Exposure to unpredictable maternal sensory signals influences cognitive development across species.

Maternal care is a critical determinant of child development. However, our understanding of processes and mechanisms by which maternal behavior influences the developing human brain remains limited. Animal research has illustrated that patterns of sensory information is important in shaping neural circuits during development. Here we examined the relation between degree of predictability of maternal sensory signals early in life and subsequent cognitive function in both humans (n = 128 mother/infant dyads) and rats (n = 12 dams; 28 adolescents). Behaviors of mothers interacting with their offspring were observed in both species, and an entropy rate was calculated as a quantitative measure of degree of predictability of transitions among maternal sensory signals (visual, auditory, and tactile). Human cognitive function was assessed at age 2 y with the Bayley Scales of Infant Development and at age 6.5 y with a hippocampus-dependent delayed-recall task. Rat hippocampus-dependent spatial memory was evaluated on postnatal days 49-60. Early life exposure to unpredictable sensory signals portended poor cognitive performance in both species. The present study provides evidence that predictability of maternal sensory signals early in life impacts cognitive function in both rats and humans. The parallel between experimental animal and observational human data lends support to the argument that predictability of maternal sensory signals causally influences cognitive development.

Validation of Minimally-Invasive Sample Collection Methods for Measurement of Telomere Length.

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva. Methods: TL was measured in 24 healthy young adults using three modes of sample collection for each participant: venous whole blood, finger prick dried blood spot and saliva. Relative TL was measured using quantitative polymerase chain reaction. Results: TL in finger prick dried blood spots (DBS) washighly correlated with TL in whole blood (r = 0.84, p < 0.001). Salivary TL was also correlated with whole blood TL (r = 0.56, p = 0.005), but this association was not as strong as that of dried blood spot TL (Steiger's Z = 2.12, p = 0.034). TL was longer in saliva than in whole blood or DBS (p's < 0.001). Conclusions: These findings have important implications for future study design by supporting the validity of less-invasive methods that can be implemented with vulnerable populations or in the field. Further, these findings aid in interpreting the burgeoning area of biological aging research and may shed light on our understanding of inconsistencies in the empirical literature.

Fetal programming of children's obesity risk.

OBJECTIVE: Childhood obesity affects nearly 17% of children and adolescents in the United States. Increasing evidence indicates that prenatal maternal stress signals influence fetal growth, child obesity, and metabolic risk. Children exhibiting catch-up growth, a rapid and dramatic increase in body size, within the first two years of life are also at an increased risk for developing metabolic disorder and obesity. We evaluate the potential role of the maternal hypothalamic-pituitary-adrenal (HPA) and placental axis in programming risk for child obesity. METHOD: This prospective longitudinal study measured placental corticotropin-releasing hormone (pCRH) and maternal plasma cortisol at 15, 19, 25, 30, and 37 gestational weeks and collected child body mass index (BMI) at birth, 3, 6, 12, and 24 months. Participants included 246 mothers and their healthy children born full term. Each child's BMI percentile (BMIP) was determined using World Health Organization (WHO) standards based on age and sex. Child BMIP profiles from birth to two years of age were characterized using general growth mixture modeling (GGMM). We evaluated whether fetal exposure to placental CRH and maternal cortisol are associated with BMIP profiles. RESULTS: Placental CRH at 30 gestational weeks was highly associated with both BMIP (p<.05) and weight (p<.05) at birth when accounting for gestational age at birth and used as a predictor in modeling BMIP profiles. Maternal cortisol was not associated with child BMIP. GGMM analyses identified four distinct BMIP profiles: typical, rapid increase, delayed increase, and decreasing (See Fig. 2). The typical profile comprised the majority of the sample and maintained BMIP across the first two years. The rapid and delayed increase profiles each exhibit a period of reduced body size followed by BMI catch-up growth. The rapid increase profile exhibited catch-up within the first 12 months while the delayed group showed an initial decrease in BMIP at 3 months and a dramatic increase from 12 to 24 months. The decreasing profile exhibited normal birth weight and BMIP followed by persisting, low BMIP. The members of the rapid and delayed increase profiles were exposed to the highest concentrations of placental CRH at 30 gestational weeks compared to those in the typical profile group (Fig. 3). CONCLUSIONS: Exposure to elevated placental CRH concentrations during the third trimester is associated with catch-up growth. An early period of small body size followed by rapid catch-up growth is a profile associated with increased metabolic risk and increased obesity risk. Our findings suggest that placental CRH exposure makes a unique contribution to fetal programming of obesity risk.

Early handling attenuates enhancement of glucocorticoid receptors in the prefrontal cortex in an animal model of post-traumatic stress disorder.

BACKGROUND: Changes in glucocorticoid receptors (GRs) have been implicated in the pathogenesis of stress related psychiatric disorders such as depression and post-traumatic stress disorder (PTSD). Abnormal adaptation of the stress-response system following traumatic stress can lead to an altered hypothalamic-pituitary-adrenal axis that may contribute to PTSD development. Indeed, elevated GR expression in the hippocampus and prefrontal cortex linked to PTSD-like characteristics have been reported in the validated animal model of PTSD, single-prolonged stress. These findings implicate increased levels of GRs in the development of post-traumatic psychopathology and suggest that exploration of GR-targeted interventions may have potential for PTSD prevention. Early handling during the neonatal phase alters GR expression and is proposed to confer resilience to stress. We therefore examined the effects of combined early handling and single prolonged stress treatments on GR expression. METHODS: Timed pregnant dams gave birth to pups that were subjected to early handling (n = 11) or control (n = 13) procedures during the neonatal phase. At postnatal day 45 animals underwent single prolonged stress or a control procedure. Rats were euthanized one day later and GR levels were assayed using western blot electrophoresis. RESULTS: Single prolonged stress exposure enhanced GR expression in the hippocampus and prefrontal cortex. Early handling treatment protected against single prolonged stress-induced enhancement of GR expression in the prefrontal cortex, but not in the hippocampus. CONCLUSIONS: These data are a first step in highlighting the importance of targeting GR systems in prevention/resilience and may suggest that preventive strategies targeting GR upregulation might be particularly effective when prefrontal rather than hippocampal GRs are the target.

Congenital adrenal hyperplasia: classification of studies employing psychological endpoints.

Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.