therefore was to study the heritabilities of the MRFs and the genetic and environmental correlations between the MRFs. Methods Study participants were 768 Caucasian twins coming from 418 pairs (18–34 years). MRFs were those included in the National Cholesterol Education Program Adult Treatment Panel III definition of the MetS. Multivariate path analysis on the continuous MRFs of the MetS was implemented. Results Heritabilities ranged between 47.0% and 80.2% (men) and 58.5% and 77.9% (women) for the individual MRFs. Evidence was found for overarching genetic (A) and environmental (E) sources of variance, both however loading mainly on waist circumference. Furthermore, the model included a ‘lipids’ and a ‘blood pressure’-factor both in part attributable to A and E. The majority of the variance however was MRF-specific. Conclusion Based on our sample of young adults with a low prevalence of the MetS, it can be concluded that both genes and environment contribute significantly to the clustering of the MRFs although the majority of the variation is MRF-specific. Therefore, future QTL searches in young adults may want to focus on MRF-specific loci, rather than ‘cluster-phenotypes’ such as the MetS.

To examine, using a cross-twin cross-trait design, the hypotheses 1) that the genetic and environmental susceptibility to depression is expressed, in part, as alterations in cortisol day curves and 2) that cortisol abnormalities are not merely the consequence of depressive states or the stressors associated with its onset. Alteration of diurnal secretion of cortisol is a possible endophenotype of depression, as depressed patients show alterations in cortisol dynamics over the day.Salivary cortisol measurements were obtained in a sample of 279 twin pairs at 10 random times a day for 5 days. A structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) axis I mood disorder (SCID) was administered. Using multilevel regression analysis, the moderating influence of a lifetime diagnosis of depression in the co-twin on the association between time of day and cortisol concentrations in the proband twin was examined.Diurnal variation in cortisol in the proband twin differed as a function of lifetime diagnosis of depression in the co-twin. In addition, this moderating effect was significantly stronger for dizygotic than for monozygotic twins.Probands of co-twins with lifetime depression have a different diurnal cortisol profile than those without, suggesting that altered hypothalamic-pituitary-adrenal axis functioning is an indicator of depression susceptibility.

SummaryBackgroundMost of our knowledge about borderline personality disorder features has been obtained through the study of clinical samples. Although these studies are important in their own right, they are limited in their ability to address certain important epidemiological and aetiological questions such as the degree to which there is a genetic influence on the manifestation of borderline personality disorder features. Though family history studies of borderline personality disorder indicate genetic influences, there have been very few twin studies and the degree of genetic influence on borderline personality disorder remains unclear.MethodData were drawn from twin samples from The Netherlands (n=3918), Belgium (n=904) and Australia (n=674). In total, data were available on 5496 twins between the ages of 18 and 86 years from 3644 families who participated in the study by completion of a mailed self-report questionnaire on borderline personality disorder features.ResultsIn all countries, females scored higher than males and there was a general tendency for younger adults to endorse more borderline personality disorder features than older adults. Model-fitting results showed that additive genetic influences explain 42% of the variation in borderline personality disorder features in both men and women and that this heritability estimate is similar across The Netherlands, Belgium and Australia. Unique environmental influences explain the remaining 58% of the variance.ConclusionGenetic factors play a role in individual differences in borderline personality disorder features in Western society.

Kaufman et al. [2006] reported a higher order interaction effect between specific genetic and environmental factors in a model of depressive symptoms, requiring independent replication. BDNF Val66Met and 5-HTTLPR genotypes were determined in female participants pertaining to a large ongoing twin study. Participants also filled in questionnaires on childhood adversity and depressive symptoms. Two- and three-way interactions between genetic polymorphisms and early adversity were examined in models of depressive symptoms. BDNF Met allele(s) moderated the effect of early adversity on depressive symptoms (two-way interaction), and this BDNF Met × childhood adversity interaction in turn was moderated by 5-HTTLPR genotype (three-way interaction). However, a main effect of BDNF Met on childhood adversity was also observed, possibly indicating confounding by gene–environment correlation. Higher order interaction effects involving BDNF Val66Met, 5-HTTLPR and childhood adversity may contribute to the etiology of depressive illness. © 2007 Wiley-Liss, Inc.

Aims/hypothesis We determined the genetic contribution of 18 anthropometric and metabolic risk factors of type 2 diabetes using a young healthy twin population. Methods Traits were measured in 240 monozygotic (MZ) and 138 dizygotic (DZ) twin pairs aged 18 to 34 years. Twins were recruited from the Belgian population-based East Flanders Prospective Twin Survey, which is characterised by its accurate zygosity determination and extensive collection of perinatal and placental data, including information on chorionicity. Heritability was estimated using structural equation modelling implemented in the Mx software package. Results Intra-pair correlations of the anthropometric and metabolic characteristics did not differ between MZ monochorionic and MZ dichorionic pairs; consequently heritabilities were estimated using the classical twin approach. For body mass, BMI and fat mass, quantitative sex differences were observed; genetic variance explained 84, 85 and 81% of the total variation in men and 74, 75 and 70% in women, respectively. Heritability estimates of the waist-to-hip ratio, sum of four skinfold thicknesses and lean body mass were 70, 74 and 81%, respectively. The heritability estimates of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance and beta cell function, as well as insulin-like growth factor binding protein-1 levels were 67, 49, 48, 62 and 47%, in that order. Finally, for total cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol:HDL-cholesterol ratio, triacylglycerol, NEFA and leptin levels, genetic factors explained 75, 78, 76, 79, 58, 37 and 53% of the total variation, respectively. Conclusions/interpretation Genetic factors explain the greater part of the variation in traits related to obesity, glucose intolerance/insulin resistance and dyslipidaemia. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0784-z) contains supplementary material, which is available to authorised users.

Objective: Genetic and environmental influences on variation in distress associated with subclinical psychotic experiences were examined. Method: A total of 289 twin pairs filled in the Community Assessment of Psychic Experiences, a self-report instrument assessing subclinical positive and negative psychotic experiences and associated distress (distresspos and distressneg). Using structural equation modelling, univariate and bivariate models were fitted. Results: Univariate model fitting showed genetic and non-shared environmental influences on both distresspos and distressneg. Bivariate model fitting showed that 52% of the correlation between the two phenotypes (r = 0.46) was because of shared genes and that non-shared environmental factors accounted for 48% of the correlation. Conclusion: Liability to psychosis not only refers to the development of psychosis per se, but also to the liability to develop dysfunctional emotional appraisals. The emotive component of psychosis liability involves genetic transmission of a general, non-symptom-specific distress factor that may be a target for molecular genetic research.

Influence of chorionicity on the heritability estimates of blood pressure: a study in twins.Fagard RH, Loos RJ, Beunen G, Derom C, Vlietinck R.Hypertension and Cardiovascular Rehabilitation Unit, Faculty of Medicine, University of Leuven, KU Leuven, Belgium. robert.fagard@uz.kuleuven.ac.beBACKGROUND: A basic assumption of the twin design is that environmental influences including prenatal experiences are equal across twin types. However, the intra-uterine environment may differ according to the chorionicity of the monozygotic twins, which may have biased previous heritability estimates of blood pressure. OBJECTIVE: The aim of the present study was to assess whether the heritability of blood pressure, derived from measurements in monozygotic and dizygotic twins, differs according to the chorionicity of the monozygotic twins. METHODS: Conventional and 24-h ambulatory blood pressures were measured in 125 dizygotic twin pairs and in 97 dichorionic and 128 monochorionic monozygotic twin pairs at the age of 18-34 years. The twin sample was drawn from the East Flanders Prospective Twin Survey, in which perinatal data were collected at birth. Intra-pair correlation coefficients were calculated and compared between both types of monozygotic twin pairs. Heritability was estimated from model-fitting and path analysis, based on the dizygotic twins and, respectively, all monozygotic twins and the two subtypes. RESULTS: Intra-pair correlation coefficients for the various blood pressures, after adjustment for body mass index, ranged from 0.45 to 0.71 in the monozygotic twin pairs and did not differ significantly according to chorionicity. Heritability estimates of blood pressure were between 52 and 64%, and were similar when calculated from dizygotic twins and, respectively, dichorionic and monochorionic monozygotic twins. CONCLUSIONS: Heritability estimates of conventional and ambulatory blood pressure do not differ significantly according to the chorionicity of the monozygotic twins.

Previous work has examined the structure of subclinical positive psychotic experiences. The current study, using confirmatory factor analysis in a general population sample of young adult females, replicated a five-dimensional model, which showed excellent model fit. The results suggest stability of the five-dimensional model across adolescent and young adult life.

Previous work has demonstrated associations between lower cognitive ability and childhood and adult non-psychotic psychopathology. As both cognitive ability (CA) and child psychopathology (CP) are influenced by genetic factors, one explanation for the association is that they are the pleiotropic manifestations of the same underlying genetic factors. The present paper examines three possible causes of the association: additive genetic factors, common environmental factors and individual-specific environmental factors. Three hundred and seventy-six twin pairs from the East Flanders Prospective Twin Survey were examined with the Child Behaviour Checklist and the Wechsler Intelligence Scale for Children-Revised. The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen, based on likelihood and parsimony. The observed phenotypic correlation between CP and CA was -0.19 (95% CI: -0.09, -0.27), with genetic factors accounting for about 84% of the observed correlation. Bivariate model fitting quantified the genetic correlation between CP and CA at -0.27 (95% CI: -0.12, -0.42) and the individual-specific environmental correlation at -0.17 (95% CI: -0.03, -0.31). In children, three different genetic factors may exist: one that solely affects the liability to CP, one that has only an effect on CA and one that influences both CP and CA. While individual-specific environmental factors can influence the liability to both traits, our results suggest that most of the environmental factors that increase the risk of CP do not influence CA and vice versa.