The influence of light wavelength on HPA axis function in non-human animals: A meta-analysis.

Blood mRNA expression levels of glucocorticoid receptors and FKBP5 are associated with depressive disorder and altered HPA axis

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India

Cortisol response patterns in depressed women and their healthy daughters at risk: Comparison with healthy women and their daughters

Venlafaxine drug interaction in the diagnosis of pheochromocytoma

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016.

The roles of comorbidity and trauma exposure and its timing in shaping HPA axis patterns in depression

Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

The effects of pre-hatch elevated corticosterone and post-hatch restrictive food availability on the HPA axis development of mallard ducks (Anas platyrhynchos)

The association between the hypothalamic pituitary adrenal axis and tryptophan metabolism in persons with recurrent major depressive disorder and healthy controls

The circadian timing system and integrated stress response (ISR) systems are fundamental regulatory mechanisms that maintain body homeostasis. The central circadian pacemaker in the suprachiasmatic nucleus (SCN) governs daily rhythms through interactions with peripheral oscillators via the hypothalamus-pituitary-adrenal (HPA) axis. On the other hand, ISR signaling is pivotal for preserving cellular homeostasis in response to physiological changes. Notably, disrupted circadian rhythms are observed in cases of impaired ISR signaling. In this work, we examine the potential interplay between the central circadian system and the ISR, mainly through the SCN and HPA axis. We introduce a semimechanistic mathematical model to delineate SCN's capacity for indirectly perceiving physiological stress through glucocorticoid-mediated feedback from the HPA axis and orchestrating a cellular response via the ISR mechanism. Key components of our investigation include evaluating general control nonderepressible 2 (GCN2) expression in the SCN, the effect of physiological stress stimuli on the HPA axis, and the interconnected feedback between the HPA and SCN. Simulation revealed a critical role for GCN2 in linking ISR with circadian rhythms. Experimental findings have demonstrated that a Gcn2 deletion in mice leads to rapid re-entrainment of the circadian clock following jetlag as well as to an elongation of the circadian period. These phenomena are well replicated by our model, which suggests that both the swift re-entrainment and prolonged period can be ascribed to a reduced robustness in neuronal oscillators. Our model also offers insights into phase shifts induced by acute physiological stress and the alignment/misalignment of physiological stress with external light-dark cues. Such understanding aids in strategizing responses to stressful events, such as nutritional status changes and jetlag.NEW & NOTEWORTHY This study is the first theoretical work to investigate the complex interaction between integrated stress response (ISR) sensing and central circadian rhythm regulation, encompassing the suprachiasmatic nucleus (SCN) and hypothalamus-pituitary-adrenal (HPA) axis. The findings carry implications for the development of dietary or pharmacological interventions aimed at facilitating recovery from stressful events, such as jetlag. Moreover, they provide promising prospects for potential therapeutic interventions that target circadian rhythm disruption and various stress-related disorders.

Hypothalamic pituitary adrenal (HPA) axis functioning, as measured by the dexamethasone suppression test (DST), has been extensively investigated in major depressive disorder (MDD). Evaluating DST response in MDD patients while simultaneously considering clinically relevant personality disorders may further clarify the contribution of both personality pathology and HPA axis function to depressive symptoms. The present study measured personality pathology by administering the revised version of the Millon Clinical Multiaxial Inventory (MCMI-II) in a sample of 25 patients diagnosed with MDD. Analyses revealed that suppressors (n = 19) scored significantly higher than non-suppressors (n = 6) on six of the 13 MCMI-II personality disorder scales: Avoidant, Schizoid, Self-Defeating, Passive-Aggressive, Schizotypal and Borderline. Increased personality pathology was associated with normal suppression of cortisol following the DST. This suggests that suppression of the DST may be associated with depressive states linked with personality pathology while the more biologically based depression is associated with abnormal HPA pathophysiology. Copyright 2001 John Wiley & Sons, Ltd.

Neural regulation of circadian rhythms.

Aims: The hypothalamic pituitary adrenal (HPA) axis is the key neuroendocrine mediator of the stress response and controls many aspects of physiology and behavior. We previously showed that experimentally disrupting normal HPA function in mice led to altered neural and behavioral responses to acute stress. When exposed to prolonged or repeated stress, organisms undergo adaptation in many processes of metabolism, endocrine function, and behavior. Further, many of these processes are thought to be driven by HPA secreted hormones. In this study, we aimed to test this hypothesis by disrupting normal HPA axis function and measuring metabolic, endocrine, and neural outcomes following repeated stress exposure. Methods: HPA axis function in male C57BL/6 mice was disrupted via noninvasive, oral corticosterone administration, which we have shown blunts hormonal and behavioral stress responses. Mice were then exposed to repeated immobilization stress (2h/d for 14d), during which time body weight was measured to assess metabolic adaptation to stress. Mice were euthanized and adipose tissue, adrenal glands, blood, and brain were collected for analysis. We evaluated the effects of HPA disruption on mass of white adipose tissue and adrenal glands, and determined plasma corticosterone concentrations as a measure of endocrine adaptation to stress. Using RTqPCR we investigated the effects of HPA disruption on the expression of genes related to synaptic excitability in the medial prefrontal cortex (mPFC), a brain region known to regulate behavioral and emotional responses to stress. Results: Repeated stress led to body weight loss in all mice, however body weight loss was exaggerated by HPA disruption, suggesting increased sensitivity to stress. Additionally, this decrease in body weight could not be accounted for by decreased white adipose mass alone, suggesting effects on other tissues caused by HPA disruption. Repeated stress increased adrenal weight similarly in all mice, but only elevated levels of plasma corticosterone in Control mice, demonstrating altered endocrine adaptation to stress after HPA disruption. Finally, we observed increased gene expression of the astrocytic glutamate exchanger xCT in the mPFC following repeated stress only in HPA disrupted mice, suggesting that HPA disruption affects processes of neural adaptation. Conclusions: HPA axis disruption increased sensitivity to metabolic outcomes of repeated stress exposure and altered endocrine stress adaptation. Additionally, effects on mPFC gene expression suggest altered neural adaptation to stress. These results support the hypothesis that an intact HPA axis is crucial in mediating adaptive responses to stress, and that dysfunction of this system may be linked to negative health outcomes of stress exposure. Sources of Research Support: NSF 1553067 and NIA R21AG050054 to INK.

Salivary Cortisol: A Tool for Biobehavioral Research in Children

The chronic variable stress (CVS) paradigm is frequently used to model the changes in hypothalamic pituitary adrenal (HPA) axis function characteristic of many stress-related diseases. However, male C57BL/6 mice are typically resistant to CVS’s effects, making it difficult to determine how chronic stress exposure may alter acute HPA function and regulation in these mice. As social support in rodents can profoundly influence physiological and behavioral processes, including the HPA axis, we sought to characterize the effects of CVS exposure on basal and acute stress-induced HPA axis function in pair- and single-housed adult male mice. Despite all subjects exhibiting decreased body weight gain after six weeks of CVS, the corticosterone response to a novel, acute restraint stressor was enhanced by CVS exclusively in single-housed males. CVS also significantly increased arginine vasopressin (AVP) mRNA in the hypothalamic paraventricular nucleus (PVN) in single-housed males only. Moreover, in single-, but not pair-housed mice, CVS attenuated decreases in circulating OT found following acute restraint. Only the effect of CVS to elevate PVN corticotropin releasing hormone (CRH) mRNA levels after an acute stressor was restricted to pair-housed mice. Collectively, our findings suggest that social isolation reveals effects of CVS on the HPA axis in male C57BL/6 mice.