Anja C. Huizink

Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility?

This review focuses on prenatal stress as a risk factor for psychopathology. Evidence from animal studies is summarized, and the relevance of prenatal stress models in animals for human studies is discussed. In the offspring of prenatally stressed animals, overactivity and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal axis are consistent findings and may reflect a pathophysiological mechanism involved in the development of psychopathology. Reduced activity of the opioid GABA/benzodiazepine, serotonin, and dopamine systems and increased activity of the sympathico-adrenal system have been found as well. These alterations have been linked to a diverse spectrum of psychopathology. Therefore, the evidence supports the view that exposure to prenatal stress may result in a general susceptibility to psychopathology, rather than exerting a direct effect on a specific form of psychopathology.

Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring.

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

Cohort Profile: The Dutch ‘TRacking Adolescents’ Individual Lives’ Survey’; TRAILS

Mental disorders account for one-fifth of the total burden of disease in the Western world, 1 and, as such, should require due attention from the international epidemiological research community. Good quality research on the aetiology and course of psychopathology in the population is impossible without reliable and valid data from long-term longitudinal cohort studies. Research on psychopathology in adolescence is important both from a scientific point of view and from the point of view of prevention and public health policy. Adolescence is characterized by major biological, psychological and social challenges and opportunities, where interaction between the individual and environment is intense, and developmental pathways are set in motion or become established. 2–4 Furthermore, adolescent psychopathology can have important consequences for education, relationships and socioeconomic achievement in later life. 5–7 These characteristics of adolescence do not only set high demands for cohort studies aiming to capture the most salient aspects of developmental pathways, they also ensure a great gain in empirical knowledge and an invaluable source of information for public health policy from such studies. In order to fully benefit from this potential, a multidisciplinary approach is essential.

The effects of prenatal stress on temperament and problem behavior of 27-month-old toddlers

AimTo examine, in a prospective study, the influence of prenatal stress on infant temperament and problem behavior.MethodSelf-report data on stress and anxiety, and levels of cortisol in saliva were collected from nulli-parous women during pregnancy. Temperament of the child was measured at 27 months by parent report on the Infant Characteristics Questionnaire. Behavior of the child was assessed by direct observation during the administration of the Bayley Scales of Development 2–30, and by parent report on the Child Behavior Checklist 2–3.ResultsComplete data were available for 103 healthy toddlers. Logistic regression analyses were performed and results were adjusted for possible prenatal, perinatal and postnatal confounders. Perceived stress during pregnancy was a predictor of lower levels of restless/disruptive temperament (OR=0.77), more total behavioral problems (OR=1.17), and more externalizing behavioral problems (OR=1.12) in 2-year-olds. Fear of bearing a handicapped child was a predictor of higher levels of restless/disruptive temperament (OR=1.39) and more attention regulation problems in toddlers (OR=1.46).ConclusionsIncreased levels of maternal prenatal stress appear to be associated with temperamental and behavioral problems in toddlers.

A systematic review of prospective studies on attention problems and academic achievement

Polderman TJC, Boomsma DI, Bartels M, Verhulst FC, Huizink AC. A systematic review of prospective studies on attention problems and academic achievement.

The developmental course of anxiety symptoms during adolescence: The TRAILS study

BACKGROUND Little is known about the development of anxiety symptoms from late childhood to late adolescence. The present study determined developmental trajectories of symptoms of separation anxiety disorder (SAD), social phobia (SoPh), generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD) in a large prospective community cohort. METHODS Anxiety symptoms were assessed in a community sample of 2220 boys and girls at three time-points across a 5-year interval. The Revised Child Anxiety and Depression Scale (RCADS) was used to assess anxiety symptoms, and multilevel growth-curve analyses were performed. RESULTS All subtypes of anxiety first showed a decrease in symptoms (beta for age ranged from -.05 to -.13, p < .0001), followed by a leveling off of the decrease, and a subsequent slight increase in symptoms (beta for age-squared ranged from .006 to .01, p < .0001) from middle adolescence (GAD, SoPh, SAD) or late adolescence (PD and OCD) onwards. This increase in anxiety symptoms could not be explained by a co-occurring increase in depression symptoms. Girls had more anxiety symptoms than boys, and this difference remained stable during adolescence (p < .0001). Gender differences were strongly attenuated by adjustment for symptoms of depression. CONCLUSIONS The current study shows that, in the general population, anxiety symptoms first decrease during early adolescence, and subsequently increase from middle to late adolescence. These findings extend our knowledge on the developmental course of anxiety symptoms during adolescence. This is the first study to separate the development of anxiety symptoms from that of symptoms of depression.

Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study

OBJECTIVE Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use and fetal growth until birth in a population-based sample. METHOD Approximately 7,452 mothers enrolled during pregnancy and provided information on substance use and fetal growth. Fetal growth was determined using ultrasound measures in early, mid-, and late pregnancy. Additionally, birth weight was assessed. RESULTS Maternal cannabis use during pregnancy was associated with growth restriction in mid-and late pregnancy and with lower birth weight. This growth reduction was most pronounced for fetuses exposed to continued maternal cannabis use during pregnancy. Fetal weight in cannabis-exposed fetuses showed a growth reduction of -14.44 g/week (95% confidence interval -22.94 to -5.94, p = .001) and head circumference (-0.21 mm/week, 95% confidence interval -0.42 to 0.02, p = .07), compared with nonexposed fetuses. Maternal cannabis use during pregnancy resulted in more pronounced growth restriction than maternal tobacco use. Paternal cannabis use was not associated with fetal growth restriction. CONCLUSIONS Maternal cannabis use, even for a short period, may be associated with several adverse fetal growth trajectories.

Role of individual, peer and family factors in the use of cannabis and other illicit drugs: A longitudinal analysis among Finnish adolescent twins

BACKGROUND Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. METHODS We used longitudinal data from the FinnTwin12-17 study with baseline at age 11-12 and follow-up at ages 14 and 17(1/2), including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17(1/2). The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use. RESULTS 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 17(1/2). When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intoxication, having smoking peers and acquaintances with drug experience, fathers weekly drinking to intoxication, and aggressive behavior among boys. Smoking initiation by age of 12 was the most powerful predictor among individuals (OR=26, p<0.001) and within discordant pairs (OR=22, p<0.001). CONCLUSIONS Early onset smoking is a powerful predictor for subsequent use of illicit drugs among Finnish adolescents, but the causal nature of this relationship needs to be clarified.

Chernobyl exposure as stressor during pregnancy and hormone levels in adolescent offspring

Background: Animal research suggests a programming effect of prenatal stress in the fetal period, resulting in disruptions in behavioural and neuromotor development. Physiological changes that mediate these effects include alterations in the hypothalamic-pituitary-adrenal axis and in testosterone levels. This human study focuses on changes related to these physiological systems after prenatal stress exposure. Methods: We examined the potential effect of prenatal stress associated with the Chernobyl disaster in an ongoing genetic epidemiological study in Finland. One birth cohort of twins (n = 121 twin pairs) was exposed in utero to maternal stress, and their saliva cortisol and testosterone levels at age 14 were compared with twins (n = 157 twin pairs) born one year later. Results: Cortisol levels in both sexes and testosterone levels among females were significantly elevated after prenatal exposure to maternal stress from the second trimester onwards, compared to reference groups of non-exposed adolescents. Exposure explains 3% of variance (p<0.05) in cortisol levels and 18% of variance in testosterone levels (p<0.001). No significant differences were found for exposure from either first or third trimester onwards. Conclusion: Our results suggest that prenatal exposure to maternal stress in the second trimester of pregnancy may have resulted in prenatal programming of physiological systems relating to cortisol and testosterone levels.

Prenatal cannabis exposure and infant outcomes: overview of studies.

Accumulating evidence from both human and preclinical studies indicates maternal substance use during pregnancy can affect fetal development, birth weight and infant outcomes. Thus, the prenatal period can be regarded as an important and potentially sensitive period of development. In this manuscript, an updated overview of studies on prenatal cannabis exposure in humans is presented, including recent studies conducted within the Generation R study. Findings on fetal growth, birth outcomes, early neonatal behavior and infant behavior and cognitive development are discussed in detail. Preclinical evidence and potential mechanisms are described as well, and recommendations for future studies are provided. It is concluded that evidence seems to suggest that fetal development is affected by prenatal maternal cannabis use, while findings on effects on infant behavior or cognition are inconsistent. Beyond infancy, subtle differences may be found in specific cognitive or behavioral outcomes, although replication studies in which pregnant women and their fetuses are exposed to current and probably higher levels of Δ9-tetrahydrocannabinol and novel designs are needed to come to firm conclusions.