Characterizing the postnatal hypothalamic-pituitary-adrenal axis response of in utero heat stressed pigs at 10 and 15 weeks of age.

In utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic-pituitary-adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic-pituitary-adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.

Maternal stress, placental 11ß-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways.

INTRODUCTION: Prenatal stress is known to influence fetal hypothalamic-pituitary-adrenal axis (HPA axis) development. Placental 11ß-hydroxysteroid dehydrogenase type 2 (HSD11B2) is a central gene in this pathway, but little is known about what influences its functioning. We assess how maternal distress influences HSD11B2 functioning, and how HSD11B2 in turn, is associated with infant HPA axis development. METHODS: Data come from 24 mother-infant dyads on the Galápagos Islands. Using adjusted linear regression models, we assess the effects of maternal psychosocial (stress and depressive symptoms, measured by the Perceived Stress Scale and the Patient Health Questionnaire-8, respectively) and physiological (HPA axis dysregulation) distress during pregnancy on HSD11B2 methylation and expression and then test how these HSD11B2 measures influence infant HPA axis development. RESULTS: Maternal HPA axis dysregulation during pregnancy is associated with lower placental HSD11B2 expression, which is associated with an exaggerated cortisol reactivity in infants. Sex-specific analyses revealed that maternal depressive symptoms may influence the functioning of placental HSD11B2 differently in girls (n = 11, 46%) than in boys (n = 13, 54%), though the sample size was small. DISCUSSION: These results support a disrupted adaptive framework, in which the ability to upregulate HSD11B2 expression in response to acute stress diminishes as maternal stress becomes chronic. In this model, chronic stress may exhaust the protective mechanism of HSD11B2, leaving the infant vulnerable to high levels of maternal cortisol, which could injure the fetal HPA axis and disrupt long-term neurobehavioral and metabolic development. While larger studies will be needed to confirm these findings, this study offers exploratory results on the effects of maternal distress on both HSD11B2 methylation and expression and the effect of HSD11B2 on offspring HPA axis development.

The Development of Adolescent Chronic Pain following Traumatic Brain Injury and Surgery: The Role of Diet and Early Life Stress.

Pain is evolutionarily necessary for survival in that it reduces tissue damage by signaling the body to respond to a harmful stimulus. However, in many circumstances, acute pain becomes chronic, and this is often dysfunctional. Adolescent chronic pain is a growing epidemic with an unknown etiology and limited effective treatment options. Given that the relationship between acute pain and chronic pain is not straightforward, there is a need to better understand the factors that contribute to the chronification of pain. Since early life factors are critical to a variety of outcomes in the developmental and adolescent periods, they pose promise as potential mechanisms that may underlie the transition from acute to chronic pain. This review examines two early life factors: poor diet and adverse childhood experiences (ACEs); they may increase susceptibility to the development of chronic pain following surgical procedures or traumatic brain injury (TBI). Beyond their high prevalence, surgical procedures and TBI are ideal models to prospectively understand mechanisms underlying the transition from acute to chronic pain. Common themes that emerged from the examination of poor diet and ACEs as mechanisms underlying this transition included: prolonged inflammation and microglia activation leading to sensitization of the pain system, and stress-induced alterations to hypothalamic-pituitary-adrenal axis function, where cortisol is likely playing a role in the development of chronic pain. These areas provide promising targets for interventions, the development of diagnostic biomarkers, and suggest that biological treatment strategies should focus on regulating the neuroinflammatory and stress responses in an effort to modulate and prevent the development of chronic pain.

Early experience alters developmental trajectory of central oxytocin systems involved in hypothalamic-pituitary-adrenal axis regulation in Long-Evans rats.

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored. We use a limited bedding and nesting (LBN) material paradigm as an environmental disruption of early experiences and assessed central oxytocin systems in brain regions related to hypothalamic-pituitary-adrenal (HPA) axis regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus). We also assessed developmentally-appropriate social behaviors and HPA reactivity during social buffering testing in adulthood. LBN litters had larger huddles and more pups visible compared to control litters during the first two weeks of life. LBN also altered the developmental trajectory of oxytocin-expressing cells and oxytocin receptor cells, with increases in oxytocin receptor cells at P15 in LBN pups. By adulthood, LBN females had more and LBN males had fewer oxytocin and oxytocin receptor cells in these areas compared to sex-matched controls. Adult LBN females, but not LBN males, had behavioral changes during social interaction and social buffering testing. The sex-specific effects of early experience on central oxytocin systems and social behavior may contribute to female resilience to early life adversity.

The development of the hypothalamus-pituitary-adrenal axis during infancy may be affected by antenatal glucocorticoid therapy.

BACKGROUND: Developmental changes in the hypothalamus-pituitary-adrenal (HPA) axis during infancy have been reported in term infants, but those in preterm infants have yet to be elucidated. If developmental changes in the HPA axis of preterm infants are modulated by any factors, it may affect their future health. Few studies have examined the lasting consequences of antenatal glucocorticoids on the development of the HPA axis. METHODS: We measured pre- and post-palivizumab vaccination salivary cortisol values in two conforming periods of three-months intervals during infancy, and compared cortisol values and the response of cortisol secretion between groups with and without antenatal glucocorticoid (AG) therapy. RESULTS: Although the strength of the response of cortisol secretion to palivizumab fell age-dependently (until late infancy) in the Non-AG group, the opposite pattern was exhibited in the AG group. The changes of the delta cortisol values between the 2 groups were significant. CONCLUSIONS: This study suggests that the HPA axis of preterm infants whose mothers receive AG therapy may be upregulated during infancy, possibly leading to long lasting health problems.

Biphasic Glucocorticoid Rhythm in One-Month-Old Infants: Reflection of a Developing HPA-Axis?

CONTEXT: The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. OBJECTIVE: To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. DESIGN: Observational. SETTING: Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. PARTICIPANTS: Fifty-five mother-infant pairs. INTERVENTIONS: Collection of breast milk and infants' saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography- tandem mass spectrometry. MAIN OUTCOME MEASURE: GC rhythm in infants' saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses. RESULTS: A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants' GC rhythm. Breast milk cortisol maximum was positively associated with infants' cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am. CONCLUSIONS: A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants' GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.

Developmental influences on stress response systems: Implications for psychopathology vulnerability in adolescence.

The adolescent transition is marked by increases in stress exposure and significant maturation of neural and hormonal stress processing systems. Variability in the development of these systems during adolescence may influence the risk for stress-related psychopathology. This paper aims to review the developmental maturation of the HPA axis and related stress regulation systems, and demonstrate how interference in this adaptive developmental process may increase the risk for negative outcomes. We argue that the developmental maturation of the HPA axis aims to improve the regulatory capacity of the axis in order to more adaptively respond to these increases in stress reactivity. Additionally, we review evidence that sex differences in the development of the HPA and related axes may contribute to sex differences in the risk for stress-related psychopathology. Finally, we discuss how contextual factors, such as early trauma and obesity may alter the development of HPA axis during the adolescence transition and how alterations of normative development increase the risk for stress-related disorders.

Role of corticosterone in anxiety- and depressive-like behavior and HPA regulation following prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) is known to cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperresponsivity to stressors. Dysregulation of the HPA axis plays a role in vulnerability to stress-related disorders, such as anxiety and depression. Thus, the effects of PAE on HPA function may result in increased vulnerability to the effects of stress and, in turn, lead to the development of stress-related disorders. Indeed, individuals prenatally exposed to alcohol have an increased risk of developing anxiety and depression. However, it is unclear whether hypersecretion of corticosterone (CORT) in response to stress per se is involved with mediating differential effects of stress in PAE and control animals. To investigate the role of CORT in mediating effects of stress in both adult females and males following PAE, adrenalectomy with CORT replacement (ADXR) was utilized to produce similar CORT levels among prenatal treatment groups before exposure to chronic unpredictable stress (CUS). Anxiety-like behavior was evaluated using the open field and elevated plus maze, and depressive-like behavior was examined in the forced swim test. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression was assessed in the medial prefrontal cortex (mPFC), amygdala, and hippocampal formation. Under the non-CUS condition, PAE alone differentially altered anxiety-like behavior in sham but not ADXR females and males, with females showing decreased anxiety-like behavior but males exhibiting increased anxiety-like behavior compared to their control counterparts. There were no effects of PAE alone on depressive-like in females or males. PAE also decreased GR mRNA expression in the hippocampal formation in females but had no effects on MR or GR mRNA expression in any brain region in males. CUS had differential effects on anxiety- and depressive-like behavior in PAE and control animals, and these effects were sex dependent. Importantly, ADXR unmasked differences between PAE and control animals, demonstrating that CORT may play a differential role in modulating behavior and HPA activity/regulation in PAE and control animals, and may do so in a sex-dependent manner.

Childhood maltreatment, pituitary volume and adolescent hypothalamic-pituitary-adrenal axis - Evidence for a maltreatment-related attenuation.

BACKGROUND: Alterations of the development of the hypothalamic-pituitary-adrenal axis (HPAA) have been suggested to be related to experiences of early maltreatment. It has been postulated that early stress (i.e., maltreatment) leads to initial hyperactivation of the HPAA, which subsequently may progress to hypoactivation during the course of adolescence, however empirical studies on this hypothesis are rare. In the current study, we aimed to examine the longitudinal relationships between childhood maltreatment, early adolescent pituitary gland volume (PGV) and mid-adolescent cortisol output in an existing data set to explore the utility of PGV as a measure of HPAA function, and as an indirect test of the attenuation hypothesis. METHODS: The sample comprised 69 adolescents (30 females), subsampled from a larger longitudinal, community-based study on adolescent development. PGV, as an estimate of chronic childhood HPAA activity, was measured by magnetic resonance imaging during early adolescence (mean age 12.62 ± 0.45 years). Cortisol output was assessed via multiple salivary cortisol measures in mid-adolescence (mean age 15.52 ± 0.39 years). The cortisol awakening response (CAR) was calculated as a measure of HPAA functioning. Retrospective assessment of childhood maltreatment was performed using the Childhood Trauma Questionnaire (CTQ). Regression analyses were conducted to examine whether childhood maltreatment, PGV, and their interaction, predicted mid-adolescent CAR. RESULTS: No main effect of PGV or maltreatment was found on adolescent CAR. PGV did however significantly interact with childhood maltreatment in predicting the CAR (t = -2.26; p = 0.024). Larger PGV positively predicted lower CAR in the context of relatively high childhood maltreatment (t = 2.032; p = 0.046), but showed no relationship in the context of relatively low maltreatment (t = 0.723; p = 0.472). Maltreatment also interacted with sex, such that (only) in females, higher levels of maltreatment predicted a lower CAR (t = -2.04, p = 0.042). CONCLUSIONS: In the presence of childhood maltreatment, larger PGV was associated with lower CAR in adolescence, providing support for the application of PGV in studies of HPA axis function. Our finding is consistent with a maltreatment-related attenuation of HPAA functioning that may derive from a stress induced chronic hyperactivation during childhood. Prospective longitudinal studies are now required to further explicate these findings and relationships with psychopathology.

Diurnal Cortisol Concentrations and Growth Indexes of 12- to 48-Month-Old Children From Mexico City.

Context: Early life cortisol plays an important role in bone, muscle, and fat mobilization processes, which could influence body composition, affecting anthropometric indicators such as weight and height. Objective: To explore the association between diurnal cortisol levels and growth indexes in children from 12 to 48 months of age. Design: This study includes data from 404 children from the Programming Research in Obesity, Growth, Environment and Social Stressors Mexican birth cohort. Cortisol was measured in eight saliva samples collected at four time points during the day (from wakeup to bedtime), over 2 days, when the child was either 12, 18, or 24 months old. Total daytime cortisol levels were calculated by averaging the area under the curve (AUC) for the 2 days. Height and weight were measured from 12 to 48 months of age. Growth indexes were constructed according to z scores following World Health Organization standards: weight-for-age z score (Z-WFA), height/length-for-age z score, weight-for-height/length z score (Z-WFH), and body mass index-for-age z score (Z-BMIFA). Mixed models were used to analyze the association between cortisol AUC quartiles and growth indexes. Results: Cortisol showed an inverted U-shaped association with the four growth indexes. Compared with the first quartile, all quartiles had a positive association with indexes that include weight, with the second quartile having the strongest association, resulting in an average change of ß (95% CI) 0.38 (0.13-0.64) for Z-WFA, 0.36 (0.10-0.62) for Z-WFH, and 0.43 (0.17-0.69) for Z-BMIFA. Conclusions: Results suggest that early life daytime cortisol levels, as a reflection of hypothalamic-pituitary-adrenal axis development, might influence growth in early infancy.

Stress, alcohol and infection during early development: A brief review of common outcomes and mechanisms.

Although stress is an adaptive physiological response to deal with adverse conditions, its occurrence during the early stages of life, such as infancy or adolescence, can induce adaptations in multiple physiological systems, including the reproductive axis, the hypothalamic-pituitary-adrenal (HPA) axis, the limbic cortex and the immune system. These early changes have consequences in adult life, as seen in the physiological and behavioural responses to stress. This review highlights the impact of several stress challenges incurred at various stages of development (perinatal, juvenile, adolescent periods) and how the developmental timing of early-life stress confers unique physiological adaptations that may persist across the lifespan. In doing so, we emphasise how intrinsic sex differences in the stress response might contribute to sex-specific vulnerabilities, the molecular processes underlying stress in the adult, and potential therapeutic interventions to mitigate the effects of early stage stress, including the novel molecular mechanism of SUMOylation as a possible key target of HPA regulation during early-life stress.

Developmental Lead Exposure and Prenatal Stress Result in Sex-Specific Reprograming of Adult Stress Physiology and Epigenetic Profiles in Brain.

Developmental exposure to lead (Pb) and prenatal stress (PS) both impair cognition, which could derive from their joint targeting of the hypothalamic-pituitary-adrenal axis and the brain mesocorticolimbic (MESO) system, including frontal cortex (FC) and hippocampus (HIPP). Glucocorticoids modulate both FC and HIPP function and associated mediation of cognitive and other behavioral functions. This study sought to determine whether developmental Pb ± PS exposures altered glucocorticoid-related epigenetic profiles in brain MESO regions in offspring of female mice exposed to 0 or 100 ppm Pb acetate drinking water from 2 mos prior to breeding until weaning, with half further exposed to prenatal restraint stress from gestational day 11-18. Overall, changes in females occured in response to Pb exposure. In males, however, Pb-induced neurotoxicity was modulated by PS. Changes in serum corticosterone levels were seen in males, while glucocorticoid receptor changes were seen in both sexes. In contrast, both Pb and PS broadly impacted brain DNA methyltransferases and binding proteins, particularly DNMT1, DNMT3a and methyl-CpG-binding protein 2, with patterns that differed by sex and brain regions. Specifically, in males, effects on FC epigenetic modifiers were primarily influenced by Pb, whereas extensive changes in HIPP were produced by PS. In females, Pb exposure and not PS primarily altered epigenetic modifiers in both FC and HIPP. Collectively, these findings indicate that epigenetic mechanisms may underlie associated neurotoxicity of Pb and of PS, particularly associated cognitive deficits. However, mechanisms by which this may occur will be different in males versus females.

The impact of adolescent stress experiences on neurobiological development.

Adolescence is considered a developmental period of heightened vulnerability to many psychological dysfunctions-primarily due to the high structural neuronal plasticity that accompanies the associated physical and cognitive gains, rendering an individual highly susceptible to environmental stressors during this time. Recently, interest has been generated in the study of neuronal and behavioral adaptation to adverse experiences during adolescence. This review will provide an overview of the principal neurobehavioral changes that occur during adolescence and describe what happens when the maturation of these functions is altered by stressful environmental stimuli.

Two New Insertion/Deletion Variants of the PITX2 Gene and their Effects on Growth Traits in Sheep.

In China, Tong sheep (TS) and Lanzhou fat-tailed sheep (LFTS) are two closely relative endanger breeds for low meat production and low fecundity, finding some marker-assisted selected (MAS) is our first priority for improving their growth traits. For this purpose, Hu sheep (HS) and small-tailed Han sheep (STHS) were compared with two endangered breeds (TS and LFTS). Paired-liked homeodomain transcription factor 2 (PITX2) gene was the important member of PITX family, which could adjust animal growth through hypothalamic-pituitary-adrenal axis. During the past years, insertion/deletion (indel) has become increasingly popular in application as MAS. In this study, two novel indel loci were identified, and five significant differences, including chest width, hip width, chest depth, chest circumference, and body height, were found between different breeds. Interestingly, there was no DD genotype and smaller number of ID genotye. All the ID genotypes were significantly greater than II genotype, which was to say the allele of "D" was dominant variation and its frequency was lower, which demonstrated that it has huge space for selection. Briefly, the two indel were potential and useful DNA markers for selecting excellent individuals in relation to growth traits in sheep.

The link between aberrant hypothalamic-pituitary-adrenal axis activity during development and the emergence of aggression-Animal studies.

Aggressive behavior is not uniform, including proactive and reactive forms of aggression. Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is frequently associated with abnormal aggression. Here, we review the rodent literature in order to assess whether developmental abnormalities in the HPA axis can be causally linked with the emergence of abnormal aggression. We examine studies that involve genetic models and life challenges (e.g., early life stress, drug exposure) that course with developmental alterations in the HPA axis. Although the lack of systematic studies hinders development of an integrated model, existing evidence supports a U-shaped function regarding differences in HPA axis functioning during development and the emergence of aggressive phenotypes. Thus, developmentally low or high HPA axis reactivity are typically found to be aligned with the emergence of aggressive phenotypes; however, existing information is insufficient to causally link divergent HPA axis aberration with specific types of aggression. Progress in this field is needed to support interventions in children aimed at ameliorating social dysfunctions associated with aberrations in HPA axis function.

Early child adversity and psychopathology in adulthood: HPA axis and cognitive dysregulations as potential mechanisms.

Early adversity (EA) has been shown to be a potent risk factor for developing a psychopathology in adulthood. Alterations of the stress system in addition to changes in brain development have been suggested to explain some of the psychopathologies associated with EA. The stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, which leads to the production of glucocorticoids (GCs; cortisol in humans). Being soluble in lipids, GCs easily cross the blood brain barrier and access GC receptors in the hippocampus, prefrontal cortex and amygdala. These three brain structures do not develop at the same rhythm in humans and recent models suggest that exposition to EA at different times throughout cerebral development can induce a differential vulnerability to diverse mental illnesses. Although these models are of interest, they do not provide any mechanism(s) through which exposition to EA could lead to an increased vulnerability to certain mental illnesses and not others. Interestingly, the main brain structures that are affected by the chronic secretion of stress hormones during childhood (hippocampus, prefrontal cortex and amygdala) are differentially involved in various cognitive functions (memory, emotion regulation, encoding of emotional memories, etc.). It is therefore proposed that exposure to EA, by affecting the development of specific brain structures, might alter the underlying cognitive process of these brain regions, and increase vulnerability to specific mental disorders in adulthood.

Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence.

Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70days of age) or adolescent (30days of age) male C57BL/6N mice to 4 weeks of either 0 or 25µg/ml oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected by chronic corticosterone treatment in adult animals, but led to a hyper-responsive PVN in the corticosterone-treated adolescent animals, suggesting an age-specific effect of corticosterone treatment on later PVN stress reactivity. Together, these experiments highlight the influence of developmental stage on somatic and neuroendocrine outcomes following chronic HPA disruption by noninvasive, oral corticosterone treatment. Given the substantial vulnerabilities to HPA dysfunctions during adolescence this model may prove useful in better understanding these vulnerabilities.

[Developmental pattern of hypothalamic-pituitary-adrenal axis during pubertal transition and implications for emotional disorders].

During an individual's life, puberty is not only a crucial phase for physical development, but a key period for neuroendocrine transformation. As a major neuroendocrine axis, the influence of hypothalamic-pituitary-adrenal (HPA) axis's changes during puberty on mental and physical health, as well as emotional symptoms, is causing a growing attention. However, information of its developing pattern and circadian variation is limited. Recent research has demonstrated that certain developing pattern of HPA axis in puberty is closely related to the adolescent emotional disorders, which highlights the recognition of HPA functions developing paths under both resting and stress state and the evaluation of its prediction effect for the adolescent emotional disorders. Generally, cortisol awakening response is utilised to assess HPA functions. Elaborating the variation of HPA axis functions from the puberty to the later developing process provides much guiding significance for the early screening, intervention and treatment of adolescent emotional disorders.

Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans.

Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity. This may be due to changes in placental glucocorticoid metabolism leading to increased fetal glucocorticoid exposure. We discuss the potential consequences of increased vulnerability of the female HPA axis for later life health and consider the underlying mechanisms. Further studies are needed to determine whether sex-differences in early-life programming of the HPA axis represent a pathway underpinning the sex-differences in common cardiometabolic and psychiatric diseases.

Income inequality, gene expression, and brain maturation during adolescence.

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age.