Early Life Origins of Severe Personality Disorders : The Helsinki Birth Cohort Study

Previous studies suggest that a suboptimal early life environment may predict an increased risk of adult personality disorders. However, most of this evidence is based on studies with retrospective accounts of early adversity. This retrospective design may induce a bias and hinder interpretation of the direction of causality. This thesis examines, in a longitudinal study setting, the developmental origins of personality disorders severe enough to justify hospitalisation. The focus is on pre- and postnatal growth and on parental separation in childhood due to temporary evacuations from Finland during World War II in the etiology of both any and dramatic personality disorders requiring hospitalisation. The study cohort is the Helsinki Birth Cohort Study, which comprises 13,345 individuals born 1934-1944. Data on early life growth, on childhood evacuations, and on the diagnoses of personality disorders were drawn from birth- and child welfare records and national registers. These objective record- and register-based data enabled the longitudinal design of the studies. In the current study cohort, there were 1,781 individuals who had been separated from their parents in childhood. There were 202 subjects who had been hospitalised for personality disorders, and 77 individuals with dramatic personality disorders. The results showed that a small head circumference and a small head-to-length ratio at birth predicted an increased risk of any severe personality disorder among men and a small placental surface area at birth predicted dramatic personality disorders among women. Slower gain in BMI between birth and six months of age, faster gains in weight and in BMI between six months and one year, and slower gains in weight and in BMI between seven and 11 years of age also predicted personality disorders among men. Slower height growth between two and seven years of age predicted an increased risk of personality disorders among women. The associations between infancy and childhood growth and severe personality disorders among men were especially characteristic of dramatic personality disorders, and were independent of comorbid mood disorders. Temporary separation from parents, particularly in the first five years of life, predicted an increased risk of severe personality disorders, and among men, of dramatic personality disorders. The effects of early parental separation were specific to personality disorders, since they emerged in comparisons to both healthy control participants and to individuals with other mental disorders. These longitudinal study findings strongly support an etiological role for early life, both pre- and postnatal, environmental adversity in the development of severe personality disorders, especially dramatic personality disorders. Vulnerability to severe personality disorders is developmentally programmed in early life.Varhaiskehitykselliset tekijät ennustavat vakavien persoonallisuushäiriöiden riskiä aikuisiällä Tämän pitkittäistutkimuksen tulokset tukevat vahvasti varhaiskehityksen vaikeuksien ennustavaa roolia vakavien persoonallisuushäiriöiden kehittymisessä. Vanhemmistaan lapsuudessa eroon joutuneilla sotalapsilla oli kohonnut vakavien, sairaalahoitoa vaatineiden persoonallisuus- ja päihdehäiriöiden riski aikuisiällä. Riski oli erityisen kohonnut, jos lapsi oli joutunut eroon vanhemmistaan viiden ensimmäisen elinvuoden aikana. Myös hidastunutta aivojen kasvua sikiöaikana heijastava pienempi päänympärys syntymähetkellä ennusti miehillä kohonnutta vakavien persoonallisuushäiriöiden riskiä aikuisiällä. Lisäksi kasvupoikkeamat painoindeksissä ja painossa sekä ensimmäisen elinvuoden aikana että kouluiässä ennustivat vakavia persoonallisuushäiriöitä miehillä, kun taas naisilla niitä ennusti hitaampi pituuskasvu leikki-iässä. Tulokset varhaiskehityksen vaikeuksien vaikutuksista persoonallisuushäiriöiden kehittymiseen ovat kansanterveydellisesti tärkeitä. Persoonallisuushäiriöt ovat vakavia, pitkäkestoisia mielenterveyden häiriöitä. Niihin liittyy vaikeuksia niin vuorovaikutuksellinen kuin sekä tunne- että työelämässä pärjäämisen osalta. Persoonallisuushäiriöt ennustavat kohonnutta ennenaikaisen kuolleisuuden riskiä, ja ovat yhteydessä suurempaan itsemurhien ja sydän- ja verisuonitautien riskiin. Persoonallisuushäiriöiden kehityksellisten ennustajien tunnistamisen kautta voidaan kehittää häiriöitä ennaltaehkäiseviä interventioita ja tunnistaa juuri ne lapset, ketkä voisivat hyötyä interventiosta. Tämän väitöskirjan tulosten perusteella ennustavia tekijöitä on tunnistettavissa useita jo varhaislapsuudessa. Tutkimuskohorttina toimi Helsingin Syntymäkohortti, johon kuuluu 13345 vuosina 1934-1944 syntynyttä suomalaista. Tiedot kasvusta, lapsuusiän erokokemuksista, sekä persoonallisuushäiriödiagnooseista saatiin terveydenhuollon korteista ja kansallisista rekistereistä, mikä mahdollisti tutkimuksen pitkittäisotteen. Otoksen diagnostinen seuranta kesti 35 vuotta aikuisiällä. Tänä aikana 202 kohortin jäsentä oli joutunut sairaalahoitoon persoonallisuushäiriön takia. Vanhemmistaan eroon joutuneita sotalapsia kohortissa oli 1781

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

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 <0.01) and met/met (A: A) groups (all p <0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.Peer reviewe

Maternal Hypertensive Pregnancy Disorders and Mental and Behavioral Disorders in the Offspring : a Review

Purpose of Review We 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 Findings Seven 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. Summary Accumulating 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.Peer reviewe

The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood

Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95%CI = 0.20-0.46); B = 0.10 (95%CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.Peer reviewe

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

Introduction The 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 methods Using 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. Results Lower 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), pPeer reviewe

Intergenerational Transmission of Birth Weight Across 3 Generations

While previous studies have shown intergenerational transmission of birth weight from mother to child, whether the continuity persists across 3 generations has rarely been assessed. We used the Aberdeen Maternity and Neonatal Data-bank (United Kingdom) to examine the intergenerational correlations of birth weight, birth weight adjusted for gestational age and sex, and small- and large-for-gestational-age births across 3 generations among 1,457 grandmother-mother-child triads. All participants were born between 1950 and 2015. The intergenerational transmission was examined with linear regression analyses. We found that grandmaternal birth weight was associated with grandchild birth weight, independently of prenatal and sociodemographic covariates and maternal birth weight (B = 0.12 standard deviation units, 95% confidence interval: 0.07, 0.18). Similar intergenerational continuity was found for birth weight adjusted for sex and gestational age as well as for small-for-gestational-age births. In conclusion, birth weight and fetal growth showed intergenerational continuity across 3 generations. This supports the hypothesis that the developmental origins of birth weight and hence later health and disease are already present in earlier generations.Peer reviewe

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

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

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.Peer reviewe

Maternal depressive symptoms during and after pregnancy are associated with poorer sleep quantity and quality and sleep disorders in 3.5-year-old offspring

Objective: Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. Methods: A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks thorn days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child's mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory-II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. Results: Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. Conclusion: Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Maternal Depressive Symptoms During and After Pregnancy and Psychiatric Problems in Children

OBJECTIVE: Maternal depressive symptoms during pregnancy are associated with increased risk of psychiatric problems in children. A more precise understanding of the timing of the symptoms during pregnancy and their independence of other prenatal and postnatal factors in predicting child psychopathology risk is needed. We examined whether maternal depressive symptoms during pregnancy predict child psychiatric problems, whether these associations are trimester- or gestational-week-specific and/or independent of pregnancy disorders, and whether maternal depressive symptoms after pregnancy mediate or add to the prenatal effects. METHOD: The study sample comprised 2,296 women and their children born in Finland between 2006-2010, participating in the prospective pregnancy cohort study Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) and followed up from 1.9 to 5.9 years of age. The women completed the Center for Epidemiologic Studies Depression Scale biweekly between gestational weeks+days 12+0/13+6 and 38+0/39+6 or delivery. In the follow-up, they completed the Beck Depression Inventory-II and Child Behavior Checklist 1½-5. RESULTS: Maternal depressive symptoms during pregnancy predicted significantly higher internalizing (0.28 SD unit per SD unit increase [95% CI = 0.24-0.32]), externalizing (0.26 [0.23-0.30]), and total problems (0.31 [0.27-0.35]) in children. These associations were nonspecific to gestational week and hence pregnancy trimester, independent of pregnancy disorders, and independent of, although partially mediated by, maternal depressive symptoms after pregnancy. Psychiatric problems were greatest in children whose mothers reported clinically significant depressive symptoms across pregnancy trimesters and during and after pregnancy. CONCLUSION: Maternal depressive symptoms during pregnancy predict increased psychiatric problems in young children. Preventive interventions from early pregnancy onward may benefit offspring mental health.Peer reviewe