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1. Quantitative trait locus mapping in placenta: A comparative study of chorionic villus and birth placenta

Author

Linda Dieckmann, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Katri Räikkönen, Elisabeth B. Binder, and Darina Czamara

Subjects
CVS, placenta, PheWAS, QTL, molecular trait, Genetics, QH426-470
Abstract

Summary: The placenta, a pivotal player in the prenatal environment, holds crucial insights into early developmental pathways and future health outcomes. In this study, we explored genetic molecular regulation in chorionic villus samples (CVS) from the first trimester and placenta tissue at birth. We assessed quantitative trait locus (QTL) mapping on DNA methylation and gene expression data in a Finnish cohort of 574 individuals. We found more QTLs in birth placenta than in first-trimester placenta. Nevertheless, a substantial amount of associations overlapped in their effects and showed consistent direction in both tissues, with increasing molecular genetic effects from early pregnancy to birth placenta. The identified QTLs in birth placenta were most enriched in genes with placenta-specific expression. Conducting a phenome-wide-association study (PheWAS) on the associated SNPs, we observed numerous overlaps with genome-wide association study (GWAS) hits (spanning 57 distinct traits and 23 SNPs), with notable enrichments for immunological, skeletal, and respiratory traits. The QTL-SNP rs1737028 (chr6:29737993) presented with the highest number of GWAS hits. This SNP was related to HLA-G expression via DNA methylation and was associated with various immune, respiratory, and psychiatric traits. Our findings implicate increasing genetic molecular regulation during the course of pregnancy and support the involvement of placenta gene regulation, particularly in immunological traits. This study presents a framework for understanding placenta-specific gene regulation during pregnancy and its connection to health-related traits.

Published
2024
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2. Maternal psychological distress and temperament traits in children from infancy to late childhood

Author

Marius Lahti‐Pulkkinen, Anna Lähdepuro, Jari Lahti, Polina Girchenko, Riikka Pyhälä, Rebecca M. Reynolds, Pia M. Villa, Hannele Laivuori, Eero Kajantie, Kati Heinonen, and Katri Räikkönen

Subjects
anxiety, depression, prenatal, stress, temperament, Pediatrics, RJ1-570, Psychiatry, RC435-571
Abstract

Abstract Background Maternal psychological distress during pregnancy is associated with infant temperament. Whether associations persist into late childhood, whether maternal distress is associated with temperament change from infancy to late childhood, whether associations are independent of maternal concurrent distress, and whether maternal distress has sensitive exposure periods on child temperament remain unclear. Methods Our study includes mother‐child dyads from Finnish, prospective Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. The mothers completed the Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory and Perceived Stress Scale: biweekly up to 14 times during pregnancy; once in infancy (at child age 4–12 months); and once in late childhood (at child age 7–11 years). They also completed the Infant Behavior Questionnaire Revised at the infancy (n = 2538) and Temperament in Middle Childhood Questionnaire at the late childhood (n = 2004; 1693 children had data at both follow‐ups) follow‐up on child negative affectivity, extraversion and effortful control. We examined the associations of maternal distress with child temperament with linear regression, linear mixed and Bayesian relevant lifecourse exposure models. Results Maternal distress during pregnancy was associated with higher negative affectivity and lower effortful control in children in infancy and late childhood. Maternal distress during pregnancy was also associated with increases in negative affectivity, decreases in effortful Control, and smaller decreases in extraversion from infancy to late childhood. The associations with late childhood temperament and temperament change were independent of maternal concurrent distress. Late childhood was a sensitive period for lifetime‐to‐date effects of maternal distress on late childhood negative affectivity and effortful control. Distress during pregnancy and infancy had smaller contributions. Conclusions Maternal psychological distress during pregnancy is associated with individual differences and change in child temperament from infancy to late childhood. However, distress during pregnancy has a smaller effect on late childhood temperament than maternal concurrent distress.

Published
2024
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3. Associations of polymetabolic risk of high maternal pre-pregnancy body mass index with pregnancy complications, birth outcomes, and early childhood neurodevelopment: findings from two pregnancy cohorts

Author

Polina Girchenko, Marius Lahti-Pulkkinen, Esa Hämäläinen, Hannele Laivuori, Pia M. Villa, Eero Kajantie, and Katri Räikkönen

Subjects
Pre-pregnancy BMI, BMI-defined metabolome, High BMI-related polymetabolic risk score, Pregnancy complications, Birth outcomes, Childhood neurodevelopment, Gynecology and obstetrics, RG1-991
Abstract

Abstract Background A substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(

Published
2024
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4. Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort studyResearch in context

Author

Weiyao Yin, Anna Pulakka, Abraham Reichenberg, Alexander Kolevzon, Jonas F. Ludvigsson, Kari Risnes, Marius Lahti-Pulkkinen, Martina Persson, Michael E. Silverman, Ulrika Åden, Eero Kajantie, and Sven Sandin

Subjects
Autism, Mental illness, Family risk, Cohort, Epidemiology, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. Methods: We included all children born in Sweden and Finland 1997–2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Findings: Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR = 2.02, 95% CI = 1.92–2.12; Finland: aHR = 1.63, 95% CI = 1.50–1.77), mothers (Sweden: aHR = 2.34, 95% CI = 2.24–2.43; Finland aHR = 2.12, 95% CI = 1.92–2.28), or both parents (Sweden: aHR = 3.76, 95% CI = 3.48–4.07; Finland aHR = 3.61, 95% CI = 3.20–4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or ≥three different diagnostic categories compared to no diagnosis, in fathers aHR = 1.81, 2.07, 2.52; in mothers aHR = 2.05, 2.63, 3.57). Interpretation: Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Funding: Swedish-Research-Council-2021-0214.

Published
2024
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5. Maternal postpartum depressive symptoms partially mediate the association between preterm birth and mental and behavioral disorders in children

Author

Polina Girchenko, Rachel Robinson, Ville Juhani Rantalainen, Marius Lahti-Pulkkinen, Kati Heinonen-Tuomaala, Sakari Lemola, Dieter Wolke, Daniel Schnitzlein, Esa Hämäläinen, Hannele Laivuori, Pia M. Villa, Eero Kajantie, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

Abstract Preterm birth has been linked with postpartum depressive (PPD) disorders and high symptom levels, but evidence remains conflicting and limited in quality. It remains unclear whether PPD symptoms of mothers with preterm babies were already elevated before childbirth, and whether PPD symptoms mediate/aggravate the effect of preterm birth on child mental disorders. We examined whether preterm birth associated with maternal PPD symptoms, depressive symptoms trajectories from antenatal to postpartum stage, and whether PPD symptoms mediated/aggravated associations between preterm birth and child mental disorders. Mothers of preterm (n = 125) and term-born (n = 3033) children of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study reported depressive symptoms four times within 8 weeks before and twice within 12 months after childbirth. Child mental and behavioral disorder diagnoses until age 8.4–12.8 years came from medical register. Preterm birth associated with higher PPD symptoms (mean difference = 0.19 SD, 95% CI 0.01, 0.37, p = 0.04), and higher odds (odds ratio = 2.23, 95% CI 1.22, 4.09, p = 0.009) of the mother to belong to a group that had consistently high depressive symptoms levels trajectory from antenatal to postpartum stage. PPD symptoms partially mediated and aggravated the association between preterm birth and child mental disorders. Preterm birth, maternal PPD symptoms and child mental disorders are associated, calling for timely prevention interventions.

Published
2022
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6. Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids

Author

Emily M. Frier, Chun Lin, Rebecca M. Reynolds, Karel Allegaert, Jasper V. Been, Abigail Fraser, Mika Gissler, Kristjana Einarsdóttir, Lani Florian, Bo Jacobsson, Joshua P. Vogel, Helga Zoega, Sohinee Bhattacharya, Eyal Krispin, Lars Henning Pedersen, Devender Roberts, Stefan Kuhle, John Fahey, Ben W. Mol, David Burgner, Ewoud Schuit, Aziz Sheikh, Rachael Wood, Cynthia Gyamfi-Bannerman, Jessica E. Miller, Kate Duhig, Marius Lahti-Pulkkinen, Eran Hadar, John Wright, Sarah R. Murray, and Sarah J. Stock

Subjects
Medicine, Science
Abstract

Background Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the “therapeutic window” and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. Methods The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. Results and discussion The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks’ gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.

Published
2023

7. Memory decline in young stroke survivors during a 9-year follow-up: A cohort study

Author

Siiri Laari, Katri Turunen, Tatu Kauranen, Satu Mustanoja, Marius Lahti-Pulkkinen, Turgut Tatlisumak, and Erja Poutiainen

Subjects
memory decline, young stroke survivor, ischemic stroke, long-term cognitive outcome, cognitive impairment, follow-up, Neurology. Diseases of the nervous system, RC346-429
Abstract

IntroductionA decade after stroke, young stroke survivors continue to suffer from cognitive impairment. However, it is not known whether this long-term cognitive outcome is caused in part by further cognitive decline or solely by incomplete recovery from the acute effects of ischemic stroke. We studied changes in three cognitive domains over a 9-year follow-up period after first-ever and only ischemic stroke.Patients and methodsIn this prospective, two-center cohort study, we recruited consecutive 18–65 year-old patients with acute stroke between 2007 and 2009, along with demographically matched stroke-free controls. We performed comprehensive neuropsychological assessments at 3 months, 2, and 9 years after stroke, and we also performed neurological examinations at the time of inclusion and at the 9-year follow-up. We assessed the associations among stroke, follow-up time and long-term cognitive outcomes using repeated-measures analysis of variance.ResultsThe subjects comprised 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at inclusion), along with 31 stroke-free demographic controls. We compared the cognitive changes in patients to those in controls over a 9-year follow-up. After initial recovery between 3 months and 2 years after stroke, patients showed a decline in memory between 2 and 9 years after stroke compared to controls within the same time interval (immediate recall p < 0.001; delayed recall p < 0.001; list learning p < 0.001). Other than memory, we found no difference in cognitive changes between poststroke patients and controls.DiscussionOur main finding was memory decline over a decade in young first-ever stroke patients with no further stroke or neurodegenerative disease. Our study extends the previous results of further memory decline in elderly stroke survivors to young stroke survivors.ConclusionYoung stroke survivors might be at risk of memory decline over the decade following the stroke.

Published
2022
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8. Maternal body mass index in pregnancy and mental disorders in adult offspring: a record linkage study in Aberdeen, Scotland

Author

Marius Lahti-Pulkkinen, Katri Räikkönen, Sohinee Bhattacharya, and Rebecca M. Reynolds

Subjects
Medicine, Science
Abstract

Abstract Maternal obesity in pregnancy predicts offspring psychopathology risk in childhood but it remains unclear whether maternal obesity or underweight associate with adult offspring mental disorders. We examined longitudinally whether maternal body mass index (BMI) in pregnancy predicted mental disorders in her offspring and whether the associations differed by offspring birth year among 68,571 mother–child dyads of Aberdeen Maternity and Neonatal Databank, Scotland. The offspring were born 1950–1999. Maternal BMI was measured at a mean 15.7 gestational weeks and classified into underweight, normal weight, overweight, moderate obesity and severe obesity. Mental disorders were identified from nationwide registers carrying diagnoses of all hospitalizations and deaths in Scotland in 1996–2017. We found that maternal BMI in pregnancy was associated with offspring mental disorders in a time-dependent manner: In offspring born 1950–1974, maternal underweight predicted an increased hazard of mental disorders [Hazard Ratio (HR) = 1.74; 95% Confidence Interval (CI) = 1.01–3.00)]. In offspring born 1975–1999, maternal severe obesity predicted increased hazards of any mental (HR 1.60; 95% CI 1.08–2.38) substance use (HR 1.91; 95% CI 1.03–3.57) and schizophrenia spectrum (HR 2.80; 95% CI 1.40–5.63) disorders. Our findings of time-specific associations between maternal prenatal BMI and adult offspring mental disorders may carry important public health implications by underlining possible lifelong effects of maternal BMI on offspring psychopathology.

Published
2021
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9. Cohort profile: InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland: study design and baseline characteristics

Author

Katri Räikkönen, Elisabeth Binder, Eero Kajantie, Hannele Laivuori, Rebecca Reynolds, Darina Czamara, Tuomas Kvist, Sara Sammallahti, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Linda Dieckmann, Alina Tontsch, Simone Röh, Monika Rex-Haffner, Eiina Wolford, Johan Eriksson, Sanna Suomalainen-König, and Eija Lahdensuo

Subjects
Medicine
Published
2022
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10. A genome-wide association study of total child psychiatric problems scores

Author

Alexander Neumann, Ilja M. Nolte, Irene Pappa, Tarunveer S. Ahluwalia, Erik Pettersson, Alina Rodriguez, Andrew Whitehouse, Catharina E. M. van Beijsterveldt, Beben Benyamin, Anke R. Hammerschlag, Quinta Helmer, Ville Karhunen, Eva Krapohl, Yi Lu, Peter J. van der Most, Teemu Palviainen, Beate St Pourcain, Ilkka Seppälä, Anna Suarez, Natalia Vilor-Tejedor, Carla M. T. Tiesler, Carol Wang, Amanda Wills, Ang Zhou, Silvia Alemany, Hans Bisgaard, Klaus Bønnelykke, Gareth E. Davies, Christian Hakulinen, Anjali K. Henders, Elina Hyppönen, Jakob Stokholm, Meike Bartels, Jouke-Jan Hottenga, Joachim Heinrich, John Hewitt, Liisa Keltikangas-Järvinen, Tellervo Korhonen, Jaakko Kaprio, Jari Lahti, Marius Lahti-Pulkkinen, Terho Lehtimäki, Christel M. Middeldorp, Jackob M. Najman, Craig Pennell, Chris Power, Albertine J. Oldehinkel, Robert Plomin, Katri Räikkönen, Olli T. Raitakari, Kaili Rimfeld, Lærke Sass, Harold Snieder, Marie Standl, Jordi Sunyer, Gail M. Williams, Marian J. Bakermans-Kranenburg, Dorret I. Boomsma, Marinus H. van IJzendoorn, Catharina A. Hartman, and Henning Tiemeier

Subjects
Medicine, Science
Abstract

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Published
2022

11. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author

Darina Czamara, Gökçen Eraslan, Christian M. Page, Jari Lahti, Marius Lahti-Pulkkinen, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Wenche Nystad, Siri E. Håberg, Stephanie J. London, Kieran J. O’Donnell, Elika Garg, Michael J. Meaney, Sonja Entringer, Pathik D. Wadhwa, Claudia Buss, Meaghan J. Jones, David T. S. Lin, Julie L. MacIsaac, Michael S. Kobor, Nastassja Koen, Heather J. Zar, Karestan C. Koenen, Shareefa Dalvie, Dan J. Stein, Ivan Kondofersky, Nikola S. Müller, Fabian J. Theis, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Katri Räikkönen, and Elisabeth B. Binder

Subjects
Science
Abstract

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Published
2019
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12. Optimism in adults born preterm: Systematic review and individual-participant-data meta-analysis

Author

Rachel K. Robinson, Kati Heinonen, Polina Girchenko, Marius Lahti-Pulkkinen, Eero Kajantie, Petteri Hovi, Aulikki Lano, Sture Andersson, Johan G. Eriksson, Dieter Wolke, Sakari Lemola, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

Aim Preterm birth(Methods We systematically searched PubMed and Web of Science for cohort or case-control studies(born ≥ 1970) with data on gestational age and optimism/pessimism reported using the Life-Orientation-Test-Revised in adulthood(≥18 years). The three identified studies(Helsinki Study of Very Low Birth Weight Adults; Arvo Ylppö Longitudinal Study; Avon Longitudinal Study of Parents and Children) provided data for the two-step random-effects linear regression Individual-Participant-Data meta-analysis. Results Preterm and term borns did not differ on optimism(p = 0.76). Preterms scored higher on pessimism than term borns(Mean difference = 0.35, 95%Confidence Interval 0.36, 0.60, p = 0.007), although not after full adjustment. Preterm born participants, but not term born participants, with higher birth weight z-score, had higher optimism scores (0.30 raw score units per standard deviation increase, 95% CI 0.10, 0.49, p = 0.003); preterm vs term x birth weight z-score interaction p = 0.004). Conclusions Preterm and term born adults display similar optimism. In preterms, higher birth weight may foster developmental trajectories promoting more optimistic life orientations.

Published
2021

13. A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

Author

Anna Suarez, Jari Lahti, Marius Lahti-Pulkkinen, Polina Girchenko, Darina Czamara, Janine Arloth, Anni LK. Malmberg, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Nadine Provençal, Elisabeth B. Binder, and Katri Räikkönen

Subjects
Cord blood methylation, Glucocorticoids, Polyepigenetic biomarker, Childhood mental health, Prenatal psychopathology, Prospective study, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429, Neurophysiology and neuropsychology, QP351-495
Abstract

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes. Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583). Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p

Published
2020
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14. The epigenetic clock and pubertal, neuroendocrine, psychiatric, and cognitive outcomes in adolescents

Author

Anna Suarez, Jari Lahti, Darina Czamara, Marius Lahti-Pulkkinen, Polina Girchenko, Sture Andersson, Timo E. Strandberg, Rebecca M. Reynolds, Eero Kajantie, Elisabeth B. Binder, and Katri Raikkonen

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Background Molecular aging biomarkers, such as epigenetic age predictors, predict risk factors of premature aging, and morbidity/mortality more accurately than chronological age in middle-aged and elderly populations. Yet, it remains elusive if such biomarkers are associated with aging-related outcomes earlier in life when individuals begin to diverge in aging trajectories. We tested if the Horvath epigenetic age predictor is associated with pubertal, neuroendocrine, psychiatric, and cognitive aging-related outcomes in a sample of 239 adolescents, 11.0–13.2 years-old. Results Each year increase in epigenetic age acceleration (AA) was associated with 0.06 SD units higher weight-for-age, 0.08 SD units taller height-for-age, -0.09 SD units less missed from the expected adult height, 13 and 16% higher odds, respectively, for each stage increase in breast/genitals development on the Tanner Staging Questionnaire and pubertal stage on the Pubertal Development Scale, 4.2% higher salivary cortisol upon awakening, and 18 to 34% higher odds for internalizing and thought problems on the Child Behavior Checklist (p values

Published
2018
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15. Predictors of surgical site skin infection and clinical outcome at caesarean section in the very severely obese: A retrospective cohort study.

Author

Michael Dias, Allyn Dick, Rebecca M Reynolds, Marius Lahti-Pulkkinen, and Fiona C Denison

Subjects
Medicine, Science
Abstract

IntroductionThe optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision.Material and methodsUsing a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision.ResultsLower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), pConclusionSSSI rates are high in very severely obese women following caesarean section, regardless of location of skin incision.

Published
2019
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16. Nutrition after preterm birth and adult neurocognitive outcomes.

Author

Sara Sammallahti, Eero Kajantie, Hanna-Maria Matinolli, Riikka Pyhälä, Jari Lahti, Kati Heinonen, Marius Lahti, Anu-Katriina Pesonen, Johan G Eriksson, Petteri Hovi, Anna-Liisa Järvenpää, Sture Andersson, and Katri Raikkonen

Subjects
Medicine, Science
Abstract

BACKGROUND:Preterm birth (

Published
2017
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17. Maternal depressive symptoms during and after pregnancy are associated with attention-deficit/hyperactivity disorder symptoms in their 3- to 6-year-old children.

Author

Elina Wolford, Marius Lahti, Soile Tuovinen, Jari Lahti, Jari Lipsanen, Katri Savolainen, Kati Heinonen, Esa Hämäläinen, Eero Kajantie, Anu-Katriina Pesonen, Pia M Villa, Hannele Laivuori, Rebecca M Reynolds, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

Maternal depressive symptoms during pregnancy have been associated with child behavioural symptoms of attention-deficit/hyperactivity disorder (ADHD) in early childhood. However, it remains unclear if depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain times, and if maternal depressive symptoms after pregnancy add to or mediate any prenatal effects. 1,779 mother-child dyads participated in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. Mothers filled in the Center of Epidemiological Studies Depression Scale biweekly from 12+0-13+6 to 38+0-39+6 weeks+days of gestation or delivery, and the Beck Depression Inventory-II and the Conners' Hyperactivity Index at the child's age of 3 to 6 years (mean 3.8 years, standard deviation [SD] 0.5). Maternal depressive symptoms were highly stable throughout pregnancy, and children of mothers with consistently high depressive symptoms showed higher average levels (mean difference = 0.46 SD units, 95% Confidence Interval [CI] 0.36, 0.56, p < 0.001 compared to the low group), and proportion (32.1% vs. 14.7%) and odds (odds ratio = 2.80, 95% CI 2.20, 3.57, p < 0.001) of clinically significant ADHD symptoms. These associations were not explained by the effects of maternal depressive symptoms after pregnancy, which both added to and partially mediated the prenatal effects. Maternal depressive symptoms throughout pregnancy are associated with increased ADHD symptomatology in young children. Maternal depressive symptoms after pregnancy add to, but only partially mediate, the prenatal effects. Preventive interventions suited for the pregnancy period may benefit both maternal and offspring mental health.

Published
2017
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18. Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD.

Author

Kieran J O'Donnell, Vivette Glover, Jari Lahti, Marius Lahti, Rachel D Edgar, Katri Räikkönen, and Thomas G O'Connor

Subjects
Medicine, Science
Abstract

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children's responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4-15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child's rs4680 genotype, with stronger effects obtained for the val/val (G:G) genotype relative to val/met (A:G) (all p

Published
2017
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19. Maternal Prenatal Positive Affect, Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study.

Author

Anu-Katriina Pesonen, Marius Lahti, Tiina Kuusinen, Soile Tuovinen, Pia Villa, Esa Hämäläinen, Hannele Laivuori, Eero Kajantie, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

BACKGROUND:We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation. METHODS:Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records. RESULTS:One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04-0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1-0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions. CONCLUSIONS:This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.

Published
2016
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20. Infant Growth after Preterm Birth and Mental Health in Young Adulthood.

Author

Sara Sammallahti, Marius Lahti, Riikka Pyhälä, Jari Lahti, Anu-Katriina Pesonen, Kati Heinonen, Petteri Hovi, Johan G Eriksson, Sonja Strang-Karlsson, Anna-Liisa Järvenpää, Sture Andersson, Eero Kajantie, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (< 1500 g).As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction.Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations.Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.

Published
2015
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21. Prenatal and childhood growth, and hospitalization for alcohol use disorders in adulthood: the Helsinki birth cohort study.

Author

Jari Lahti, Marius Lahti, Anu-Katriina Pesonen, Kati Heinonen, Eero Kajantie, Tom Forsén, Kristian Wahlbeck, Clive Osmond, David J P Barker, Johan G Eriksson, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

Small birth size - an indicator of a sub-optimal prenatal environment - and variation in growth after birth have been associated with non-communicable diseases in later life. We tested whether birth size or growth in childhood associated with the risk of hospital admission for alcohol use disorders (AUDs) from early to late adulthood.The sample comprised 6544 men and 6050 women born between 1934 and 1944 in Helsinki, Finland. Data on anthropometric measures were extracted from medical records and diagnoses of AUD from the Finnish Hospital Discharge Register and Causes of Death Register covering a 40-year period from 1969 to 2008.Altogether 171 women (2.8%) and 657 men (10.0%) were diagnosed at a hospital with AUD. After adjusting for major confounders, shorter length at birth, shorter height up to two years of age, and lower weight at two years associated with hospitalization for AUD in women. In men, slower growth in height, particularly from 2 to 7 years, and slower weight gain from 7 to 11 years as well as shorter height and lower weight at 7 and 11 years associated with a diagnosis of AUD in men.Pre- and postnatal growth associates with the risk for AUD later in life differently in women than in men: the fetal period and infancy seem to be the sensitive periods for women, whereas those for men the occur from toddlerhood onwards.

Published
2014
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22. Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring.

Author

Marius Lahti, Johan G Eriksson, Kati Heinonen, Eero Kajantie, Jari Lahti, Kristian Wahlbeck, Soile Tuovinen, Anu-Katriina Pesonen, Maiju Mikkonen, Clive Osmond, and Katri Räikkönen

Subjects
Medicine, Science
Abstract

BACKGROUND:Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life. METHODS:Our study sample comprised 13243 Helsinki Birth Cohort Study 1934-1944 participants (6905 men and 6338 women). According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969-2010. RESULTS:Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03), non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002), and suicide attempts (Hazard Ratio = 3.94, p = 0.01) in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01), non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02) schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02), mood disorders (Hazard Ratio = 2.40, p = 0.002), non-psychotic mood disorders (Hazard Ratio = 2.91, p

Published
2014
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23. Early life origins cognitive decline: findings in elderly men in the Helsinki Birth Cohort Study.

Author

Katri Raikkonen, Eero Kajantie, Anu-Katriina Pesonen, Kati Heinonen, Hanna Alastalo, Jukka T Leskinen, Kai Nyman, Markus Henriksson, Jari Lahti, Marius Lahti, Riikka Pyhälä, Soile Tuovinen, Clive Osmond, David J P Barker, and Johan G Eriksson

Subjects
Medicine, Science
Abstract

To examine whether the adverse effects of slow prenatal and postnatal growth on cognitive function persist to old age and predict age related cognitive decline.A longitudinal birth cohort study of men born in Helsinki, Finland 1934-44.Nine-hundred-thirty-one men of the Helsinki Birth Cohort Study, with detailed data on growth from birth to adulthood, aged 20.1 (SD = 1.4) at the first and 67.9 (SD = 2.5) years at the second cognitive testing.The Finnish Defense Forces Basic Intellectual Ability Test assessed twice over nearly five decades apart.Lower weight, length and head circumference at birth were associated with lower cognitive ability at 67.9 years (1.04-1.55 points lower ability per each standard deviation [SD] unit decrease in body size, 95% Confidence Interval [95%CI]: 0.05 to 2.72) and with cognitive decline after 20.1 years (0.07-0.11 SD decline over time per each SD decrease in body size, 95%CI:0.00 to 0.19). Men who were born larger were more likely to perform better in the cognitive ability test over time (1.22-1.43 increase in odds to remain in the top relative to the lower two thirds in ability over time per each SD increase in body size, 95%CI:1.04 to 1.79) and were more resilient to cognitive decline after 20.1 years (0.69 to 0.76 decrease in odds to decline from than remain in the top third of ability over time per each SD increase in body size, 95%CI:0.49 to 0.99). Slower growth between birth and two years in weight, height and body mass index was associated with lower cognitive ability at 67.9 years, but not with cognitive decline.Poorer lifetime cognitive ability is predicted by slower growth before and after birth. In predicting resilience to age related cognitive decline, the period before birth seems to be more critical.

Published
2013
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24. Personality and dietary intake - findings in the Helsinki birth cohort study.

Author

Anna-Maija K Tiainen, Satu Männistö, Marius Lahti, Paul A Blomstedt, Jari Lahti, Mia-Maria Perälä, Katri Räikkönen, Eero Kajantie, and Johan G Eriksson

Subjects
Medicine, Science
Abstract

Personality traits are associated with health outcomes including non-communicable diseases. This could be partly explained by lifestyle related factors including diet. The personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness are linked with resilience, meaning adaptability in challenging situations. Resilient people usually comply with favorable health behaviors.Our objective was to explore the associations between food and nutrient intake, personality traits and resilience.A validated semi-quantitative food frequency questionnaire was used to measure diet and the NEO-personality inventory to assess personality in 1681 subjects. Linear regression analysis was used to explore diet-personality associations and cluster analysis to define resilient and non-resilient personality profiles.Adjusting for age, education and energy intake, and applying Bonferroni corrections, openness in men was associated with higher vegetable (14.9 g/d for 1 SD increase in the personality score, PBonf

Published
2013
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25. Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Author

Polina Girchenko, Marius Lahti-Pulkkinen, Jari Lipsanen, Kati Heinonen, Jari Lahti, Ville Rantalainen, Esa Hämäläinen, Hannele Laivuori, Pia M. Villa, Eero Kajantie, Katri Räikkönen, Department of Psychology and Logopedics, Developmental Psychology Research Group, Teachers' Academy, Medicum, HUSLAB, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Clinicum, HUS Gynecology and Obstetrics, Children's Hospital, Lastentautien yksikkö, HUS Children and Adolescents, Tampere University, Welfare Sciences, Clinical Medicine, and Department of Gynaecology and Obstetrics

Subjects
Risk, Mothers, PROFILE, 3124 Neurology and psychiatry, Body Mass Index, SUPPLEMENTATION, DIET, Cellular and Molecular Neuroscience, INFLAMMATION, 3123 Gynaecology and paediatrics, Pregnancy, Humans, OXIDATIVE STRESS, AUTISM, Child, Molecular Biology, OUTCOMES, Mental Disorders, 3112 Neurosciences, RISKS, Psychiatry and Mental health, OBESITY, 1182 Biochemistry, cell and molecular biology, Female, HEALTH, 3111 Biomedicine
Abstract

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4–12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7–65.6%, and hence the predictive significance of the model, and mediated 60.8–75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

Published
2022
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26. Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing

Author

Darina Czamara, Cristiana Cruceanu, Marius Lahti-Pulkkinen, Linda Dieckmann, Maik Ködel, Susann Sauer, Monika Rex-Haffner, Sara Sammallahti, Eero Kajantie, Hannele Laivuori, Jari Lahti, Katri Räikkönen, Elisabeth B. Binder, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics

Subjects
chorionic villus sampling, DNA Copy Number Variations, placenta, Placenta, prenatal testing transcriptome sequencing, Organic Chemistry, General Medicine, Hormones, Catalysis, Computer Science Applications, Pregnancy Complications, Inorganic Chemistry, Pregnancy Trimester, First, congenital malformations, Pregnancy, 3123 Gynaecology and paediatrics, Humans, Female, Genetic Testing, Physical and Theoretical Chemistry, Child, Transcriptome, Molecular Biology, Spectroscopy
Abstract

Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth. publishedVersion

Published
2022
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27. Longitudinal Metabolic Profiling of Maternal Obesity, Gestational Diabetes, and Hypertensive Pregnancy Disorders

Author

Polina Girchenko, Marius Lahti-Pulkkinen, Esa Hämäläinen, Katri Räikkönen, Emilia Huvinen, Beata Stach-Lempinen, Johan G. Eriksson, Jemina Kivelä, Heidi Sormunen-Harju, Saila B. Koivusalo, Katja Murtoniemi, Eero Kajantie, Pia M. Villa, Rebecca M. Reynolds, Hannele Laivuori, Tampere University, Clinical Medicine, Department of Gynaecology and Obstetrics, Department of Public Health, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Department of Psychology and Logopedics, Developmental Psychology Research Group, HYKS erva, South Carelia Social and Health care District Eksote, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, University of Helsinki, Hyvinkää Hospital Area, HUSLAB, Medicum, Department of Medical and Clinical Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Pregnancy and Genes, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, and Doctoral Programme in Human Behaviour

Subjects
0301 basic medicine, Magnetic Resonance Spectroscopy, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Biochemistry, Body Mass Index, Obesity, Maternal, biomolecular, 0302 clinical medicine, Endocrinology, 3123 Gynaecology and paediatrics, Pregnancy, Longitudinal Studies, 2. Zero hunger, diabetes, Obstetrics, WOMEN, metabolomics, 3. Good health, Gestational diabetes, ACID, Metabolome, Gestation, Female, pregnancy, HEALTH, AcademicSubjects/MED00250, Adult, medicine.medical_specialty, hypertension, pre-eclampsia, Gestational Age, 030209 endocrinology & metabolism, Context (language use), 3121 Internal medicine, Preeclampsia, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Metabolomics, Obesity, Online Only Articles, Clinical Research Articles, business.industry, Biochemistry (medical), Hypertension, Pregnancy-Induced, medicine.disease, Pregnancy Complications, Diabetes, Gestational, nuclear magnetic resonance, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, gestational, business, Body mass index, pregnant women
Abstract

Context Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. Objective To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. Design, Setting and Participants A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. Main Outcome Measures We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. Results Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. Conclusions This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

Published
2021
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28. Effect of Vitamin D3 Supplementation in the First 2 Years of Life on Psychiatric Symptoms at Ages 6 to 8 Years

Author

Samuel Sandboge, Katri Räikkönen, Marius Lahti-Pulkkinen, Helena Hauta-alus, Elisa Holmlund-Suila, Polina Girchenko, Eero Kajantie, Outi Mäkitie, Sture Andersson, and Kati Heinonen

Subjects
General Medicine
Abstract

ImportanceVitamin D is associated with neurodevelopment, but causality, critical windows, and potentials for modification remain unknown.ObjectiveTo determine the impact of high-dose (1200 IU) vs standard-dose (400 IU) vitamin D3 supplementation during the first 2 years on psychiatric symptoms at ages 6 to 8 years and whether the impact is different in children with lower vs higher maternal vitamin D3 levels; lower vs higher levels were defined as 25-hydroxyvitamin D (25[OH]D) less than 30 ng/mL vs 30 ng/mL or greater.Design, Setting, and ParticipantsThis study was a long-term follow-up of the double-blind randomized clinical trial (RCT) Vitamin D Intervention in Infants (VIDI) conducted at a single center in Helsinki, Finland, at 60 degrees north latitude. Recruitment for VIDI took place in 2013 to 2014. Follow-up data for secondary data analysis were collected 2020 to 2021. VIDI originally included 987 term-born infants; 546 of these individuals participated in the follow-up at ages 6 to 8 years, among whom 346 individuals had data on parent-reported psychiatric symptoms. Data were analyzed from June 2022 to March 2023.InterventionsThere were 169 infants randomized to receive 400-IU and 177 infants randomized to receive 1200-IU oral vitamin D3 supplementation daily from ages 2 weeks to 24 months.Main Outcomes and MeasuresPrimary outcomes were internalizing, externalizing, and total problems scores, with clinically significant problems defined as T scores of 64 or greater in the Child Behavior Checklist questionnaire.ResultsAmong 346 participants (164 females [47.4%]; mean [SD] age, 7.1 [0.4] years), the vitamin D3 dose was 400 IU for 169 participants and 1200 IU for 177 participants. Clinically significant internalizing problems occurred in 10 participants in the 1200-IU group (5.6% prevalence) compared with 20 participants (11.8%) in the 400-IU group (odds ratio, 0.40; 95% CI, 0.17-0.94; P = .04) after adjustment for sex, birth season, maternal depressive symptoms at birth, and parental single status at follow-up. In a post hoc subgroup analysis, 48 children in the 400-IU group with maternal 25(OH)D concentrations less than 30 ng/mL had higher internalizing problems scores compared with children in the 1200-IU group, including 44 children with maternal 25(OH)D concentrations below 30 ng/mL (adjusted mean difference, 0.49; 95% CI, 0.09-0.89; P = .02) and 91 children with maternal concentrations above 30 ng/mL (adjusted mean difference, 0.37; 95% CI, 0.03-0.72; P = .04). Groups did not differ in externalizing or total problems.Conclusions and RelevanceThis randomized clinical trial found that higher-than-standard vitamin D3 supplementation in the first 2 years decreased risk of internalizing problems at ages 6 to 8 years.Trial RegistrationClinicalTrials.gov Identifiers: NCT01723852 (VIDI) and NCT04302987 (VIDI2)

Published
2023
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29. Maternal Psychological Resilience During Pregnancy and Newborn Telomere Length: A Prospective Study

Author

Elizabeth H. Blackburn, Eero Kajantie, Marius Lahti-Pulkkinen, Katri Räikkönen, Elissa S. Epel, Sonja Entringer, Jue Lin, Claudia Buss, Pathik D. Wadhwa, and Glenn Verner

Subjects
Maternal Health, Reproductive health and childbirth, Medical and Health Sciences, Cohort Studies, stress, 0302 clinical medicine, Pregnancy, Prospective Studies, Prospective cohort study, Pediatric, Psychiatry, Family Characteristics, telomere, Obstetrics, Telomere, Resilience, Psychological, Fetal Blood, 3. Good health, Psychiatry and Mental health, Mental Health, psychological resilience, Female, pregnancy, Adult, medicine.medical_specialty, positive psychology, Context (language use), Real-Time Polymerase Chain Reaction, Article, 03 medical and health sciences, Maternal stress, Social support, Behavioral and Social Science, medicine, Humans, Family, Resilience, business.industry, Contraception/Reproduction, Psychology and Cognitive Sciences, Infant, Newborn, Infant, Telomere Homeostasis, social support, Newborn, medicine.disease, 030227 psychiatry, Pregnancy Complications, Good Health and Well Being, fetal programming, Psychological, business, 030217 neurology & neurosurgery
Abstract

Objective: In the context of the importance of elucidating the determinants of the initial, newborn setting of telomere length (TL), it is increasingly evident that maternal stress and stress-related processes during pregnancy play a major role. Although psychological resilience may function as a buffer, research in this area has not yet examined its potential role vis-à-vis that of stress. The authors examined the relationship between maternal psychological resilience during pregnancy and newborn TL. Methods: In a sample of 656 mother-child dyads from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort, multiple serial assessments were conducted over the course of pregnancy to quantify maternal stress, negative and positive emotional responses to pregnancy events, positive affect, and perceived social support. Principal component analysis identified two latent factors: stress and positivity. A measure of resilience was computed by regressing the positivity factor on the stress factor, in order to quantify positivity after accounting for stress. TL was measured using quantitative polymerase chain reaction in leukocytes extracted from cord blood shortly after birth. Linear regression was used to predict newborn TL from maternal resilience during pregnancy, adjusting for other potential determinants. Results: Maternal stress significantly predicted shorter newborn TL (β=−0.079), and positivity significantly predicted longer TL (β=0.135). Maternal resilience (positivity accounting for stress) was significantly and positively associated with newborn TL (β=0.114, 95% CI=0.035, 0.189), with each standard deviation increase in resilience predicting 12% longer newborn TL. Conclusions: The results indicate that maternal psychological resilience may exert a salubrious effect on offspring telomere biology and highlight the importance of enhancing maternal mental health and well-being during pregnancy.

Published
2021
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30. Positive maternal mental health during pregnancy and mental and behavioral disorders in children: A prospective pregnancy cohort study

Author

Anna Lähdepuro, Marius Lahti‐Pulkkinen, Riikka Pyhälä, Soile Tuovinen, Jari Lahti, Kati Heinonen, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Eero Kajantie, Polina Girchenko, Katri Räikkönen, Tampere University, Welfare Sciences, Department of Gynaecology and Obstetrics, Clinical Medicine, Department of Psychology and Logopedics, Developmental Psychology Research Group, Medicum, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, Helsinki Institute of Life Science HiLIFE, Clinicum, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Hyvinkää Hospital Area, HUS Children and Adolescents, Lastentautien yksikkö, and Children's Hospital

Subjects
OUTCOMES, 515 Psychology, child psychiatry, prenatal well-being, NEGATIVE AFFECT, DEPRESSION, 3124 Neurology and psychiatry, Psychiatry and Mental health, PANAS, positive mental health, 3123 Gynaecology and paediatrics, Pediatrics, Perinatology and Child Health, MINDFULNESS, Developmental and Educational Psychology, ANXIETY, VALIDITY, METAANALYSIS, Positive mental health
Abstract

BackgroundThe role of positive maternal mental health during pregnancy in child mental health remains largely unknown. We investigated whether positive maternal mental health during pregnancy is associated with lower hazards of mental and behavioral disorders in children and mitigates the adverse effects of negative maternal mental health.MethodsAmong 3,378 mother–child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study, mothers reported their positive mental health biweekly throughout pregnancy with the Positive and Negative Affect Schedule, the Spielberger State Anxiety Inventory Curiosity scale, and a visual analogue scale for social support, and negative mental health with the Center for Epidemiologic Studies Depression Scale. We extracted data on their mental and behavioral disorder diagnoses from a nationwide medical register. This register provided data on their children’s mental and behavioral disorder diagnoses as well, from birth until 8.4−12.8 (Median = 10.2, Interquartile Range 9.7−10.8) years of age.ResultsA positive maternal mental health composite score during pregnancy was associated with a lower hazard of any mental and behavioral disorder among all children [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI) 0.71 − 0.87] and among children of mothers experiencing clinically relevant depressive symptoms during pregnancy [HR = 0.80, 95%CI 0.64 − 1.00] and/or mental and behavioral disorders before or during pregnancy [HR = 0.69, 95%CI 0.55−0.86]. These associations were independent of covariates.ConclusionsChildren whose mothers had more positive mental health during pregnancy were less likely to develop mental and behavioral disorders. Protective effects were seen also among children of mothers facing mental health adversities before or during pregnancy.

Published
2022
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31. A large-scale genome-wide association study meta-analysis of cannabis use disorder

Author

Emma C Johnson, Ditte Demontis, Thorgeir E Thorgeirsson, Raymond K Walters, Renato Polimanti, Alexander S Hatoum, Sandra Sanchez-Roige, Sarah E Paul, Frank R Wendt, Toni-Kim Clarke, Dongbing Lai, Gunnar W Reginsson, Hang Zhou, June He, David A A Baranger, Daniel F Gudbjartsson, Robbee Wedow, Daniel E Adkins, Amy E Adkins, Jeffry Alexander, Silviu-Alin Bacanu, Tim B Bigdeli, Joseph Boden, Sandra A Brown, Kathleen K Bucholz, Jonas Bybjerg-Grauholm, Robin P Corley, Louisa Degenhardt, Danielle M Dick, Benjamin W Domingue, Louis Fox, Alison M Goate, Scott D Gordon, Laura M Hack, Dana B Hancock, Sarah M Hartz, Ian B Hickie, David M Hougaard, Kenneth Krauter, Penelope A Lind, Jeanette N McClintick, Matthew B McQueen, Jacquelyn L Meyers, Grant W Montgomery, Ole Mors, Preben B Mortensen, Merete Nordentoft, John F Pearson, Roseann E Peterson, Maureen D Reynolds, John P Rice, Valgerdur Runarsdottir, Nancy L Saccone, Richard Sherva, Judy L Silberg, Ralph E Tarter, Thorarinn Tyrfingsson, Tamara L Wall, Bradley T Webb, Thomas Werge, Leah Wetherill, Margaret J Wright, Stephanie Zellers, Mark J Adams, Laura J Bierut, Jason D Boardman, William E Copeland, Lindsay A Farrer, Tatiana M Foroud, Nathan A Gillespie, Richard A Grucza, Kathleen Mullan Harris, Andrew C Heath, Victor Hesselbrock, John K Hewitt, Christian J Hopfer, John Horwood, William G Iacono, Eric O Johnson, Kenneth S Kendler, Martin A Kennedy, Henry R Kranzler, Pamela A F Madden, Hermine H Maes, Brion S Maher, Nicholas G Martin, Matthew McGue, Andrew M McIntosh, Sarah E Medland, Elliot C Nelson, Bernice Porjesz, Brien P Riley, Michael C Stallings, Michael M Vanyukov, Scott Vrieze, Lea K Davis, Ryan Bogdan, Joel Gelernter, Howard J Edenberg, Kari Stefansson, Anders D Børglum, Arpana Agrawal, Raymond Walters, Emma Johnson, Jeanette McClintick, Alexander Hatoum, Frank Wendt, Mark Adams, Amy Adkins, Fazil Aliev, Anthony Batzler, Sarah Bertelsen, Joanna Biernacka, Tim Bigdeli, Li-Shiun Chen, Yi-Ling Chou, Franziska Degenhardt, Anna Docherty, Alexis Edwards, Pierre Fontanillas, Jerome Foo, Josef Frank, Ina Giegling, Scott Gordon, Laura Hack, Annette Hartmann, Sarah Hartz, Stefanie Heilmann-Heimbach, Stefan Herms, Colin Hodgkinson, Per Hoffman, Jouke Hottenga, Martin Kennedy, Mervi Alanne-Kinnunen, Bettina Konte, Jari Lahti, Marius Lahti-Pulkkinen, Lannie Ligthart, Anu Loukola, Brion Maher, Hamdi Mbarek, Andrew McIntosh, Matthew McQueen, Jacquelyn Meyers, Yuri Milaneschi, Teemu Palviainen, John Pearson, Roseann Peterson, Samuli Ripatti, Euijung Ryu, Nancy Saccone, Jessica Salvatore, Melanie Schwandt, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen-Chyong Wang, Bradley Webb, Amanda Wills, Jason Boardman, Danfeng Chen, Doo-Sup Choi, William Copeland, Robert Culverhouse, Norbert Dahmen, Benjamin Domingue, Sarah Elson, Mark Frye, Wolfgang Gäbel, Caroline Hayward, Marcus Ising, Margaret Keyes, Falk Kiefer, John Kramer, Samuel Kuperman, Susanne Lucae, Michael Lynskey, Wolfgang Maier, Karl Mann, Satu Männistö, Bertram Müller-Myhsok, Alison Murray, John Nurnberger, Aarno Palotie, Ulrich Preuss, Katri Räikkönen, Maureen Reynolds, Monika Ridinger, Norbert Scherbaum, Marc Schuckit, Michael Soyka, Jens Treutlein, Stephanie Witt, Norbert Wodarz, Peter Zill, Daniel Adkins, Dorret Boomsma, Laura Bierut, Sandra Brown, Kathleen Bucholz, Sven Cichon, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Danielle Dick, Johan Eriksson, Lindsay Farrer, Tatiana Foroud, Nathan Gillespie, Alison Goate, David Goldman, Richard Grucza, Dana Hancock, Andrew Heath, John Hewitt, Christian Hopfer, William Iacono, Eric Johnson, Jaakko Kaprio, Victor Karpyak, Kenneth Kendler, Henry Kranzler, Paul Lichtenstein, Penelope Lind, Matt McGue, James MacKillop, Pamela Madden, Hermine Maes, Patrik Magnusson, Nicholas Martin, Sarah Medland, Grant Montgomery, Elliot Nelson, Markus Nöthen, Abraham Palmer, Nancy Pederson, Brenda Penninx, John Rice, Marcella Rietschel, Brien Riley, Richard Rose, Dan Rujescu, Pei-Hong Shen, Judy Silberg, Michael Stallings, Ralph Tarter, Michael Vanyukov, Tamara Wall, John Whitfield, Hongyu Zhao, Benjamin Neale, Howard Edenberg, Technology Centre, Department of Psychology and Logopedics, Developmental Psychology Research Group, University Management, HUSLAB, Genetic Epidemiology, Institute for Molecular Medicine Finland, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Faculty of Arts, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Research Programs Unit, Diabetes and Obesity Research Program, Department of General Practice and Primary Health Care, Johan Eriksson / Principal Investigator, Clinicum, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and APH - Methodology

Subjects
Risk, Marijuana Abuse, medicine.medical_specialty, Alcohol abuse, Disease, Polymorphism, Single Nucleotide, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Humans, 030212 general & internal medicine, Psychiatry, Borderline personality disorder, Biological Psychiatry, business.industry, Articles, Mental illness, medicine.disease, Mental health, 030227 psychiatry, 3. Good health, Substance abuse, Psychiatry and Mental health, Translational science, business, Genome-Wide Association Study, Psychopathology
Abstract

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Published
2020
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32. Prenatal programming of child neurocognitive abilities and maternal mental health

Author

Soile Tuovinen, Marius Lahti-Pulkkinen, Eero Kajantie, Ville Rantalainen, and Katri Räikkönen

Subjects
0301 basic medicine, Pregnancy, business.industry, Endocrinology, Diabetes and Metabolism, Clinical study design, Prenatal Programming, 030209 endocrinology & metabolism, Cognition, medicine.disease, Mental health, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Mood, medicine, Anxiety, medicine.symptom, business, Neurocognitive, Clinical psychology
Abstract

Maternal mental health problems during pregnancy, especially mood and anxiety disorders and symptoms, are common. They not only hinder maternal well-being and health during pregnancy but also are associated with physical and mental health adversities in the offspring. We provide here a review of the studies published between 2017 and 2019, which reported on the associations between maternal mental health problems during pregnancy and child neurocognitive outcomes. We identified eight studies, which reported a mixed pattern of findings. While the balance of evidence favors lack of associations, small sample sizes and heterogeneity in study designs, exposures, outcomes, and covariate adjustments between the studies preclude firm conclusions. The reviewed studies encourage further research filling in the knowledge gaps we identified.

Published
2020
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33. Cohort profile

Author

Tuomas Kvist, Sara Sammallahti, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Darina Czamara, Linda Dieckmann, Alina Tontsch, Simone Röh, Monika Rex-Haffner, Eiina Wolford, Rebecca Reynolds, Johan Eriksson, Sanna Suomalainen-König, Hannele Laivuori, Eero Kajantie, Eija Lahdensuo, Elisabeth Binder, Katri Räikkönen, Department of Psychology and Logopedics, Developmental Psychology Research Group, HUS Children and Adolescents, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Medical and Clinical Genetics, Helsinki Institute of Life Science HiLIFE, Joint Activities, Helsinki Institute of Life Science HiLIFE, Lastentautien yksikkö, Children's Hospital, Child and Adolescent Psychiatry / Psychology, Tampere University, Clinical Medicine, and Department of Gynaecology and Obstetrics

Subjects
515 Psychology, Epidemiology, Placenta, public health, 1184 Genetics, developmental biology, physiology, Infant, Newborn, General Medicine, 3142 Public health care science, environmental and occupational health, Cohort Studies, Fetal Diseases, 3123 Gynaecology and paediatrics, Pregnancy, Medicine, Humans, Female, genetics, Prospective Studies, Finland
Abstract

PurposeThe InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort.ParticipantsWe included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9+0 and 21+6 gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing.Findings to dateWe have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child’s age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data.Future plansMultiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratification and understanding of the biological mechanisms involved in prenatal programming of health and disease.

Published
2022
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34. A genome-wide association study of total child psychiatric problems scores

Author

Carol A. Wang, Erik Pettersson, Jari Lahti, Irene Pappa, Gail M. Williams, Peter J. van der Most, Olli T. Raitakari, Jackob M. Najman, Henning Tiemeier, Amanda G. Wills, Craig E. Pennell, Terho Lehtimäki, Jouke-Jan Hottenga, Katri Räikkönen, Jakob Stokholm, Tarunveer S. Ahluwalia, Eva Krapohl, Marinus H. van IJzendoorn, Ilkka Seppälä, Christian Hakulinen, John K. Hewitt, Joachim Heinrich, Catharina E. M. van Beijsterveldt, Robert Plomin, Beben Benyamin, Marius Lahti-Pulkkinen, Lærke Sass, Ville Karhunen, Meike Bartels, Beate St Pourcain, Marie Standl, Silvia Alemany, Andrew J. O. Whitehouse, Alexander Neumann, Carla M. T. Tiesler, Gareth E. Davies, Elina Hyppönen, Catharina A. Hartman, Liisa Keltikangas-Järvinen, Ilja M. Nolte, Ang Zhou, Dorret I. Boomsma, Anjali K. Henders, Alina Rodriguez, Klaus Bønnelykke, Christel M. Middeldorp, Hans Bisgaard, Anke R. Hammerschlag, Kaili Rimfeld, Albertine J. Oldehinkel, Teemu Palviainen, Chris Power, Jaakko Kaprio, Tellervo Korhonen, Marian J. Bakermans-Kranenburg, Natalia Vilor-Tejedor, Yi Lu, Quinta Helmer, Anna Suarez, Jordi Sunyer, Harold Snieder, Neumann, Alexander [0000-0001-6653-3203], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Rodriguez, Alina [0000-0003-1209-8802], van der Most, Peter J [0000-0001-8450-3518], Palviainen, Teemu [0000-0002-7847-8384], Kaprio, Jaakko [0000-0002-3716-2455], Lahti-Pulkkinen, Marius [0000-0002-5244-5525], Najman, Jackob M [0000-0001-7079-2080], Tiemeier, Henning [0000-0002-4395-1397], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Institute for Molecular Medicine Finland, Genetic Epidemiology, University of Helsinki, Developmental Psychology Research Group, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Faculty Common Matters (Faculty of Education), Psychosocial factors and health, Medicum, Tellervo Korhonen / Principal Investigator, Department of Public Health, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Clinical Child and Family Studies, LEARN! - Child rearing, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S, Benyamin, Beben, Zhou, Ang, Hyppönen, Elina, and Tiemeier, Henning

Subjects
Bipolar Disorder, Genome-wide association study, Expression, Quality-control, Genome-wide association studies, genome-wide, 0302 clinical medicine, Human genetics, 0303 health sciences, education.field_of_study, Multidisciplinary, Bipolar Disorder/genetics, 1184 Genetics, developmental biology, physiology, Single Nucleotide, Metaanalysis, Neuroticism, 3. Good health, Physical sciences, Eating disorders, psychiatric disorders, Schizophrenia, Genome-Wide Association Study/methods, Anxiety, medicine.symptom, Attention Deficit Disorder with Hyperactivity/genetics, Research Article, medicine.medical_specialty, General psychopathology factor, General Science & Technology, Genetic loci, Population, FOS: Physical sciences, Polymorphism, Single Nucleotide, Age-of-onset, Heritability, 03 medical and health sciences, children, medicine, ADHD, Humans, Genetic Predisposition to Disease, Clinical genetics, Bipolar disorder, Polymorphism, Psychiatry, education, childhood, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, business.industry, Questionnaire, Single nucleotide polymorphisms, medicine.disease, Research and analysis methods, Attention-deficit/hyperactivity disorder, Attention Deficit Disorder with Hyperactivity, Symptoms, Autism, Gene expression, Human medicine, 3111 Biomedicine, business, 030217 neurology & neurosurgery, Model, Genome-Wide Association Study
Abstract

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits. The work of H. Tiemeier is further supported by a European Union’s Horizon 2020 research and innovation program (Contract grant number: 633595, DynaHealth) and a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). https://www.nwo.nl/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2022
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35. Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies

Author

Linda Dieckmann, Cristiana Cruceanu, Marius Lahti-Pulkkinen, Jari Lahti, Tuomas Kvist, Hannele Laivuori, Sara Sammallahti, Pia M. Villa, Sanna Suomalainen-König, Rebecca C. Rancourt, Andreas Plagemann, Wolfgang Henrich, Johan G. Eriksson, Eero Kajantie, Sonja Entringer, Thorsten Braun, Katri Räikkönen, Elisabeth B. Binder, Darina Czamara, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, Department of Psychology and Logopedics, Developmental Psychology Research Group, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Children and Adolescents, Children's Hospital, Clinicum, HUS Gynecology and Obstetrics, Diabetes and Obesity Research Program, Research Programs Unit, Department of General Practice and Primary Health Care, Lastentautien yksikkö, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, SAMPLES, Placenta, Cell type estimation, SINGLE COURSE, Gestational Age, QUANTILE NORMALIZATION, DEVELOPMENTAL ORIGINS, Epigenesis, Genetic, Cellular and Molecular Neuroscience, Pre-Eclampsia, SDG 3 - Good Health and Well-being, Pregnancy, 3123 Gynaecology and paediatrics, Prenatal Diagnosis, Humans, Chorionic villi, ANTENATAL BETAMETHASONE TREATMENT, Molecular Biology, EPIGENOME-WIDE ASSOCIATION, Pharmacology, Fetal Growth Retardation, DNA methylation, Infant, Newborn, Reproducibility of Results, Cell Biology, DECONVOLUTION, EPIGENETICS, 1182 Biochemistry, cell and molecular biology, Molecular Medicine, CpG Islands, Female, Human placenta, Reference-free deconvolution, Reference-based deconvolution, PACKAGE
Abstract

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.

Published
2022

36. ADHD symptoms and diagnosis in adult preterms: systematic review, IPD meta-analysis, and register-linkage study

Author

Rachel Robinson, Polina Girchenko, Anna Pulakka, Kati Heinonen, Anna Lähdepuro, Marius Lahti-Pulkkinen, Petteri Hovi, Marjaana Tikanmäki, Peter Bartmann, Aulikki Lano, Lex W. Doyle, Peter J. Anderson, Jeanie L. Y. Cheong, Brian A. Darlow, Lianne J. Woodward, L. John Horwood, Marit S. Indredavik, Kari Anne I. Evensen, Neil Marlow, Samantha Johnson, Marina Goulart de Mendonca, Eero Kajantie, Dieter Wolke, Katri Räikkönen, Tampere University, and Welfare Sciences

Subjects
Lav fødselsvekt, Preterm fødsel, 515 Psychology, RJ, Midical sciences: 700 [VDP], Pediatrics, Perinatology and Child Health, BF, ADHD, Preterm birth, Low birth weigth, Medisinske fag: 700 [VDP], RC
Abstract

Background This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. Methods (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978–1995) examined differences in self-reported ADHD symptoms[age 18–36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987–31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. Results Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] −0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p p z-score (RR = 0.88, 95% CI 0.80, 0.97, p Conclusions While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. Impact Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born adults may not self-report increased ADHD symptoms. However, they have a higher risk of ADHD diagnosis, warranting preventive strategies and interventions to reduce the presentation of more severe ADHD symptomatology in adulthood.

Published
2022

37. Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis

Author

Hedvig Nordeng, Dawn P. Misra, Katri Räikkönen, Marleen M.H.J. van Gelder, Claudia Holzman, Kate E. Pickett, Kiran Shaikh, Dan J. Stein, Liselott Andersson, Seyi Soremekun, Faruk Uguz, Tanja G. M. Vrijkotte, Marius Lahti-Pulkkinen, Ursula Winterfeld, Birit F.P. Broekman, H.J.H. Kuijpers, Heather J. Zar, Gal Dubnov-Raz, Stephanie L. Prady, Henning Tiemeier, J. Jo Kim, Frank M.M.A. van der Heijden, Anne Laure Sutter-Dallay, Nel Roeleveld, Shahirose Premji, Maria Niemi, Pinelopi Varela, Ali S. Khashan, Dan Mason, Jaime C. Slaughter-Acey, Janet L. Peacock, Judith B. Prins, Iannis M. Zervas, Mine Sahingoz, Richelle Vlenterie, H. Ross Anderson, Monica Pop-Purceleanu, Betty R. Kirkwood, Richard K. Silver, Ema Ferreira, Emma Fransson, Christine Rubertsson, Inger Sundström-Poromaa, Hanan El Marroun, Psychiatry, APH - Mental Health, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Public and occupational health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, ARD - Amsterdam Reproduction and Development, and APH - Aging & Later Life

Subjects
Adult, medicine.medical_specialty, Birth weight, Gestational Age, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Birth Weight, Humans, 030212 general & internal medicine, Depression (differential diagnoses), Depression, business.industry, Obstetrics, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Odds ratio, Infant, Low Birth Weight, medicine.disease, Antidepressive Agents, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 030227 psychiatry, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Pregnancy Complications, Low birth weight, Meta-analysis, Infant, Small for Gestational Age, Apgar Score, Premature Birth, Small for gestational age, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Selective Serotonin Reuptake Inhibitors
Abstract

Item does not contain fulltext OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Published
2021
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38. Anti-inflammatory Potential of Maternal Diet During Pregnancy: A Promise to Promote the Mental Health of Children

Author

Marius Lahti-Pulkkinen, Katri Räikkönen, and Polina Girchenko

Subjects
medicine.medical_specialty, Pregnancy, medicine.drug_class, business.industry, MEDLINE, medicine.disease, Mental health, Anti-inflammatory, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Intensive care medicine, business, Biological Psychiatry
Published
2021
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39. Reference-Based Versus Reference-Free Cell Type Estimation In DNA Methylation Studies Using Human Placental Tissue

Author

Katri Räikkönen, Cristiana Cruceanu, Thorsten Braun, Andreas Plagemann, Johan G. Eriksson, Linda Dieckmann, Rebecca C. Rancourt, Sara Sammallahti, Marius Lahti-Pulkkinen, Sonja Entringer, Jari Lahti, Hannele Laivuori, Wolfgang Henrich, Eero Kajantie, Sanna Suomalainen-König, Tuomas Kvist, Darina Czamara, Elisabeth B. Binder, and Pia M. Villa

Subjects
Reference free, Cell type, Chemistry, DNA methylation, Placental tissue, Molecular biology
Abstract

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we compare the predictive performance of reference-based versus reference-free estimated proportions of cell types from genome-wide DNAm in placental samples taken at birth and from chorion villus biopsies early in pregnancy using three independent studies comprising over 1,000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.

Published
2021
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40. Preterm Birth, Maternal Postpartum Depressive Symptoms and Mental and Behavioral Disorders in Children

Author

Ville Rantalainen, Dieter Wolke, Marius Lahti-Pulkkinen, Rachel Robinson, Katri Räikkönen, Sakari Lemola, Eero Kajantie, Esa Hämäläinen, Hannele Laivuori, Daniel D. Schnitzlein, Kati Heinonen-Tuomaala, Pia M. Villa, and Polina Girchenko

Subjects
medicine.medical_specialty, Text mining, business.industry, Medicine, business, Psychiatry, Depressive symptoms
Abstract

Introduction Preterm birth has been linked with postpartum depressive (PPD) disorders and high symptoms levels, but evidence remains conflicting and limited in quality. It remains unclear whether PPD symptoms of mothers with preterm babies were already elevated before childbirth, and whether PPD symptoms mediate/aggravate the effect of preterm birth on child mental disorders. We examined whether preterm birth associated with maternal PPD symptoms, depressive symptoms trajectories from antenatal to postpartum stage, and whether PPD symptoms mediated/aggravated associations between preterm birth and child mental disorders. Methods Mothers of preterm(n=125) and term-born(n=3033) children of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study reported depressive symptoms four times within 8 weeks before and twice within 12 months after childbirth. Child mental and behavioral disorder diagnoses until age 8.4-12.8 years came from medical register. ResultsPreterm birth associated with higher PPD symptoms(MD=0.19 SD,95%CI 0.01,0.37,p=0.04), and higher odds(OR=2.23,95%CI 1.22,4.09,p=0.009) of the mother to belong to a group that had consistently high depressive symptoms levels trajectory from antenatal to postpartum stage. PPD symptoms partially mediated and aggravated the association between preterm birth and child mental disorders. ConclusionsPreterm birth, maternal PPD symptoms and child mental disorders are associated, calling for timely prevention interventions.

Published
2021
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41. Prenatal maternal and cord blood vitamin D concentrations and negative affectivity in infancy

Author

Sara, Sammallahti, Elisa, Holmlund-Suila, Runyu, Zou, Saara, Valkama, Jenni, Rosendahl, Maria, Enlund-Cerullo, Helena, Hauta-Alus, Marius, Lahti-Pulkkinen, Hanan, El Marroun, Henning, Tiemeier, Outi, Mäkitie, Sture, Andersson, Katri, Räikkönen, and Kati, Heinonen

Abstract

Higher maternal vitamin D concentration during pregnancy is associated with better child mental health. Negative affectivity, an early-emerging temperamental trait, indicates an increased risk of psychopathology. We investigated if maternal early/mid-pregnancy 25-hydroxyvitamin D (25(OH)D) and neonatal cord blood 25(OH)D concentrations are associated with Negative affectivity in infancy. We studied term-born infants from the vitamin D Intervention in Infants study (VIDI, n = 777, follow-up rate 80%, Finland), and the Generation R Study (n = 1505, follow-up rate 40%, Netherlands). We measured maternal serum 25(OH)D at 6-27 weeks (VIDI) or 18-25 weeks (Generation R) of pregnancy, and cord blood 25(OH)D at birth (both cohorts). Caregivers rated infant Negative affectivity at 11.7 months (VIDI) or 6.5 months (Generation R) using the Revised Infant Behavior Questionnaire. Using linear regression, we tested associations between 25(OH)D and Negative affectivity adjusted for infant age, sex, season of 25(OH)D measurement, maternal age, education, smoking, and body-mass-index. Per 10 nmol/l increase in maternal early/mid-pregnancy 25(OH)D, infant Negative affectivity decreased by 0.02 standard deviations (95% confidence interval [CI] - 0.06, - 0.004) in VIDI, and 0.03 standard deviations (95% CI - 0.03, - 0.01) in Generation R. Cord blood 25(OH)D was associated with Negative affectivity in Generation R (- 0.03, 95% CI - 0.05, - 0.01), but not VIDI (0.00, 95% CI - 0.02, 0.02). Lower maternal 25(OH)D concentrations were consistently associated with higher infant Negative affectivity, while associations between cord blood 25(OH)D concentrations and Negative affectivity were less clear. Maternal vitamin D status during early- and mid-pregnancy may be linked with early-emerging differences in offspring behavior.

Published
2021

42. TH42. APPLICATION OF REFERENCE-BASED CELL TYPE ESTIMATION IN PLACENTAL TISSUE AND COMPARISON WITH A REFERENCE-FREE APPROACH FOR DNA METHYLATION STUDIES

Author

Tuomas Kvist, Eero Kajantie, Andreas Plagemann, Darina Czamara, Jari Lahti, Marius Lahti-Pulkkinen, Katri Räikkönen, Johan G. Eriksson, Sara Sammallahti, Elisabeth B. Binder, Cristiana Cruceanu, Linda Dieckmann, Sonja Entringer, Thorsten Braun, and Rebecca C. Graebig-Rancourt

Subjects
Pharmacology, Reference free, Psychiatry and Mental health, Cell type, Neurology, Chemistry, DNA methylation, Placental tissue, Pharmacology (medical), Neurology (clinical), Molecular biology, Biological Psychiatry
Published
2021
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43. Maternal Hypertensive Pregnancy Disorders and Mental and Behavioral Disorders in the Offspring : a Review

Author

Katri Räikkönen, Marius Lahti-Pulkkinen, Anna Lähdepuro, Ville Rantalainen, Soile Tuovinen, Kati Heinonen, Polina Girchenko, Rachel Robinson, Jari Lahti, Developmental Psychology Research Group, Department of Psychology and Logopedics, Medicum, Behavioural Sciences, University Management, Tampere University, and Welfare Sciences

Subjects
Adult, Etiology, Hypertensive pregnancy, Offspring, 515 Psychology, 3124 Neurology and psychiatry, Preeclampsia, Pregnancy, Risk Factors, 3123 Gynaecology and paediatrics, Internal Medicine, medicine, Prenatal, Humans, Prevention of Hypertension: Public Health Challenges (Y Yano, Section Editor), Psychopathology, business.industry, Mental Disorders, Confounding, Infant, Newborn, Hypertension, Pregnancy-Induced, medicine.disease, Cross-Sectional Studies, 5142 Social policy, Schizophrenia, Prenatal Exposure Delayed Effects, Hypertension, Premature Birth, Female, business, Cohort study, Clinical psychology
Abstract

Purpose of ReviewWe review here recent original research and meta-analytic evidence on the associations of maternal hypertensive pregnancy disorders and mental and behavioral disorders in the offspring.Recent FindingsSeven meta-analyses and 11 of 16 original research studies published since 2015 showed significant associations between maternal hypertensive pregnancy disorders and offspring mental and behavioral disorders. Evidence was most consistent in meta-analyses and high-quality cohort studies. The associations, independent of familial confounding, were observed on different mental and behavioral disorders in childhood and schizophrenia in adulthood. Preterm birth and small-for-gestational age birth emerged as possible moderators and mediators of the associations. Cross-sectional and case-control studies yielded inconsistent findings, but had lower methodological quality.SummaryAccumulating evidence from methodologically sound studies shows that maternal hypertensive pregnancy disorders are associated with an increased risk of mental and behavioral disorders in the offspring in childhood. More studies on adult mental disorders are needed.

Published
2021

44. Maternal antenatal stress and mental and behavioral disorders in their children

Author

Eero Kajantie, Kati Heinonen, Pia M. Villa, Polina Girchenko, Jari Lahti, Katri Räikkönen, Soile Tuovinen, Marius Lahti-Pulkkinen, Rebecca M. Reynolds, Hannele Laivuori, Esa Hämäläinen, Medicum, Developmental Psychology Research Group, Department of Psychology and Logopedics, Faculty Common Matters (Faculty of Medicine), HUSLAB, HUS Gynecology and Obstetrics, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, University of Helsinki, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Pregnancy and Genes, Doctoral Programme in Human Behaviour, Tampere University, Department of Gynaecology and Obstetrics, and Clinical Medicine

Subjects
Male, 515 Psychology, Mothers, Intrauterine growth restriction, Perceived Stress Scale, Anxiety, Mental disorders, 3124 Neurology and psychiatry, Fathers, 03 medical and health sciences, AGE, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Pregnancy, Fetal programming, medicine, Humans, Child, METAANALYSIS, ASSOCIATIONS, Problem Behavior, RISK, business.industry, Depression, Prenatal stress, Center for Epidemiologic Studies Depression Scale, medicine.disease, Anxiety Disorders, BIRTH-WEIGHT, Mental health, Comorbidity, 3. Good health, 030227 psychiatry, Pregnancy Complications, Psychiatry and Mental health, Clinical Psychology, Mood, 5142 Social policy, DEPRESSIVE SYMPTOMS, MOOD, Female, medicine.symptom, business, EARLY-PREGNANCY, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background: Maternal antenatal stress, including symptoms of depression, anxiety and perceived stress, is associated with mental and behavioral problems in children. Whether it is associated with child mental and behavioral disorders remains uncertain. We examined if maternal antenatal symptoms of depression, anxiety and perceived stress were associated with mental and behavioral disorders in their children, if the associations varied according to gestational week, stress type, fluctuating or consistently high symptoms, and if they were driven by maternal or paternal lifetime mood or anxiety disorders. Methods: 3365 mothers participating in the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiologic Studies Depression Scale, the State Anxiety Inventory and the Perceived Stress Scale up to 14 times throughout pregnancy. The Care Register for Health Care provided data on mental and behavioral (including neurodevelopmental) disorders for their children from birth (11/07/2006–07/24/2010) until 12/31/2016 and for parental lifetime mood and anxiety disorders until 12/31/2016. Results: The hazard of any childhood mental and behavioral disorder (HR=1.91, 95% CI: 1.39–2.51) was significantly higher for children whose mothers reported consistently high in comparison to consistently low levels of all types of stress throughout pregnancy. The associations remained significant when adjusted for maternal and paternal lifetime mood and anxiety disorders (and their comorbidity and timing and mood disorder type). Conclusion: Maternal antenatal stress is associated with higher risk of childhood mental and behavioral disorders. Efforts to reduce maternal antenatal stress should be given a high priority to improve child mental health. publishedVersion

Published
2021
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45. Child Polygenic Risk for Psychiatric Disorders Does Not Explain the Association Between Antenatal Maternal Symptoms of Depression and Child Mental Health

Author

Marius Lahti-Pulkkinen, Kieran J. O’Donnell, Irina Pokhvisneva, Katri Räikkönen, Michael J. Meaney, Tuomas Kvist, Vivette Glover, Patrícia Pelufo Silveira, Thomas G. O'Connor, Lawrence M. Chen, Carine Parent, and Jari Lahti

Subjects
medicine.medical_specialty, Longitudinal study, 050208 finance, business.industry, Child psychopathology, 05 social sciences, Mental health, 3. Good health, Informed consent, 0502 economics and business, Cohort, Medicine, Anxiety, Early childhood, 050207 economics, medicine.symptom, business, Psychiatry, Depression (differential diagnoses)
Abstract

Background: There is considerable evidence for an association between antenatal maternal symptoms of depression and anxiety and an increased risk for child mental health problems. One possible major factor that has not been given significant attention is the genomic risk for psychiatric disorders, which may confound (e.g., vertical transmission of genetic risk factors from mother to child) or modify the impact of prenatal exposures on symptom development. Using recent advances in polygenic risk scores, we tested the hypothesis that child genomic risk is a confounder or effect modifier of antenatal maternal symptoms of depression or anxiety on child psychopathology. Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large prospective cohort from the United Kingdom with measures of antenatal maternal mood and child mental health data from 4–16 years. We quantified child genomic risk for ADHD, schizophrenia, and depression using established polygenic risk scores. Outcomes were internalising, externalising, and total emotional/behavioural difficulties from childhood to mid-adolescence. We analysed the data longitudinally with generalized estimating equations (n=5,237) with secondary analyses in an independent prospective cohort of children from the Finnish PREDO study (n=514). Findings: Maternal mood and child genomic risk additively predicted mental health symptoms across childhood and into mid-adolescence. There was a robust prediction of child and adolescent mental health from both antenatal maternal depression (Estimate=0·024, 95% CI: 0·019–0·029, p

Published
2021
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46. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.

Subjects
Netherlands Twin Register (NTR), Alcoholism/genetics, Schizophrenia/genetics, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Medicine (miscellaneous), Genome-wide association study, Alcohol use disorder, Anorexia nervosa, Linkage Disequilibrium, ddc:616.89, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Tobacco Use Disorder/genetics, Substance-Related Disorders/genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Factors de risc en les malalties, Bulimia nervosa, Feeding and Eating Disorders/genetics, eating disorders, genetic correlation, substance use, Tobacco Use Disorder, 3. Good health, Fenotip, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Eating disorders, Phenotype, Schizophrenia, Drinking of alcoholic beverages, eating disorder, Consum d'alcohol, Major depressive disorder, medicine.symptom, Depressive Disorder, Major/genetics, eating disorders, genetic correlation, substance use, Clinical psychology, Substance abuse, Risk factors in diseases, Substance-Related Disorders, Polymorphism, Single Nucleotide, Article, Feeding and Eating Disorders, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Genetics, medicine, Humans, Trastorns de la conducta alimentària, 030304 developmental biology, Genetic association, Pharmacology, Depressive Disorder, Major, Binge eating, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SCCO] Cognitive science, medicine.disease, Comorbidity, Twin study, 030227 psychiatry, Abús de substàncies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Genètica, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs

Published
2021
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47. Prenatal maternal and cord blood vitamin D concentrations and negative affectivity in infancy

Author

Elisa Holmlund-Suila, Runyu Zou, Outi Mäkitie, Saara Valkama, Marius Lahti-Pulkkinen, Sture Andersson, Sara Sammallahti, Hanan El Marroun, Kati Heinonen, Jenni Rosendahl, Maria Enlund-Cerullo, Katri Räikkönen, Henning Tiemeier, Helena Hauta-alus, Tampere University, Welfare Sciences, Child and Adolescent Psychiatry / Psychology, and Clinical Psychology

Subjects
medicine.medical_specialty, Negative affectivity, 515 Psychology, Offspring, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Developmental and Educational Psychology, medicine, Vitamin D and neurology, Prenatal, 030212 general & internal medicine, Vitamin D, Temperament, Infant mental health, Nutrition, 2. Zero hunger, Pregnancy, Obstetrics, business.industry, General Medicine, medicine.disease, Confidence interval, 3. Good health, Psychiatry and Mental health, Cord blood, Pediatrics, Perinatology and Child Health, Generation R, business, 030217 neurology & neurosurgery, Psychopathology
Abstract

Higher maternal vitamin D concentration during pregnancy is associated with better child mental health. Negative affectivity, an early-emerging temperamental trait, indicates an increased risk of psychopathology. We investigated if maternal early/mid-pregnancy 25-hydroxyvitamin D (25(OH)D) and neonatal cord blood 25(OH)D concentrations are associated with Negative affectivity in infancy. We studied term-born infants from the vitamin D Intervention in Infants study (VIDI, n = 777, follow-up rate 80%, Finland), and the Generation R Study (n = 1505, follow-up rate 40%, Netherlands). We measured maternal serum 25(OH)D at 6–27 weeks (VIDI) or 18–25 weeks (Generation R) of pregnancy, and cord blood 25(OH)D at birth (both cohorts). Caregivers rated infant Negative affectivity at 11.7 months (VIDI) or 6.5 months (Generation R) using the Revised Infant Behavior Questionnaire. Using linear regression, we tested associations between 25(OH)D and Negative affectivity adjusted for infant age, sex, season of 25(OH)D measurement, maternal age, education, smoking, and body-mass-index. Per 10 nmol/l increase in maternal early/mid-pregnancy 25(OH)D, infant Negative affectivity decreased by 0.02 standard deviations (95% confidence interval [CI] − 0.06, − 0.004) in VIDI, and 0.03 standard deviations (95% CI − 0.03, − 0.01) in Generation R. Cord blood 25(OH)D was associated with Negative affectivity in Generation R (− 0.03, 95% CI − 0.05, − 0.01), but not VIDI (0.00, 95% CI − 0.02, 0.02). Lower maternal 25(OH)D concentrations were consistently associated with higher infant Negative affectivity, while associations between cord blood 25(OH)D concentrations and Negative affectivity were less clear. Maternal vitamin D status during early- and mid-pregnancy may be linked with early-emerging differences in offspring behavior.

Published
2021

48. Prenatal maternal and cord blood vitamin D concentrations and negative affectivity in infancy

Author

S.M. (Sara) Sammallahti, Elisa Holmlund-Suila, R. (Runyu) Zou, Saara Valkama, Jenni Rosendahl, Maria Enlund-Cerullo, Helena Hauta-alus, Marius Lahti-Pulkkinen, H (Hanan) El Marroun, H.W. (Henning) Tiemeier, Outi Mäkitie, Sture Andersson, Katri Raikkönen, Kati Heinonen, S.M. (Sara) Sammallahti, Elisa Holmlund-Suila, R. (Runyu) Zou, Saara Valkama, Jenni Rosendahl, Maria Enlund-Cerullo, Helena Hauta-alus, Marius Lahti-Pulkkinen, H (Hanan) El Marroun, H.W. (Henning) Tiemeier, Outi Mäkitie, Sture Andersson, Katri Raikkönen, and Kati Heinonen

Abstract

Higher maternal vitamin D concentration during pregnancy is associated with better child mental health. Negative affectivity, an early-emerging temperamental trait, indicates an increased risk of psychopathology. We investigated if maternal early/mid-pregnancy 25-hydroxyvitamin D (25(OH)D) and neonatal cord blood 25(OH)D concentrations are associated with Negative affectivity in infancy. We studied term-born infants from the vitamin D Intervention in Infants study (VIDI, n = 777, follow-up rate 80%, Finland), and the Generation R Study (n = 1505, follow-up rate 40%, Netherlands). We measured maternal serum 25(OH)D at 6–27 weeks (VIDI) or 18–25 weeks (Generation R) of pregnancy, and cord blood 25(OH)D at birth (both cohorts). Caregivers rated infant Negative affectivity at 11.7 months (VIDI) or 6.5 months (Generation R) using the Revised Infant Behavior Questionnaire. Using linear regression, we tested associations between 25(OH)D and Negative affectivity adjusted for infant age, sex, season of 25(OH)D measurement, maternal age, education, smoking, and body-mass-index. Per 10 nmol/l increase in maternal early/mid-pregnancy 25(OH)D, infant Negative affectivity decreased by 0.02 standard deviations (95% confidence interval [CI] − 0.06, − 0.004) in VIDI, and 0.03 standard deviations (95% CI − 0.03, − 0.01) in Generation R. Cord blood 25(OH)D was associated with Negative affectivity in Generation R (− 0.03, 95% CI − 0.05, − 0.01), but not VIDI (0.00, 95% CI − 0.02, 0.02). Lower maternal 25(OH)D concentrations were consistently associated with higher infant Negative affectivity, while associations between cord blood 25(OH)D concentrations and Negative affectivity were less clear. Maternal vitamin D status during early- and mid-pregnancy may be linked with early-emerging differences in offspring behavior.

Published
2021
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49. Facet-level changes in mothers’ neuroticism and extraversion from early pregnancy to 6 months post-partum

Author

Sointu Leikas, Marius Lahti-Pulkkinen, and Katri Räikkönen

Subjects
Social Psychology
Abstract

Becoming a parent could be expected to affect personality development, but the existing results on parenthood-personality change connection are mixed. The present study investigated 2445 primi- and multiparous mothers’ facet- and domain-level changes in Neuroticism and Extraversion from early pregnancy to 6 months post-partum, using latent difference score models. The results showed that Excitability and the affective facets of Neuroticism decreased, and the Neuroticism facets Impulsivity and Self-Consciousness increased during the follow-up. Furthermore, mother-perceived child difficult temperament attenuated desirable personality change and amplified the increases in Impulsivity. The results suggested that considering facet-level changes in personality development across significant life events is informative, and that mother-perceived child temperament may represent an important moderator of short-term personality change across the transition to parenthood.

Published
2022
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50. A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

Author

Darina Czamara, Jari Lahti, Marius Lahti-Pulkkinen, Eero Kajantie, Rebecca M. Reynolds, Anna Suarez, Katri Räikkönen, Hannele Laivuori, Pia M. Villa, Anni Malmberg, Polina Girchenko, Janine Arloth, Esa Hämäläinen, Nadine Provencal, Elisabeth B. Binder, Developmental Psychology Research Group, Department of Psychology and Logopedics, HUS Children and Adolescents, Lastentautien yksikkö, Clinicum, Children's Hospital, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Department of Obstetrics and Gynecology, Pregnancy and Genes, Tampere University, Department of Gynaecology and Obstetrics, and Clinical Medicine

Subjects
Pediatrics, Physiology, BMI, Body-mass index, Intrauterine growth restriction, 11β-HSD2, 11-beta-hydroxysteroid-dehydrogenase type 2, Biochemistry, Umbilical cord, STAI, Spielberger state anxiety inventory, 3124 Neurology and psychiatry, lcsh:RC346-429, 0302 clinical medicine, Endocrinology, 3123 Gynaecology and paediatrics, Childhood mental health, GR, Glucocorticoid receptor, Original Research Article, ADHD, Attention deficit/hyperactivity disorder, Prospective cohort study, GRE, Glucocorticoid response element, PREDO, Prediction and prevention of preeclampsia and intrauterine growth restriction, DNAm, DNA methylation, lcsh:QP351-495, 1184 Genetics, developmental biology, physiology, 3. Good health, medicine.anatomical_structure, Biomarker (medicine), Anxiety, medicine.symptom, Polyepigenetic biomarker, ZINB, Zero-inflated negative binomial regression, medicine.medical_specialty, 515 Psychology, HPA-axis, Hypothalamic-pituitary-adrenal axis, HILMO, Care register for health care, Preeclampsia, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Prospective study, Molecular Biology, Glucocorticoids, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Pregnancy, Fetus, Endocrine and Autonomic Systems, business.industry, CES‐D, Center for epidemiologic studies depression scale, medicine.disease, 030227 psychiatry, GC, Glucocorticoid, Cord blood methylation, lcsh:Neurophysiology and neuropsychology, business, 030217 neurology & neurosurgery, Prenatal psychopathology
Abstract

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes. Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583). Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met. Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders. publishedVersion

Published
2020
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