Prenatal glucocorticoid exposure has been negatively associated with infant neurocognitive outcomes. However, questions about developmental timing effects across gestation remain. Participants were 253 mother-child dyads who participated in a prospective cohort study recruited in the first trimester of pregnancy. Diurnal cortisol was measured in maternal saliva samples collected across a single day within each trimester of pregnancy. Children (49.8% female) completed the Bayley Mental Development Scales, Third Edition at 6, 12, and 24 months and completed three observational executive function tasks at 24 months. Structural equation models adjusting for sociodemographic covariates were used to test study hypotheses. There was significant evidence for timing sensitivity. First-trimester diurnal cortisol (area under the curve) was negatively associated with cognitive and language development at 12 months and poorer inhibition at 24 months. Second-trimester cortisol exposure was negatively associated with language scores at 24 months. Third-trimester cortisol positively predicted performance in shifting between task rules (set shifting) at 24 months. Associations were not reliably moderated by child sex. Findings suggest that neurocognitive development is sensitive to prenatal glucocorticoid exposure as early as the first trimester and underscore the importance of assessing developmental timing in research on prenatal exposures for child health outcomes.

High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.

Institutionally deprived young children often display distinctive patterns of attachment, classified as insecure/other (INS/OTH), with their adoptive parents. The associations between INS/OTH and developmental trajectories of mental health and neurodevelopmental symptoms were examined. Age 4 attachment status was determined for 97 Romanian adoptees exposed to up to 24 months of deprivation in Romanian orphanages and 49 nondeprived UK adoptees. Autism, inattention/overactivity and disinhibited-social-engagement symptoms, emotional problems, and IQ were measured at 4, 6, 11, and 15 years and in young adulthood. Romanian adoptees with over 6 months deprivation (Rom>6) were more often classified as INS/OTH than UK and Romanian adoptees with less than 6 months deprivation combined. INS/OTH was associated with cognitive impairment at age 4 years. The interaction between deprivation, attachment status, and age for autism spectrum disorder assessment was significant, with greater symptom persistence in Rom>6 INS/OTH(+) than other groups. This effect was reduced when IQ at age 4 was controlled for. Age 4 INS/OTH in Rom>6 was associated with worse autism spectrum disorder outcomes up to two decades later. Its association with cognitive impairment at age 4 is consistent with INS/OTH being an early marker of this negative developmental trajectory, rather than its cause.

Objectives: Individuals with moderate–severe traumatic brain injury (TBI) experience a transitory state of impaired consciousness and confusion often called posttraumatic confusional state (PTCS). This study examined the neuropsychological profile of PTCS. Methods: Neuropsychometric profiles of 349 individuals in the TBI Model Systems National Database were examined 4 weeks post-TBI (±2 weeks). The PTCS group was subdivided into Low (n=46) and High Performing PTCS (n=45) via median split on an orientation/amnesia measure, and compared to participants who had emerged from PTCS (n=258). Neuropsychological patterns were examined using multivariate analyses of variance and mixed model analyses of covariance. Results: All groups were globally impaired, but severity differed across groups (F(40,506)=3.44; p<.001; ŋp2 =.206). Rate of forgetting (memory consolidation) was impaired in all groups, but failed to differentiate them (F(4,684)=0.46; p=.762). In contrast, executive memory control was significantly more impaired in PTCS groups than the emerged group: Intrusion errors: F(2,343)=8.78; p<.001; ŋp2=.049; False positive recognition errors: F(2,343)=3.70; p<.05; ŋp2=.021. However, non-memory executive control and other executive memory processes did not differentiate those in versus emerged from PTCS. Conclusions: Executive memory control deficits in the context of globally impaired cognition characterize PTCS. This pattern differentiates individuals in and emerged from PTCS during the acute recovery period following TBI. (JINS, 2019, 25, 302–313)

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

There is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene–environment interactions, epigenetics, and specific systems including the hypothalamic–pituitary–adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that “wife beating” was justified compared with 2.0% in Argentina). There may be interactions with nutritional deficiencies or with extremes of temperature. Prenatal stress alters the microbiome, and this can differ in different countries. Genetic differences in different ethnic groups may make some more vulnerable or more resilient to the effects of prenatal stress on child neurodevelopment. Most research on these questions has been in predominantly Caucasian samples from high-income countries. It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.

In 785 mother–child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7–15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7–15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.

There is now a clear focus on incorporating, and integrating, multiple levels of analysis in developmental science. The current study adds to research in this area by including markers of the immune and neuroendocrine systems in a longitudinal study of temperament in infants. Observational and parent-reported ratings of infant temperament, serum markers of the innate immune system, and cortisol reactivity from repeated salivary collections were examined in a sample of 123 infants who were assessed at 6 months and again when they were, on average, 17 months old. Blood from venipuncture was collected for analyses of nine select innate immune cytokines; salivary cortisol collected prior to and 15 min and 30 min following a physical exam including blood draw was used as an index of neuroendocrine functioning. Analyses indicated fairly minimal significant associations between biological markers and temperament at 6 months. However, by 17 months of age, we found reliable and nonoverlapping associations between observed fearful temperament and biological markers of the immune and neuroendocrine systems. The findings provide some of the earliest evidence of robust biological correlates of fear behavior with the immune system, and identify possible immune and neuroendocrine mechanisms for understanding the origins of behavioral development.

Genetic variation in the oxytocin receptor gene (OXTR) is associated with several psychiatric conditions characterized by deficits in executive functioning (EF). A specific OXTR variant, rs2254298, has previously been associated with brain functioning in regions implicated in EF. Moreover, birth weight variation across the entire range is associated with individual differences in cortical structure and function that underlie EF. This is the first study to examine the main and interactive effect between rs2254298 and birth weight on EF in children. The sample consisted of 310 children from an ongoing longitudinal study. EF was measured at age 4.5 using observational tasks indexing working memory, cognitive flexibility, and inhibitory control. A family-based design that controlled for population admixture, stratification, and nongenomic confounds was employed. A significant genetic association between rs2254298 and EF was observed, with more copies of the major allele (G) associated with higher EF. There was also a significant interaction between rs2254298 and birth weight, such that more copies of the major allele in combination with higher birth weight predicted better EF. Findings suggest that OXTR may be associated with discrete neurocognitive abilities in childhood, and these effects may be modulated by intrauterine conditions related to fetal growth and development.

Optical luminescence dates for 19 samples from the degraded linear dune field of western Zambia indicate multiple periods of regional dune building for the late Quaternary, 32,000–27,000, 16,000–13,000, 10,000–8000, and 5000–4000 yr ago. These dates show that the last glacial maximum was not the only time when dune construction, commonly linked to marked aridity, occurred in central-southern Africa during the late Quaternary. Whereas rainfall significantly less than today's ca. 1400 mm yr−1 is a prerequisite for dune construction in the area, adequate sediment supply also determines dune construction and preservation, so that dune building cannot be simply and singularly linked to marked aridity. The Zambezi River system is proposed as an important source of dune sediments, with the nature of linear dune activity explaining why stacked sediments preserve several phases of dune formation. Chronologies of dune construction in western Zimbabwe and the southwest Kalahari are in broad agreement with our Zambian chronology and support a model of rainfall shifts along a SW–NE gradient, with some notable disparities. These are probably a function of interregional sediment supply differences, the number of samples used to delimit constructional periods, and the multicausal nature of forcing mechanisms.

Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system–brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

Multiple behavioral and health outcomes, including internalizing symptoms, may be predicted from prenatal maternal anxiety, depression, or stress. However, not all children are affected, and those that are can be affected in different ways. Here we test the hypothesis that the effects of prenatal anxiety are moderated by genetic variation in the child's brain-derived neurotrophic factor (BDNF) gene, using the Avon Longitudinal Study of Parents and Children population cohort. Internalizing symptoms were assessed from 4 to 13 years of age using the Strengths and Difficulties Questionnaire (n = 8,584); a clinical interview with the adolescents was conducted at age 15 years (n = 4,704). Obstetric and psychosocial risk and postnatal maternal symptoms were included as covariates. Results show that prenatal maternal anxiety predicted internalizing symptoms, including with the diagnostic assessment at 15 years. There was a main effect of two BDNF polymorphisms (rs6265 [val66met] and rs11030104) on internalizing symptoms up to age 13. There was also genetic moderation of the prenatal anxiety effect by different BDNF polymorphisms (rs11030121 and rs7124442), although significant effects were limited to preadolescence. The findings suggest a role for BDNF gene–environment interactions in individual vulnerability to the effects of prenatal anxiety on child internalizing symptoms.

Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre- and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis.