The Familial Clustering of Age at Menarche in Extended Twin Families

The timing of puberty is complex, possibly involving many genetic factors that may interact with environmental influences. Familial resemblance for age at menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946 mothers and 635 female spouses of male twins. They had indicated their age at menarche as part of a larger longitudinal survey. We assessed assortative mating for age at menarche, gene–environment interaction effects and estimated the heritability of individual differences in pubertal timing. There was significant evidence of gene–environment interaction, accounting for 1.5% of the variance. There was no indication of consistent mate assortment on age at menarche. Individual differences in age at menarche are highly heritable, with additive genetic factors explaining at least 70% of the true variation. An additional 1.5% of the variation can be explained by a genotype–environment interaction effect where environmental factors are more important in individuals genetically predisposed for late menarche

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Effects of the social environment during adolescence on the development of social behaviour, hormones and morphology in male zebra finches (Taeniopygia guttata)

Abstract Background Individual differences in behaviour are widespread in the animal kingdom and often influenced by the size or composition of the social group during early development. In many vertebrates the effects of social interactions early in life on adult behaviour are mediated by changes in maturation and physiology. Specifically, increases in androgens and glucocorticoids in response to social stimulation seem to play a prominent role in shaping behaviour during development. In addition to the prenatal and early postnatal phase, adolescence has more recently been identified as an important period during which adult behaviour and physiology are shaped by the social environment, which so far has been studied mostly in mammals. We raised zebra finches ( Taeniopygia guttata ) under three environmental conditions differing in social complexity during adolescence\ua0-\ua0juvenile pairs, juvenile groups, and mixed-age groups - and studied males\u2019 behavioural, endocrine, and morphological maturation, and later their adult behaviour. Results As expected, group-housed males exhibited higher frequencies of social interactions. Group housing also enhanced song during adolescence, plumage development, and the frequency and intensity of adult courtship and aggression. Some traits, however, were affected more in juvenile groups and others in mixed-age groups. Furthermore, a testosterone peak during late adolescence was suppressed in groups with adults. In contrast, corticosterone concentrations did not differ between rearing environments. Unexpectedly, adult courtship in a test situation was lowest in pair-reared males and aggression depended upon the treatment of the opponent with highest rates shown by group-reared males towards pair-reared males. This contrasts with previous findings, possibly due to differences in photoperiod and the acoustic environment. Conclusion Our results support the idea that effects of the adolescent social environment on adult behaviour in vertebrates are mediated by changes in social interactions affecting behavioural and morphological maturation. We found no evidence that long-lasting differences in behaviour reflect testosterone or corticosterone levels during adolescence, although differences between juvenile and mixed-age groups suggest that testosterone and song behaviour during late adolescence may be associated

Scents of Adolescence: The Maturation of the Olfactory Phenotype in a Free-Ranging Mammal

Olfaction is an important sensory modality for mate recognition in many mammal species. Odorants provide information about the health status, genotype, dominance status and/or reproductive status. How and when odor profiles change during sexual maturation is, however often unclear, particularly in free-ranging mammals. Here, we investigated whether the wing sac odorant of male greater sac-winged bats (Saccopteryx bilineata, Emballonuridae) differs between young and adults, and thus offers information about sexual maturity to potential mating partners. Using gas chromatography – mass spectrometry, we found differences in the odorants of young and adult males prior and during, but not after the mating period. The wing sac odorant of adult males consists of several substances, such as Pyrocoll, 2,6,10-trimethyl-3-oxo-6,10-dodecadienolide, and a so far unidentified substance; all being absent in the odor profiles of juveniles prior to the mating season. During the mating season, these substances are present in most of the juvenile odorants, but still at lower quantities compared to the wing sac odorants of adults. These results suggest that the wing sac odorant of males encodes information about age and/or sexual maturity. Although female S. bilineata start to reproduce at the age of half a year, most males of the same age postpone the sexual maturation of their olfactory phenotype until after the first mating season

Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis

Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia

<p>Abstract</p> <p>Background</p> <p>Many critical maturational processes take place in the human brain during postnatal development. In particular, the prefrontal cortex does not reach maturation until late adolescence and this stage is associated with substantial white matter volume increases. Patients with schizophrenia and other major psychiatric disorders tend to first present with overt symptoms during late adolescence/early adulthood and it has been proposed that this developmental stage represents a "window of vulnerability".</p> <p>Methods</p> <p>In this study we used whole genome microarrays to measure gene expression in post mortem prefrontal cortex tissue from human individuals ranging in age from 0 to 49 years. To identify genes specifically altered in the late adolescent period, we applied a template matching procedure. Genes were identified which showed a significant correlation to a template showing a peak of expression between ages 15 and 25.</p> <p>Results</p> <p>Approximately 2000 genes displayed an expression pattern that was significantly correlated (positively or negatively) with the template. In the majority of cases, these genes in fact reached a plateau during adolescence with only subtle changes thereafter. These include a number of genes previously associated with schizophrenia including the susceptibility gene neuregulin 1 (NRG1). Functional profiling revealed peak expression in late adolescence for genes associated with energy metabolism and protein and lipid synthesis, together with decreases for genes involved in glutamate and neuropeptide signalling and neuronal development/plasticity. Strikingly, eight myelin-related genes previously found decreased in schizophrenia brain tissue showed a peak in their expression levels in late adolescence, while the single myelin gene reported increased in patients with schizophrenia was decreased in late adolescence.</p> <p>Conclusion</p> <p>The observed changes imply that molecular mechanisms critical for adolescent brain development are disturbed in schizophrenia patients.</p

Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders

Cellular composition characterizing postnatal development and maturation of the mouse brain and spinal cord

The process of development, maturation, and regression in the central nervous system (CNS) are genetically programmed and influenced by environment. Hitherto, most research efforts have focused on either the early development of the CNS or the late changes associated with aging, whereas an important period corresponding to adolescence has been overlooked. In this study, we searched for age-dependent changes in the number of cells that compose the CNS (divided into isocortex, hippocampus, olfactory bulb, cerebellum, ‘rest of the brain’, and spinal cord) and the pituitary gland in 4–40-week-old C57BL6 mice, using the isotropic fractionator method in combination with neuronal nuclear protein as a marker for neuronal cells. We found that all CNS structures, except for the isocortex, increased in mass in the period of 4–15 weeks. Over the same period, the absolute number of neurons significantly increased in the olfactory bulb and cerebellum while non-neuronal cell numbers increased in the ‘rest of the brain’ and isocortex. Along with the gain in body length and weight, the pituitary gland also increased in mass and cell number, the latter correlating well with changes of the brain and spinal cord mass. The majority of the age-dependent alterations (e.g., somatic parameters, relative brain mass, number of pituitary cells, and cellular composition of the cerebellum, isocortex, rest of the brain, and spinal cord) occur rapidly between the 4th and 11th postnatal weeks. This period includes murine adolescence, underscoring the significance of this stage in the postnatal development of the mouse CNS

Deficient maternal care resulting from immunological stress during pregnancy is associated with a sex-dependent enhancement of conditioned fear in the offspring

Activation of maternal stress response systems during pregnancy has been associated with altered postpartum maternal care and subsequent abnormalities in the offspring’s brain and behavioral development. It remains unknown, however, whether similar effects may be induced by exposure to immunological stress during pregnancy. The present study was designed to address this issue in a mouse model of prenatal immune activation by the viral mimic polyriboinosinic–polyribocytidilic acid (PolyI:C). Pregnant mice were exposed to PolyI:C-induced immune challenge or sham treatment, and offspring born to PolyI:C- and sham-treated dams were simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. We evaluated the effects of the maternal immunological manipulation on postpartum maternal behavior, and we assessed the prenatal and postnatal maternal influences on anxiety- and fear-related behavior in the offspring at the peri-adolescent and adult stage of development. We found that PolyI:C treatment during pregnancy led to changes in postpartum maternal behavior in the form of reduced pup licking/grooming and increased nest building activity. Furthermore, the adoption of neonates by surrogate rearing mothers, which had experienced PolyI:C-induced immunological stress during pregnancy, led to enhanced conditioned fear in the peri-adolescent and adult offspring, an effect that was exclusively seen in female but not male subjects. Unconditioned (innate) anxiety-related behavior as assessed in the elevated plus maze and open field explorations tests were not affected by the prenatal and postnatal manipulations. Our results thus highlight that being raised by gestationally immune-challenged surrogate mothers increases the vulnerability for specific forms of fear-related behavioral pathology in later life, and that this association may be mediated by deficits in postpartum maternal care. This may have important implications for the identification and characterization of early-life risk factors involved in the developmental etiology of fear-related neuropsychiatric disorders