Günter Esser

Behavioral Sequelae of Perinatal Insults and Early Family Adversity at 8 Years of Age

OBJECTIVE This prospective longitudinal study investigated the simultaneous impact of early biological and psychosocial risk factors on behavioral outcome at school age. METHOD A cohort of 362 children born between 1986 and 1988 with different biological (perinatal insults) and psychosocial risk factors (family adversity) was followed from birth to school age. When their children were aged 8 years, parents of 89.0% of the initial sample completed the Child Behavior Checklist (CBCL). RESULTS More externalizing as well as internalizing problems were found in children born into adverse family backgrounds, whereas no differences at broad-band syndrome level were apparent between groups with varying obstetric complications. Children with family risk factors had higher scores on 5 of the 8 CBCL scales (including attention, delinquent, and aggressive problems), whereas children with perinatal risk factors had more social and attention problems than children in the nonrisk groups. With one exception, no interactions between risk factors emerged, indicating that perinatal and family risk factors contributed independently to outcome. The differences between risk groups applied irrespective of gender. CONCLUSIONS The adverse impact of family adversity clearly outweighed the influence of obstetric complications in determining behavioral adjustment at school age.

Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use

BACKGROUND Recent animal research suggests that alterations in the corticotropin releasing hormone receptor 1 (CRHR1) may lead to heavy alcohol use following repeated stress. The aim of this study was to examine interactions between two haplotype-tagging single nucleotide polymorphisms (SNPs) covering the CRHR1 gene and adverse life events on heavy drinking in adolescents. METHODS Data were available from the Mannheim Study of Children at Risk, an ongoing cohort study of the long-term outcome of early risk factors followed since birth. At age 15 years, 280 participants (135 males, 145 females) completed a self-report questionnaire measuring alcohol use and were genotyped for two SNPs (rs242938, rs1876831) of CRHR1. Assessment of negative life events over the past three years was obtained by a standardized interview with the parents. RESULTS Adolescents homozygous for the C allele of rs1876831 drank higher maximum amounts of alcohol per occasion and had greater lifetime rates of heavy drinking in relation to negative life events than individuals carrying the T allele. No gene x environment interactions were found for regular drinking and between rs242938 and stressful life events. CONCLUSIONS These findings provide first evidence in humans that the CRHR1 gene interacts with exposure to stressful life events to predict heavy alcohol use in adolescents.

Epidemiologie psychischer Störungen im Kindes- und Jugendalter:

Zusammenfassung. In der vorliegenden Arbeit wird ein Uberblick uber den aktuellen Wissensstand zur Entwicklungsepidemiologie psychischer Storungen des Kindes- und Jugendalters gegeben. Der Median der Periodenpravalenzraten der wichtigsten Studien betrug 18%, wobei ca. ¾ der Pravalenzraten zwischen 15 und 22% lagen. Damit sind psychische Storungen bei Kindern und Jugendlichen in etwa gleich haufig wie bei Erwachsenen. Als haufigste Storungen zeigten sich Angststorungen mit einer durchschnittlichen Pravalenz von 10,4%, gefolgt von dissozialen Storungen mit 7,5%. Es ergaben sich konsistent hohe Persistenzraten der Storungen von ungefahr 50%, wobei dissoziale Storungen die ungunstigsten Verlaufe aufwiesen. Die haufigsten komorbiden Storungen waren dissoziale Storungen bei Vorliegen einer hyperkinetischen Storung und Angststorungen bei Vorliegen einer depressiven Storung. Bis zum Alter von 13 Jahren wurden durchgehend hohere Gesamtpravalenzen psychischer Storungen bei Jungen gefunden, wogegen im Zuge der Adole...

Differential development of infants at risk for psychopathology: the moderating role of early maternal responsivity.

The development of behaviour problems in infants born with biological risk (low birthweight) and psychosocial risk (psychosocially disadvantaged family) was studied in a sample of 347 children (171 males, 176 females) at the ages of 2, 4:6, and 8 years. In the search for factors that moderate the effects of early risks, the role of early responsive caregiving was examined. Results indicate that infants at psychosocial risk exhibited both more externalizing and internalizing problems across ages than infants not at psychosocial risk, while no overall differences were apparent between normal- and low-birthweight groups. With one exception, no interactions between biological and psychosocial risk factors emerged, suggesting that their simultaneous effect is largely additive. Maternal responsivity was found to moderate the effects of low birthweight on hyperkinetic and internalizing problems as well as to influence the consequences of family disadvantage on total problems. These findings stress the importance of early parenting in the behavioural development of at-risk children.

Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology: evidence from a high-risk community sample of young adults

Previous research examining gene-environment interaction (GxE) with regard to vulnerability to depression and anxiety has yielded conflicting results. The present study was designed to further investigate GxE between 5-HTTLPR and exposure to environmental adversity, using different phenotypic and genotypic characterizations as well as different types of adversity within a prospective study design. Data were available from an ongoing epidemiological cohort study following the outcome of early risk factors from birth to adulthood. At age 19 yr, 309 participants (142 males, 167 females) were characterized on measures of depression and anxiety through interview and questionnaire (DSM-IV diagnosis, Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed at birth (family adversity), and at age 19 yr (stressful life events). Bi- and tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated that depression and anxiety in 19-yr-olds were strongly associated with both family adversity and stressful life events. Individuals with the LL genotype of 5-HTTLPR who were exposed to high family adversity displayed significantly higher rates of depressive or anxiety disorders and had more depressive symptoms than those without either condition. This GxE replicates recent findings from an epidemiological cohort study of adolescents but is in contrast to many previous reports suggesting an interaction with the S allele. No evidence for GxE was obtained with regard to current stressful life events and trait anxiety. One possible source for the conflicting findings might be attributed to heterogeneity in depression phenotypes and environmental adversity.

Interaction of Dopamine Transporter Genotype with Prenatal Smoke Exposure on ADHD Symptoms

OBJECTIVE To demonstrate that children homozygous for the 10-repeat allele of the common dopamine transporter (DAT1) polymorphism who were exposed to maternal prenatal smoke exhibited significantly higher hyperactivity-impulsivity than children without these environmental or genetic risks. STUDY DESIGN We performed a prospective longitudinal study from birth into early adulthood monitoring the long-term outcome of early risk factors. Maternal prenatal smoking was determined during a standardized interview with the mother when the child was 3 months old. At age 15 years, 305 adolescents participated in genotyping for the DAT1 40 base pair variable number of tandem repeats polymorphism and assessment of inattention, hyperactivity-impulsivity, and oppositional defiant/conduct disorder symptoms with the Kiddie-Sads-Present and Lifetime Version. RESULTS There was no bivariate association between DAT1 genotype, prenatal smoke exposure and symptoms of attention deficit hyperactivity disorder. However, a significant interaction between DAT1 genotype and prenatal smoke exposure emerged (P = .012), indicating that males with prenatal smoke exposure who were homozygous for the DAT1 10r allele had higher hyperactivity-impulsivity than males from all other groups. In females, no significant main effects of DAT1 genotype or prenatal smoke exposure or interaction effects on any symptoms were evident (all P > .25). CONCLUSIONS This study provides further evidence for the multifactorial nature of attention deficit hyperactivity disorder and the importance of studying both genetic and environmental factors and their interaction.

Impact of Psychosocial Adversity on Alcohol Intake in Young Adults: Moderation by the LL Genotype of the Serotonin Transporter Polymorphism

BACKGROUND Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G x E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults. METHODS Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events). RESULTS In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity. CONCLUSIONS One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression.

Längsschnittforschung zur Entwicklungsepidemiologie psychischer Störungen: Zielsetzung, Konzeption und zentrale Befunde der Mannheimer Risikokinderstudie

Zusammenfassung. Theoretischer Hintergrund: Zur Erforschung der Entwicklungsepidemiologie psychischer Storungen gilt die prospektive Untersuchung von Risikogruppen als Konigsweg. Fragestellung: Bes...

Negative association between plasma cortisol levels and aggression in a high-risk community sample of adolescents

In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.

Child development after maternal tocolysis with beta-sympathomimetic drugs.

The psycho-social development of both preterm and term children whose mothers reported tocolytic treatment was assessed at the ages of 2, 4.5, and 8 years. Term children exposed to tocolysis showed a higher rate of psychiatric disorders as well as poorer cognitive and motor perfomance than controls. In the preterm children no adverse impact of tocolysis could be found. The results are discussed concerning possible ways in which tocolytic treatment may influence child development. Restrictions because of the preliminary character of this study and the need of further prospective studies to clarify the developmental impact of tocolysis are also considered.