Sensitive Periods Of Development Research Articles

Early socioeconomic circumstances and cardiometabolic health in 10-year-old children

Abstract Background Social adversity is thought to become biologically embedded during sensitive periods of development, setting children on a trajectory of increased risk for later chronic diseases. Thus, social differences are expected to be expressed as biological alterations and might have their origins in early life. Therefore, we aim to estimate the association between early socioeconomic position (SEP) and cardiometabolic health during childhood. Methods Data from 2962 participants in the population-based birth cohort Generation XXI, from Porto, Portugal, was collected following standardized procedures at all study waves. Early SEP definition included household income, parental education and occupation at child’s birth. Cardiometabolic health was characterized at the age of 7 and 10, considering the triglycerides, cholesterol, fasting glucose, body mass index, systolic and diastolic blood pressure. Logistic regression was used to estimate the association between early SEP and a favorable cardiometabolic health profile. Results A favorable cardiometabolic profile was observed in almost half of participants at both ages, particularly among high SEP children who remain more frequently without alterations. For girls, higher paternal education at 7 years (OR:1.49;95%CI:1.03-2.15) and higher SEP at 10 were associated with better cardiometabolic health profile. In boys, a better cardiometabolic health profile was observed with increasing levels in maternal and paternal education and occupation, but at the age of 10, social differences were more evident according to parental education. Conclusions We provide evidence that children from more advantaged SEP at birth have an increased likelihood of presenting better cardiometabolic health at early ages. Social differences in cardiometabolic health biomarkers are already found in childhood, suggesting that the short-term impact of early life SEP on the physiology dysregulation takes place already in the first decade of life. Key messages Social differences in cardiometabolic health are already established in the first decade of life, with children from higher SEP presenting a better cardiometabolic health. Cardiovascular events are not expected to develop during childhood, however the underlying atherosclerotic process might already be in course as social differences appear to widen with age.

Удосконалення спеціальної фізичної підготовки гімнасток у спортивній аеробіці на етапі початкової підготовки

Galyna Artem i eva , Inna Bodrenkova & Tetiana Moshenska Competition is intensifying on the world platform, competitive activity is becoming more complex, requirements for the performing skills of athletes are being raised, special requirements are being placed on the level of special physical fitness of gymnasts, and it is becoming increasingly difficult to win. There are new problems that leading experts associate with the process of many years of sports training. Now in sports aerobics (aerobic gymnastics) there is the problem of developing special physical qualities of athletes, starting from the initial training stage. Also, the issues of selecting adequate means and methods have not been sufficiently resolved, their rational combination in the training process, taking into account the specificity of the competitive activity of this sport, modern refereeing and tasks of this stage. Purpose: theoretically develop and experimentally substantiate the methodology for improving the special physical training of gymnasts in sports aerobics at the initial training stage. Material & Methods: a complex of scientific research methods (pedagogical research methods and methods of mathematical statistics) was used. 32 athletes (7–8 years old, girls) took part in the experimental part. Two groups were formed (control – 16 girls, and the main – 16 girls). Results: through the use of an experimental technique, selection of funds and the optimal combination of loads, taking into account the age characteristics of young athletes, an increase in physical performance was obtained, the physical and functional preparedness of the gymnasts of the main group increased. Conclusions: the developed methodology for improving the special physical training of gymnasts 7–8 years old, who are engaged in sports aerobics (aerobic gymnastics), ensures the growth of physical capabilities of athletes, solves the main tasks of the training stage, based on the specifics of motor activity, sensitive periods of development of physical qualities in this form sports, contributes to comprehensive physical development, integrated physical preparedness, the laying of a specific functional base for effective of learning technology.

A rapid assay of human thyroid peroxidase activity

Impaired synthesis or action of thyroid hormones (THs) during critically sensitive periods of development can have long term adverse effects on health. Development of rapid assays to identify chemicals that impair THs physiology is an important goal for reducing risks from chemical use. Thyroid peroxidase (TPO) is a key enzyme regulating THs synthesis in thyroid gland and a vulnerable target for chemicals that disrupt THs synthesis. To develop a human-relevant, rapid assay for TPO inhibition, we have engineered two cell lines (CHO and LentiX- 293) to express active human TPO (hTPO) enzyme and applied them in a recently-described assay using a stable fluorescent product (Amplex UltraRed). Assay performance was assessed by comparing activity of 19 reference chemicals with known strong, weak or no TPO inhibitory activity. The assay using hTPO from either cell line consistently identified the relative potency of strong to moderate inhibitors and chemicals known to be inactive. Results were less consistent for chemicals reported to be weak inhibitors of rodent TPO, possibly suggesting some species specificity. Our studies support the use of hTPO from stably transfected cell lines to substitute for animal-derived thyroid microsomes for rapid high throughput screening assays to identify and characterize TPO inhibitors.

Early-life adversity and neurological disease: age-old questions and novel answers.

Neurological illnesses, including cognitive impairment, memory decline and dementia, affect over 50 million people worldwide, imposing a substantial burden on individuals and society. These disorders arise from a combination of genetic, environmental and experiential factors, with the latter two factors having the greatest impact during sensitive periods in development. In this Review, we focus on the contribution of adverse early-life experiences to aberrant brain maturation, which might underlie vulnerability to cognitive brain disorders. Specifically, we draw on recent robust discoveries from diverse disciplines, encompassing human studies and experimental models. These discoveries suggest that early-life adversity, especially in the perinatal period, influences the maturation of brain circuits involved in cognition. Importantly, new findings suggest that fragmented and unpredictable environmental and parental signals comprise a novel potent type of adversity, which contributes to subsequent vulnerabilities to cognitive illnesses via mechanisms involving disordered maturation of brain 'wiring'.

Delta-9-THC exposure during zebra finch sensorimotor vocal learning increases cocaine reinforcement in adulthood

Zebra finches are songbirds that learn vocal patterns during a sensitive period of development that approximates adolescence. Exposure of these animals to a cannabinoid agonist during their period of sensorimotor vocal learning alters song patterns produced in adulthood. Thus, songbirds have unique value in studying developmental effects of drug exposure on a naturally learned behavior. A missing feature of this animal model has been a method to study drug reinforcement of behavior. To address this gap we have adapted place conditioning methods, used previously to determine that singing behavior is rewarding, to study cocaine reinforcement of behavior. We have found that cocaine dose-dependently reinforces both place conditioning and aversion at potencies consistent with those observed in mammalian species. Use of this place conditioning method has allowed us to determine that, when administered during periods of sensorimotor vocal learning, delta-9-THC, but not nicotine persistently increases sensitivity to cocaine through adulthood. Establishment of this method significantly expands the songbird drug exposure model, and holds promise for better appreciation of mechanisms important to sensorimotor learning that is dependent upon successful progress through sensitive periods of CNS development.

Repeated cross-fostering affects maternal behavior and olfactory preferences in rat pups.

Disturbances in early mother-infant relationships are strongly associated with changes in the development of a number of physiological and behavioral systems in the neonate that can create a complex change in patterns of vulnerability throughout life. Institutionalized children, despite receiving adequate care, display important behavioral changes in adult life, and such changes are strongly associated with a lack of selective and consistent attachment to the maternal figure in early life. It is not yet clear how human adoption processes alter the mother-infant relationship early in life. Here, to mimic the situation of human adoption and explore the impact on the formation of attachment between the infant and a caregiver, we use a repeated cross-fostering (RCF) model in rodents in two postnatal periods, postnatal days (PND) 1 to 3 (early RCF) and 9 to 11 (late RCF). Early exposure but not late exposure to RCF reduces the pups' preference for the odor of the mother figure. Moreover, early exposure and slightly later exposure to RCF reduce maternal care and motivation in collecting the pups and bringing them to the nest. The RCF protocol creates an unstable environment for mother-pup interaction, but it seems to affect learned attachment to the mother only when it occurs during the corresponding sensitive period of development.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8–13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8–13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8–13, 14–18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8–13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8–13, but lower odds of progressing to the next stage at 14–18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.

Across continents and demographics, unpredictable maternal signals are associated with children's cognitive function

BackgroundEarly life experiences have persisting influence on brain function throughout life. Maternal signals constitute a primary source of early life experiences, and their quantity and quality during sensitive developmental periods exert enduring effects on cognitive function and emotional and social behaviors. Here we examined if, in addition to established qualitative dimensions of maternal behavior during her interactions with her infant and child, patterns of maternal signals may contribute to the maturation of children's executive functions. We focused primarily on effortful control, a potent predictor of mental health outcomes later in life. MethodsIn two independent prospective cohorts in Turku, Finland (N = 135), and Irvine, CA, USA (N = 192) that differed significantly in race/ethnicity and sociodemographic parameters, we assessed whether infant exposure to unpredictable patterns of maternal-derived sensory signals portended poor effortful control. OutcomesIn both the Irvine and Turku cohorts, unpredictable sequences of maternal behavior during infancy were associated with worse effortful control at one year of age. Longitudinal analyses demonstrated that this association persisted for as long as each cohort was assessed-until two years of age in the Turku cohort and to 9.5 years in the Irvine cohort. The relation of unpredictable maternal signals during infancy and the measures of executive function persisted after adjusting for covariates. InterpretationsThe consistency of our findings across two cohorts from different demographic backgrounds substantiated the finding that patterns, and specifically unpredictable sequences, of maternal behaviors may influence the development of executive functions which may be associated with vulnerability to subsequent psychopathology. FundThis research was supported by the National Institutes of Health (NIH) awards P50MH096889, HD051852, NS041298, HD02413, HD050662, HD065823, and by the FinnBrain funders: Academy of Finland (129839, 134950, 253270, 286829, 287908, 308176, 308252), Jane and Aatos Erkko Foundation, Signe and Ane Gyllenberg Foundation, Yrjö Jahnsson Foundation, and State Research Grants (P3498, P3654).

A simple sleep EEG marker in childhood predicts brain myelin 3.5 years later

Epidemiological research reveals that insufficient sleep in children has negative cognitive and emotional consequences; however, the physiological underpinnings of these observations remain understudied. We tested the hypothesis that the topographical distribution of deep sleep slow wave activity during the childhood predicts brain white matter microstructure (myelin) 3.5 y later. Healthy children underwent sleep high-density EEG at baseline (n = 13; ages 2.4–8.0 y) and follow-up (n = 14; ages 5.5–12.2 y). At follow-up, myelin (myelin water fraction) and cortical morphology were also quantified. Our investigation revealed 3 main findings. (1) The Frontal/Occipital (F/O)-ratio at baseline strongly predicted whole brain myelin at follow-up. (2) At follow-up, the F/O-ratio was only minimally (negatively) linked to brain myelin. (3) Cortical morphology was not related to the F/O-ratio, neither at baseline nor at follow-up. Our results support the hypothesis that during child development EEG markers during sleep longitudinally predict brain myelin content. Data extend previous findings reporting a link between EEG markers of sleep need and cortical morphology, by supporting the hypothesis that sleep is a necessary component to underlying processes of brain, and specifically myelin, maturation. In line with the overarching theory that sleep contributes to neurodevelopmental processes, it remains to be investigated whether chronic sleep loss negatively affects white matter myelin microstructure growth during sensitive periods of development.

Case sensitive: Why we should work to identify sensitive developmental periods in PsychoNeuroImmunology

Case sensitive: Why we should work to identify sensitive developmental periods in PsychoNeuroImmunology

Time-Dependent Effects of Exposure to Physical and Sexual Violence on Psychopathology Symptoms in Late Childhood: In Search of Sensitive Periods in Development

Exposure to interpersonal violence is a known risk factor for psychopathology. However, it is unclear whether there are sensitive periods when exposure is most deleterious. We aimed to determine whether there were time periods when physical or sexual violence exposure was associated with greater child psychopathology. This study (N= 4,580) was embedded in Generation R, a population-based prospective birth cohort. Timing of violence exposure, reported through maternal reports (child age, 10 years) was categorized by age at first exposure, defined as: very early (0-3 years), early (4-5 years), middle (6-7 years), and late (8+ years) childhood. Using Poisson regression, we assessed the association between timing of first exposure and levels of internalizing and externalizing symptoms, using the Child Behavior Checklist at age 10 years. Violence exposure at any age was associated with higher internalizing (physical violence: risk ratio [RR]= 1.46, p< 0.0001; sexual violence: RR= 1.30, p< .0001) and externalizing symptoms (physical violence: RR= 1.52, p< 0.0001; sexual violence: RR= 1.31, p= 0.0005). However, the effects of violence were time dependent: compared to children exposed at older ages, children first exposed during very early childhood had greater externalizing symptoms. Sensitivity analyses suggested that these time-based differences emerged slowly across ages 1.5, 3, 6, and 10 years, showing a latency between onset of violence exposure and emergence of symptoms, and were unlikely to be explained by co-occurring adversities. Interpersonal violence is harmful to childhood mental health regardless of when it occurs. However, very early childhood may be a particularly sensitive period when exposure results in worse psychopathology outcomes. Results should be replicated in fully prospective designs.

High seizure load during sensitive periods of development leads to broad shifts in ultrasonic vocalization behavior in neonatal male and female C57BL/6J mice

There is increasing evidence that seizures during early development can impact ultrasonic vocalizations (USVs) emitted from neonatal mice. However, most of the effects of early-life seizures have been reported using chemoconvulsants that produce continuous seizures (status epilepticus). In the present study, we evaluated the impact of different seizure frequency loads during early-life vocalization development in C57BL/6J male and female mice. For the high seizure load (HSL) paradigm, we administered 3 flurothyl seizures to mice on postnatal day (PD) 7 through PD11, and recorded USVs on PD12. We found that the induction of seizures across PD7–11 resulted in increased average duration (P < 0.05) and cumulative duration (P < 0.05) of USVs across both sexes. Call-type analyses indicated several call-type changes, including reduced production of complex call-types from males' HSL condition. For the low seizure load (LSL) paradigm, we induced 3 flurothyl seizures only on PD10 and recorded USVs on PD12. We found no change in any spectral or temporal features of USVs. However, call-type production analyses indicated that both male and female animals from the LSL paradigm also produced changes in call-types. This study provides evidence that the magnitude of communication impairment following seizures is significantly impacted by seizure frequency load early in development.

Reforming and developing socialization of children with limited abilities (mild intellectual disability)

Objectives:The article contains the results of the study of the impact of additional physical education and sports activities on the correction of psycho-physiological disorders, physical qualities of children with intellectual disability. The objectives of the study were the following: 1) to analyze the indicators of the physiological qualities of schoolchildren aged 7–11 with mild intellectual disability; 2) to design a program of additional physical education and sports activities for students of a special (remedial) school of the VIII type on the basis of the study results; 3) to try out the developed program for students of a special (remedial) school of the VIII type.Materials:The longitudinal study (2015-2019) served as the method. The systematic pedagogical monitoring of the state and dynamics of the physiological states of students achieved by them in the course of a school year. The results obtained in the study, processed according to the mathematical method of descriptive statistics and checked with Student’s t-test, the analysis of variance with Fisher’s criterion (F-criterion).Results:In our study, we obtained results that show that the improvement of the motor function in children of primary school age is closely related to the level of morpho-functional maturation of the body and external stimulation with physical exercises. The skillful application of specially selected and dosed physical exercises during the enhanced natural morpho-functional development of the body of children contributes to the improvement of the relevant processes, a significant improvement in the functional capabilities of all body systems.Conclusions:The designed program for students of the special (remedial) school of the VIII type confirmed its effectiveness during the testing. The physiological development program was built on game techniques taking account of the developmental characteristics of children with a mild degree of intellectual disability and positive results were obtained that prove the following: if the physical education program is aimed at developing qualities that correspond to the enhanced natural morpho-functional development of the body of children, it stimulates the accelerated development of the motor function, increasing the adaptive capacity of the child’s body. Additional physical education and sports activities with children who have intellectual disability should be systematic, continuous and they should be organized in such a way that learning the material in the educational and training process could take place in view of the individual state and the sensitive period of development of motor skills.

Sex and Estrous Cycle Effects on Anxiety- and Depression-Related Phenotypes in a Two-Hit Developmental Stress Model.

Stress during sensitive developmental periods can adversely affect physical and psychological development and contribute to later-life mental disorders. In particular, adverse experiences during childhood dramatically increase the risk for the development of depression and anxiety disorders. Although women of reproductive age are twice as likely to develop anxiety and depression than men of the corresponding age, little is known about sex-specific factors that promote or protect against the development of psychopathology. To examine potential developmental mechanisms driving sex disparity in risk for anxiety and depression, we established a two-hit developmental stress model including maternal separation in early life followed by social isolation in adolescence. Our study shows complex interactions between early-life and adolescent stress, between stress and sex, and between stress and female estrogen status in shaping behavioral phenotypes of adult animals. In general, increased locomotor activity and body weight reduction were the only two phenotypes where two stressors showed synergistic activity. In terms of anxiety- and depression-related phenotypes, single exposure to early-life stress had the most significant impact and was female-specific. We show that early-life stress disrupts the protective role of estrogen in females, and promotes female vulnerability to anxiety- and depression-related phenotypes associated with the low-estrogenic state. We found plausible transcriptional and epigenetic alterations in psychiatric risk genes, Nr3c1 and Cacna1c, that likely contributed to the stress-induced behavioral effects. In addition, two general transcriptional regulators, Egr1 and Dnmt1, were found to be dysregulated in maternally-separated females and in animals exposed to both stressors, respectively, providing insights into possible transcriptional mechanisms that underlie behavioral phenotypes. Our findings provide a novel insight into developmental risk factors and biological mechanisms driving sex differences in depression and anxiety disorders, facilitating the search for more effective, sex-specific treatments for these disorders.

Is there a positive side to sensation seeking? Trajectories of sensation seeking and impulsivity may have unique outcomes in young adulthood

IntroductionHigh levels of sensation seeking and impulsivity in adolescence are typically associated with risky behaviours; limited research has examined the relation of these traits to positive outcomes. Given that adolescence is a sensitive developmental period that can impact success later in life, we adopt the Positive Youth Development Framework to better understand how the development of self-reported sensation seeking and impulsivity may be differentially related to positive markers of early adulthood. MethodData are from the Victoria Healthy Youth Survey (T1 N = 662; 52% female), a six-wave longitudinal cohort study of Canadian youth. Parallel process latent class growth analysis estimated trajectories of sensation seeking and impulsivity identifying classes of youth (ages 14–28). Controlling for baseline age, sex, and socio-economic status, linear regression analyses examined how longitudinal patterns (classes) of sensation seeking and impulsivity were related to positive markers of early adulthood. ResultsThree classes of youth were identified. These varied in levels and trajectories of change in sensation seeking (Ss) and impulsivity (I): LowSs-LowI, 26%; HighSs-HighI, 35%; ModerateSs-LowI, 38%. In young adulthood (T6; ages 22–29), youth in the LowSs-LowI and ModerateSs-LowI classes had significantly higher educational and occupational achievement, and lower financial strain, compared to youth in the HighSs-HighI class. Further, the ModerateSs-LowI class was associated with the highest levels of income and well-being. ConclusionsFindings identified differential trajectories of sensation seeking and impulsivity, with youth in the ModerateSs-LowI class, followed by the LowSs-LowI class, reporting the most positive outcomes in young adulthood.

Behavioral effects of postnatal ketamine exposure in rhesus macaque infants are dependent on MAOA-LPR genotype.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles in prenatal and early postnatal neural development, and since previous work suggests ketamine can inhibit monoamine transporters, we hypothesized that there would be behavioral consequences of prenatal and early postnatal exposure to ketamine moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. From a large sample of animals (N=408), we compared groups of rhesus monkeys that had experienced a single exposure to ketamine during prenatal development, an exposure during prenatal development and one postnatal exposure, a postnatal exposure with no prenatal exposure, and no exposures. Animals were classified by putative activity levels for the MAOA genotype and were tested between 3 and 4 months of age on a battery of behavioral tests. Results suggested that animals exposed to ketamine postnatally, at a dose typically used for sedative effects that also had the low-activity variant of MAOA performed poorly on a visual memory test compared to animals with the high-activity variant of the MAOA gene.

Treatment with the glutamate modulator riluzole prevents early life stress-induced cognitive deficits and impairments in synaptic plasticity in APPswe/PS1dE9 mice

BackgroundEnvironmental factors like stress affect age-related cognitive deficits and promote Alzheimer's disease (AD)-related pathology in mice. Excess glutamate has been proposed as a possible mediator underlying these effects in the hippocampus, a vulnerable brain region implicated in learning and memory. MethodsHere, we examined a) whether stress applied during a sensitive developmental period early in life affects later synaptic plasticity, learning and memory and plaque load in the APPswe/PS1dE9 mouse model for Alzheimer's disease and b) whether these effects could be rescued using long-term treatment with the glutamate modulator riluzole. ResultsOur results demonstrate that ELS impairs synaptic plasticity in 6-month-old mice and increases plaque load in 12-month-old APPswe/PS1dE9 mice, while impairing flexible spatial learning in the Barnes maze at this age. Notably, spatial learning correlated well with hippocampal expression of the transporter EAAT2, which is important for extracellular glutamate uptake. The changes in LTP, plaque load and cognition after ELS were all prevented by riluzole treatment that started from post-weaning. ConclusionThese results suggest that normalising glutamate signalling may be a viable therapeutic strategy for treating vulnerable individuals at risk of developing stress-aggravated AD, particularly in relation to adverse early life experiences.

Early lead exposure and pubertal development in a Mexico City population

BackgroundPrevious studies have examined the association between blood lead levels and pubertal timing in adolescent girls; however, the evidence is lacking on the role of lead exposure during sensitive developmental periods on sexual maturation. ObjectivesTo examine the association of prenatal and early childhood lead exposure with pubertal stages among 264 boys and 283 girls aged 9.8–18.0 years in Mexico City. MethodsWe measured maternal bone lead (a proxy for cumulative fetal exposure to lead from maternal bone stores mobilized during pregnancy) at 1 month postpartum. Blood lead was measured annually from 1 to 4 years. Pubertal stage was assessed by a pediatrician. We examined the association between lead and pubertal stages of breast, pubic hair and genitalia using ordinal regression. Age at menarche was evaluated using Cox proportional-hazard models. ResultsMultivariate models showed that maternal patella lead and early childhood blood lead were inversely associated with breast growth (patella OR = 0.72, 95% CI: 0.51–1.00; blood OR = 0.70, 95% CI: 0.53–0.93) in girls. Girls with maternal patella lead in the 3rd tertile and child blood lead in the 2nd tertile had a later age at menarche compared with girls in the 1st tertile (patella HR = 0.60, 95% CI: 0.41–0.88; blood HR = 0.65, 95% CI 0.46–0.91). Additionally, early childhood blood lead was negatively associated with pubic hair growth (OR = 0.68, 95% CI: 0.51–0.90) in girls. No associations were found in boys. ConclusionsThese data suggest that higher prenatal and early childhood exposure to lead may be associated with delayed pubertal development in girls but not boys. Our findings are consistent with previous analyses and reinforce the reproductive effects of lead for girls.

FEATURES OF LENDING YOUTH TOURISM IN UKRAINE

FEATURES OF LENDING YOUTH TOURISM IN UKRAINE

Applications of Developmental Psychopathology.

Developmental psychopathology studies the basic mechanisms, including not only biological factors but also environmental and social factors that may interact with them, by means of which developmental pathways deviate toward pathological or typical outcomes. Family studies conducted during the last century show substantial evidence of heritability among psychiatric disorders. Besides, a large number of genes implicated in shaping the development of the central nervous system have been related to psychiatric conditions. In addition, there is a wide range of stressors and harmful agents that, when acting on sensitive developmental periods, might damage brain function and generate or precipitate psychopathology over time. All these factors have the potential to change the way disorders with a neurodevelopmental origin are expressed, including their age of appearance and clinical manifestations. Both symptoms and social impairment need to be considered in clinical evaluations, as treatment is unlikely to be effective if the problem has not been characterized correctly or if the patients' particular characteristics, which change throughout development, are not taken into consideration.