Psychoneuroendocrinology
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Psychoneuroendocrinology · Sep 2013
ReviewThe three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.
Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. ⋯ Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances.
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Psychoneuroendocrinology · Jan 2013
ReviewGlucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis--2012 Curt Richter Award Winner.
Low birthweight, a marker of an adverse in utero environment, is associated with cardiometabolic disease and brain disorders in adulthood. The adaptive changes made by the fetus in response to the intra-uterine environment result in permanent changes in physiology, structure and metabolism, a phenomenon termed early life programming. One of the key hypotheses to explain programming, namely over exposure of the developing fetus to glucocorticoids, was proposed nearly two decades ago, following the observation that the fetus was protected from high glucocorticoid levels in the mother by the actions of the placental barrier enzyme, 11β-hydroxysteroid dehydrogenase, which converts active glucocorticoids into inactive products. ⋯ In a recent study we showed that alterations in DNA methylation at genes important in regulating cortisol levels, tissue glucocorticoid action, blood pressure and fetal growth, are present in adulthood in association with both early life parameters and cardiometabolic risk factors. These preliminary data add to the limited literature in humans indicating a persisting epigenetic link between early life events and subsequent disease risk. Such findings open novel avenues for further exploration of the contribution of glucocorticoids to later life disease.
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Psychoneuroendocrinology · Aug 2012
ReviewSex differences in physiological reactivity to acute psychosocial stress in adolescence.
Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic-pituitary-adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. ⋯ This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes.
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Testosterone concentrations fluctuate rapidly in response to competitive and aggressive interactions, suggesting that changes in testosterone rather than baseline differences shape ongoing and/or future competitive and aggressive behaviors. Although recent experiments in animal models provide compelling empirical support for this idea, studies in humans have focused largely on how competitive interactions drive changes in testosterone concentrations and not how these changes influence subsequent behavior. ⋯ We also speculate on one putative neural mechanism through which testosterone may bias human aggressive behavior. Finally, we conclude by highlighting important questions that should be addressed in future research.
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Psychoneuroendocrinology · Dec 2009
ReviewNeuroactive steroids: an update of their roles in central and peripheral nervous system.
After five editions, the congress on "Steroids and Nervous System" held in Torino, Italy, represents an important international event for researchers involved in this field aimed to recapitulate mechanisms, physiological and pharmacological effects of neuroactive steroids. The present review introduces manuscripts collected in this supplement issue which are based on new interesting findings such as the influence of sex steroids on cannabinoid-regulated biology, the role of steroids in pain, the importance of co-regulators in steroidal mechanisms and the understanding of new non classical mechanism, the emerging role of vitamin D as a neuroactive steroid and the pathogenetic mechanisms mediated by glucocorticoid receptors. Finally, we have integrated these aspects with an update on some of the several and important observations recently published on this hot topic.