HPA Axis Function Research Articles

Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence

Exposure to prenatal stress (PNS) has the potential to elicit multiple neurobiological alterations and increase the susceptibility to psychiatric disorders. Moreover, gestational stress may sensitize the brain toward an altered response to subsequent challenges. Here, we investigated the effects of PNS in rats and assessed whether these animals exhibit an altered brain responsiveness to an acute stress (AS) during adolescence. From gestational day 14 until delivery, Sprague Dawley dams were exposed to PNS or left undisturbed. During adolescence (PND38 to PND41), offspring were tested in the social interaction and splash test. At PND44 half of the animals were exposed to 5 min of forced swim stress. Males and Females exposed to PNS showed reduced sociability and increased anhedonic-like behavior. At the molecular level, exposure of adolescent rats to AS produced increased activation of the amygdala and ventral and dorsal hippocampus. Regarding the prefrontal cortex (PFC), we observed a pronounced activation in PNS males exposed to AS. Cell-type specific transcriptional analyses revealed a significant imbalance in the activation of PFC excitatory and inhibitory neurons in PNS males and females exposed to AS. Furthermore, stressed males exhibited disrupted HPA-axis function, while females showed impairments in the modulation of antioxidant genes. Our study shows that PNS induces emotional dysregulation and alters the responsiveness of the PFC to an acute stressor. Moreover, the disruption of excitatory and inhibitory balance during adolescence could influence the ability to respond to challenging events that may contribute to precipitate a full-blown pathologic condition.

7085 Myoclonus Seizure with Pseudo-Adrenal Insufficiency as the Clinical Manifestations Leading to the Diagnosed Multi-focal Insulinomas that Mimic Multiple Endocrine Neoplasia Type 1 Syndrome

Abstract Disclosure: P. Kiatpanabhikul: None. Background: Insulinoma is a rare disease that presents with varying symptoms and can be sporadic or associated with hereditary syndromes (1). These rare points of views of insulinoma-patient on clinical manifestations, hormonal responses and surgical pathology result for final diagnosis and management. Clinical Case: A 59-year-old woman presented with myoclonic seizure of right arm with consciousness duration 5-10 minutes every midday twice a week for 6 months and generalized convulsion for 20 minutes ago. She had a low FPG level (59 mg/dL; n 70-100) and was admitted to doing 72-hour fasting test that revealed hypoglycemia at 12-hour of fasting with a nadir glucose level of 55 mg/dL, insulin 3.7 uIU/mL (cutoff > 5), C-peptide 0.4 ng/mL (cutoff > 0.6), cortisol 6.22 mcg/dL (n 5-25) and normal morning ACTH level (29.8 pg/mL; n 10-65). These were appropriated response of endogenous insulinemia with inappropriate response of serum cortisol level in hypoglycemic feature. MRI pituitary gland was considered to evaluate secondary hypocortisolism which showed a small less enhancing lesion left anterior lobe 0.3x0.45-cm without any pituitary hormonal abnormalities that were considered non-functioning pituitary microadenoma which could not explain inappropriate response of cortisol level to hypoglycemic period in this patient. Five months later, she presented at the emergency room with myoclonic seizure on her extremities, blurred consciousness and slurred speech after having lunch for 1-2 hour and revealed CPG 30 mg%, severe hypoglycemia (26 mg/dL), hypocortisolism (4.49 mcg/dL), with endogenous hyperinsulinemia (insulin 55.2 uIU/mL, C-peptide 2.5 ng/mL). 250-mcg ACTH stimulation test was done and showed normal response of her HPA-axis function (serum cortisol level at 0, 30, 60 min was 9.12, 17.87, 18.61 mcg/dL). CT pancreatic protocol showed several arterial enhancing nodules scattering at pancreatic tails isoattenuation to pancreatic parenchyma on portovenous phase up to 1.7*1.6 cm. She was operated on to distal pancreatectomy with intraoperative insulin/glucose ratio monitoring. Surgical pathology confirmed 4-well-differentiated pancreatic neuroendocrine tumors with insulin-producing, sizes 0.5-1.7 cm in diameter. Her final diagnosis was multi-focal insulinomas with non-functioning pituitary microadenoma that mimic MEN-1 syndrome without secondary adrenal insufficiency. She underwent successful surgical resection with complete resolution of symptoms during 4 years of followed-up with no recurrence and no having any hypercalcemia and hyperprolactinemia. Conclusion: Multi-focal insulinomas can be presented as sporadic, more severe hypoglycemia and endogenous hyperinsulinemia during period after meal with myoclonic seizure and pseudo-adrenal insufficiency in older-aged, non-diabetes person without recurrence after treatment for 4-year of followed-up. Presentation: 6/2/2024

Acute stress-induced reductions in neural response to reward are related to acute stress-related increases in cortisol.

Stressors and blunted reward processing are implicated in depression. The current study simultaneously examined the impact of an acute stressor on cortisol and reward processing, measured using the reward positivity (RewP) in 66 participants. Participants completed a reward task during a stressor and a control condition, counterbalanced, and separated by 1 week, while saliva samples were collected before, immediately following, and 25 min after the reward task. Participants reported that the stressor condition was more stressful than the control condition. Cortisol levels did not differ before the reward task; however, cortisol levels were higher both immediately and 25 min after the task. The RewP was blunted during the stressor compared to the control condition, and participants with a larger stress-induced increase in cortisol had greater reductions in their RewP. The current study provides evidence that stress-induced changes in HPA-axis functioning relate to reductions in neural correlates of reward processing.

Effects of brain estrogen receptor on depression and its mechanism of action

Depression is a refractory disease involving multiple pathologic changes, characterized by long-term disease course, low curative rate, and complex symptoms. However, the pathologic mechanism of this disease is incompletely known. Current research mainly focuses on the monoamine neurotransmitter hypothesis, neuroendocrine-related hypothesis, neuroinflammation hypothesis, and brain structure-function hypothesis. An intimate interplay exists between estrogen with the development and progression of depression. Estrogen receptors are widely distributed in the central nervous system, the expression of which can exert genetic and nongenetic effects to improve depression through regulating the level of neurotransmitters, mediating the function of the hypothalamus-pituitarium-adrenal axis, alleviating neuroinflammation, and protecting neurons. This study elaborated on the regulatory effect and mechanism of brain estrogen receptors on depression, hoping to provide new ideas for the clinical treatment of depression.

Hair cortisol and substance use among women currently experiencing intimate partner violence: The role of PTSD symptom severity

IntroductionSubstance use is highly prevalent among women experiencing intimate partner violence (IPV) and has been associated with dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and resulting cortisol response. Posttraumatic stress disorder (PTSD) symptoms may play an important role in exacerbating the association between cortisol levels and substance use behaviors. PurposeThis study examined the role of PTSD symptoms in the relation between cortisol and past month substance use behaviors. The current study used hair cortisol as an index of past 30-day HPA-axis functioning and ecological momentary assessment (EMA) to characterize substance use behaviors more accurately over a 30-day period. MethodParticipants were 90 community women who had experienced physical or sexual IPV in the past 30 days by their current male partner and used any amount of alcohol or drugs (M age = 40.71; 54.4 % white). Participants completed (a) a baseline interview, (b) EMA for 30-days, and (c) a follow up interview where they were asked to provide a hair sample for cortisol analyses. Data collection took place from 2018 to 2020. ResultsPTSD severity moderated the relations between cortisol and days of drinking and binge drinking. In the context of high PTSD symptomology, women with high cortisol levels spent, on average, an additional 7.4 days drinking and 8.1 days binge drinking in the past 30 days compared to women with low cortisol levels, in a model adjusted for age. ConclusionsResults highlight the prominent role of PTSD symptoms in the association between cortisol and alcohol use among women experiencing IPV.

Effects of sensory overstimulation in postpartum rats

Research in rodents has shown that exposure to excessive early life audiovisual stimulation leads to altered anxiety-like behaviors and cognitive deficits. Since this period of stimulation typically begins prior to weaning, newborn rodents receive sensory overstimulation (SOS) as a litter within their home cage while the dam is present. However, the effects of SOS during the postpartum period remain unexplored. To this end, we adapted an SOS paradigm for use in rats and exposed rat dams and their litters from postpartum days (PD) 10-23. Maternal observations were conducted to determine whether SOS produced changes in positive and/or negative maternal behaviors. Next, we assessed changes in anxiety-like behavior and cognition by testing dams in the elevated zero maze, open field, and novel object recognition tests. To assess potential effects on HPA-axis function, levels of the stress hormone corticosterone (CORT) were measured approximately 1-week after the cessation of SOS exposure. Our results indicate increased nursing and licking in SOS dams compared to controls, although SOS dams also exhibited significant increases in pup dragging. Moreover, SOS dams exhibited reduced self-care behaviors and nest-building compared to control dams. No differences were found for anxiety-like behaviors, object recognition memory, or CORT levels. This study is the first to assess the impact of postpartum SOS exposure in rat dams. Our findings suggest an SOS-induced enhancement in positive caregiving, but limited impact in all other measures.

The cortisol/DHEA ratio mediates the association between early life stress and externalizing problems in adolescent boys

BackgroundDespite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations. Methods138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems. ResultsWe found that ELS is associated with both a lower CD ratio and more externalizing problems. Importantly, a lower CD ratio mediated the association between ELS and externalizing problems in boys. ConclusionsAn imbalance in adrenal hormones may be a mechanism through which ELS leads to an increase in externalizing problems in adolescent boys. These findings underscore the utility of using the CD ratio to index HPA-axis functioning.

Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients

BackgroundNeuroinflammation is a hallmark of the Alzheimer’s disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates. Method134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales. ResultHigher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales. ConclusionThis study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.

Prenatal exposure to social adversity and infant cortisol in the first year of life

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman’s reports of social adversity during the third trimester were associated with their infant’s resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants’ cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents

Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13–15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Hair cortisol and dehydroepiandrosterone and their associations with optimism and pessimism in older people

The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some psychological traits such as optimism and pessimism have been shown to be related to both health and the stress response, although their relationship with the HPA axis is inconclusive. More stable HPA axis biomarkers, such as hair samples of cortisol (HC) and dehydroepiandrosterone (HDHEA), would help to clarify the association between these psychological traits and HPA axis functioning. The main aim of this study was to test the relationships between optimism and pessimism and chronic stress biomarkers measured in hair (HC and HDHEA). Additionally, a secondary objective was to explore sex differences in HC and HDHEA levels and their relationship with these psychological traits. We measured optimism, pessimism, and their combination (dispositional optimism) using the Life Orientation Test Revised (LOT-R) and chronic stress biomarkers (HC and HDHEA) in 119 healthy participants (46 men and 73 women) between 56 and 81 years old who belonged to a university program. Regression analyses controlling for perceived stress and BMI indicated that higher dispositional optimism was related to lower HC and HC:HDHEAratio (β = −0.256, p = .008 and β = −0.300, p = .002, respectively). More specifically, higher pessimism was related to higher HC (β = 0.235; p = .012) and HC:HDHEAratio (β = 0.240; p = .011), whereas higher optimism was associated with a lower HC:HDHEAratio(β = −0.205; p = .031). Moderation analyses showed no sex differences. To date, this is the first study to investigate the link between these traits and HC and HDHEA in older people. Our results confirm that positive and negative expectations about the future (i.e. optimism and pessimism) may play an important role in health due to their relationship with the HPA axis. They also strengthen the idea that the negative effects of pessimism have a greater weight than the protective effects of optimism in their relationship with HPA axis regulation.

Gender minority stress and diurnal cortisol profiles among transgender and gender diverse people in the United States

The field of behavioral neuroendocrinology has only begun to explore the lived experiences of transgender and gender diverse (TGD) people exposed to stigma. In light of escalating attacks and legislation targeting TGD people in the United States, it is crucial to examine the physiological pathways through which gender minority stressors become embodied, impact health, and contribute to health inequities. The Trans Resilience and Health Study included baseline data collection from fall 2019 to spring 2020 from a sample of 124 TGD people, reflecting a diversity of gender identities (e.g., trans masculine, trans feminine, and nonbinary) and ages (range = 19–70 years old; M = 34.10), living in Michigan, Nebraska, Oregon, and Tennessee. These analyses examine experiences of gender-related enacted stigma in association with hypothalamic-pituitary-adrenal (HPA)-axis functioning. Among those experiencing the highest levels of enacted stigma, findings show a blunted cortisol awakening response and sluggish daily decline that resulted in elevated concentrations at bedtime compared to those experiencing less enacted stigma. These results of flattened diurnal activity are consistent with an emergent literature on discrimination as a social determinant of potential stress pathophysiology. In contrast, community connectedness was associated with a larger, more dynamic cortisol awakening response. These findings emphasize the importance of incorporating gender-minority stress and resilience measures when studying HPA-axis functioning among TGD people.

Exercise in the Treatment of Repetitive, Self-Injurious, and Aggressive Behavior in Adults with Autism Spectrum Disorder: A Neurobiological Analysis

Objective: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by markedly impaired social interaction and restricted/ repetitive patterns of behavior, interests, and activities. Maladaptive behaviors associated with ASD can include stereotyped, self-injurious, and aggressive behaviors. Current evidence-based interventions for ASD involve specialist availability, financial, time, and side effect constraints. Physical exercise has received increasing attention in the treatment of children with ASD, but research in adults is comparatively scarce. The purpose of this paper is to explore possible mechanisms by which exercise can reduce repetitive, self-injurious, and aggressive behaviors in adults with ASD. Methods: The literature on the neurobiology of exercise is reviewed and compared with the literature on the neurobiology of ASD. Information from this comparison is then used to formulate possible mechanisms by which exercise may reduce maladaptive behaviors in adults with ASD. Results: Plausible mechanisms for an exercise-induced beneficial effect on maladaptive behaviors in adults with ASD include modulation of neurotransmitter release and function, facilitation of endocannabinoid release, increased expression of neurotrophic factors, improved functional connectivity in higher-level cognitive networks, reduced oxidative stress, improved HPA axis function, treatment of comorbid depression, and reduction in amyloid beta deposition in cortical GABAergic neurons and subcortical structures. Conclusions: Future research should attempt to confirm the efficacy of exercise in reducing maladaptive behaviors in adults with ASD as well as the proposed mechanisms for such a relationship. Verification of these issues would have major implications in terms of supporting an evidence-based, inexpensive, widely available, and broadly beneficial treatment for adults with ASD.

Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children

BackgroundThe biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes. MethodsThe participants were 52 children of Mexican or Central American origin aged 11.6–15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood. ResultsOverall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures. ConclusionsAssessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance.

Chronic social defeat stress and glucocorticoid regulation in brain regions: resistance or hypersensitivity?

Chronic social defeat stress and glucocorticoid regulation in brain regions: resistance or hypersensitivity?

Antidepressant-like Effect of Oroxylum indicum Seed Extract in Mice Model of Unpredictable Chronic Mild Stress.

Major depressive disorder (MDD) is one life-threatening disorder that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Currently, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, could have an antidepressive property. An in vitro monoamine oxidase-A (MAO-A) inhibitory assay was used to preliminarily screening for the antidepressant effect of O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks, and the daily administration of OIS extract started from week 4. The mechanisms involved in the antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in the UCMS-induced mouse model via two possible pathways: (i) it normalized the HPA axis function via the restoration of negative feedback (decreased FKBP5 and increased GR expressions) and the reduction in the glucocorticoid-related negative gene (SGK-1), and (ii) it improved neurogenesis via the escalation of BDNF and CREB expressions in the hippocampus and the frontal cortex. In addition, an HPLC analysis of the OIS extract showed the presence of baicalin, baicalein, and chrysin as major constituents. All of the results obtained from this study emphasize the potential of OIS extract containing baicalin and baicalein as an effective and novel alternative treatment for MDD.

Effects of menstrual cycle phase and ovulation on the salivary cortisol awakening response

The cortisol awakening response (CAR) is influenced by several state and trait variables, one of which might be the menstrual cycle in women. Previous results suggested that the CAR is enhanced around ovulation, which is why it has been recommended to avoid sampling during the ovulatory phase. In two separate studies, we aimed to replicate previous findings that reported the CAR’s modulation across the menstrual cycle, especially during ovulation. In Study 1, a group of 27 healthy naturally cycling women collected saliva at 0, 30, 45, and 60 min post-awakening on two days during their follicular, ovulatory, and luteal phases in a repeated measures design. In Study 2, CAR samples were collected from 30 healthy naturally cycling women on seven consecutive days around the expected ovulation. To increase reliability of CAR measurements, participants' compliance of saliva sampling times was monitored, ovarian steroids (estradiol and progesterone) were collected, and ovulation was confirmed with specific test kits. Contrary to our expectations, we detected no differences in the CAR over the menstrual cycle, and no significant association with variations in estradiol and progesterone. In addition, we excluded confounding effects such as compliance and validated the cycle phase. These results suggest that the CAR is largely robust against hormonal variations across the menstrual cycle, including the mid-cycle phase around ovulation. However, further research is needed to understand the potential ovarian steroid-induced modulation of HPA axis functioning and the menstrual cycle’s effects on salivary cortisol levels in psychobiological studies.

Comprehensive assessment of cortisol and cortisol metabolites provides insight into the complex relationship between HPA axis function and BMI

Aims/objectivesAlthough considerable effort, both experimental and theoretical, has been directed towards understanding the relationship between the HPA axis and weight regulation, no true consensus exists in the literature as to the nature of the relationship. The aim of this study was to explore potential correlations between BMI and measures of cortisol and cortisol metabolites using dried urine and saliva sampling in a large sample of individuals with BMIs ranging from underweight to obese. Materials and methodsA cohort of patients with data available from urinary and/or salivary measures of cortisol and cortisol metabolites who met inclusion criteria was extracted from the database of a commercial clinical laboratory. Pearson correlation coefficients were used to determine associations between variables; Student's t-test and one-way ANOVA were used to examine differences between groups, and the Jonckheere-Terpstra trend test was used to assess for trends by BMI category. A multivariable linear regression model was created to determine which variables explained the largest amounts of variance in BMI. ResultsA significant correlation was observed between the urinary cortisol metabolites and BMI (P < 0.0001). In addition, cortisol metabolites were associated with changes in BMI over time. No significant correlation was observed between urinary free cortisol and BMI, and correlations observed between BMI and other variables, with the exception of age, were either weak or not statistically significant. ConclusionsThe data presented in this study suggest that cortisol metabolism is a key component of weight regulation and that cortisol metabolite concentrations may potentially serve as informative biomarkers to characterize the relationship between the HPA axis and changes in BMI. The implications of this affect both clinical practice and the research and development of both prevention and treatment strategies aimed at either decreasing or increasing BMI.

The effects of sleep restriction during abstinence on oxycodone seeking: Sex-dependent moderating effects of behavioral and hypothalamic-pituitary-adrenal axis-related phenotypes

During opioid use and abstinence, sleep disturbances are common and are thought to exacerbate drug craving. In this study, we tested the hypothesis that sleep restriction during abstinence from oxycodone self-administration would increase drug seeking during extinction and footshock reinstatement tests. We also performed behavioral phenotyping to determine if individual variation in responses to stressors and/or pain are associated with oxycodone seeking during abstinence, as stress, pain and sleep disturbance are often co-occurring phenomena. Sleep restriction during abstinence did not have selective effects on oxycodone seeking for either sex in extinction and footshock reinstatement tests. Some phenotypes were associated with drug seeking; these associations differed by sex and type of drug seeking assessment. In female rats, pain-related phenotypes were related to high levels of drug seeking during the initial extinction session. In male rats, lower anxiety-like behavior in the open field was associated with greater drug seeking, although this effect was lost when correcting for oxycodone intake. Adrenal sensitivity prior to oxycodone exposure was positively associated with footshock reinstatement in females. This work identifies sex-dependent relationships between HPA axis function and opioid seeking, indicating that HPA axis function could be a therapeutic target for the treatment of opioid use disorder, with tailored approaches based on sex. Sleep disturbance during abstinence did not appear to be a major contributing factor to opioid seeking.

Association between Hpa Axis Functioning and Mental Health in Maltreated Children and Adolescents: A Systematic Literature Review.

Previous studies have demonstrated that children who experience maltreatment show a more elevated risk of psychopathological disorders than children from the general population. The HPA (hypothalamic-pituitary-adrenal) axis is not mature at birth and undergoes strong social regulation during the first years of life. Consequently, early exposure to stress could modify the usual adaptative response to stress. In stressful situations, perturbations in both cortisol response and cortisol circadian rhythm have been observed. Nevertheless, studies that have evaluated the links between child abuse, dysregulation of the HPA axis, and mental disorders have shown diverse results. Because of the variety of methods employed in the different studies, no formal comparisons have been made. In this systematic review, we have brought together these results. We conducted a systematic review of studies analyzing the correlation between child abuse, mental disorders, and HPA axis activity in patients aged between 6 and 16 years. PubMed, Scopus, Cochrane, and Google Scholar were searched using relevant keywords and inclusion/exclusion criteria (from 2000 to 2020). Fifteen studies from the 351 identified were included. Most patients were children in the child welfare system. Children who had experienced child abuse presented with more severe mental disorders (particularly in the dimensional measure) than children who had not been abused. HPA axis activity was assessed by measuring basal cortisol for some studies and cortisol reactivity for other studies. For children experiencing child abuse, there was a possible association between abuse and a decrease in the reactivity of the HPA axis. In addition, early life stress could be associated with lower matinal cortisol. However, the association between mental disorders and cortisol secretion in maltreated children did not seem obvious. This systematic review demonstrates that mental disorders are more frequent and severe in cases where child abuse has occurred. Moreover, children who experienced child abuse seem to present changes in the reactivity of the HPA axis. Nevertheless, the potential correlation between these changes in the reactivity of the HPA axis and mental disorders in this population needs to be evaluated in further studies.