Posts tagged HPA axis
Articles and news from the latest research reports.
Maturing brain flips function of amygdala in regulating stress hormones
In contrast to evidence that the amygdala stimulates stress responses in adults, researchers at Yerkes National Primate Research Center, Emory University have found that the amygdala has an inhibitory effect on stress hormones during the early development of nonhuman primates.
The results are published this week in Journal of Neuroscience.
The amygdala is a region of the brain known to be important for responses to threatening situations and learning about threats. Alterations in the amygdala have been reported in psychiatric disorders such as depression, anxiety disorders like PTSD, schizophrenia and autism spectrum disorder. However, much of what is known about the amygdala comes from research on adults.
"Our findings fit into an emerging theme in neuroscience research: that during childhood, there is a switch in amygdala function and connectivity with other brain regions, particularly the prefrontal cortex,” says Mar Sanchez, PhD, neuroscience researcher at Yerkes and associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. The first author of the paper is postdoctoral fellow Jessica Raper, PhD.
The findings are part of a larger longitudinal study at Yerkes National Primate Research Center, examining how amygdala damage within the first month of life affects the development of social and emotional behaviors and neuroendocrine systems in rhesus monkeys from infancy through adulthood. The laboratories of Sanchez and Yerkes researchers Jocelyne Bachevalier, PhD and Kim Wallen, PhD are collaborating on this project.
Previous investigations at Yerkes found that as infants, monkeys with amygdala damage showed higher levels of the stress hormone cortisol. This surprising result contrasted with previous research on adults, which showed that amygdala damage results in lower levels of cortisol.
The team hypothesized that damage to the amygdala generated changes in the HPA axis: a network of endocrine interactions between the hypothalamus within the brain, the pituitary and the adrenal glands, critical for reactions to stress.
"We wanted to examine whether the alterations in stress hormones seen during infancy persisted, and what brain changes were responsible for them," Sanchez says. "In studies of adults, the amygdala and its connections are fully formed at the time of the manipulation, but here neither the amygdala or its connections were fully matured when the damage occurred."
In the current paper, the authors demonstrated that in contrast with adult animals with amygdala damage, juvenile monkeys with early amygdala damage had increased levels of cortisol in the blood, compared to controls. In their cerebrospinal fluid, they also had elevated levels of corticotropin releasing factor (CRF), the neuropeptide that initiates the stress response in the brain. Elevated CRF and cortisol are linked to anxiety and emotional dysregulation in patients with mood disorders.
Despite the increased levels of stress hormones, monkeys with early amygdala damage exhibit a blunted emotional reactivity to threats, including decreased fear and aggression, and reduced anxiety in response to stress. Still, monkeys with neonatal amygdala damage remain competent in interacting with others in their large social groups. These findings are consistent with reports of human patients with damage to the amygdala, Raper says.
"We speculate that the rich social environment provided to the monkeys promotes compensatory mechanisms in cortical regions implicated in the regulation of social behavior," she says. "But neonatal amygdala damage seems more detrimental for the development of stress neuroendocrine circuits in other areas of the brain."
The investigators plan to follow the animals into adulthood to investigate the long-term effects of early amygdala damage on stress hormones, behavior and physiological systems possibly affected by chronically high cortisol levels, such as immune, growth and reproductive functions.
(Source: news.emory.edu)
Stress is contagious. Observing another person in a stressful situation can be enough to make our own bodies release the stress hormone cortisol. This is the conclusion reached by scientists involved in a large-scale cooperation project between the departments of Tania Singer at the Max Planck Institute for Cognitive and Brain Sciences in Leipzig and Clemens Kirschbaum at the Technische Universität Dresden. Empathic stress arose primarily when the observer and stressed individual were partners in a couple relationship and the stressful situation could be directly observed through a one-way mirror. However, even the observation of stressed strangers via video transmission was enough to put some people on red alert. In our stress-ridden society, empathic stress is a phenomenon that should not be ignored by the health care system.
Stress is a major health threat in today’s society. It causes a range of psychological problems like burnout, depression and anxiety. Even those who lead relatively relaxed lives constantly come into contact with stressed individuals. Whether at work or on television: someone is always experiencing stress, and this stress can affect the general environment in a physiologically quantifiable way through increased concentrations of the stress hormone cortisol.
“The fact that we could actually measure this empathic stress in the form of a significant hormone release was astonishing,” says Veronika Engert, one of the study’s first authors. This is particularly true considering that many studies experience difficulties to induce firsthand stress to begin with. The authors found that empathic stress reactions could be independent of (“vicarious stress”) or proportional to (“stress resonance”) the stress reactions of the actively stressed individuals. “There must be a transmission mechanism via which the target’s state can elicit a similar state in the observer down to the level of a hormonal stress response.“
During the stress test, the test subjects had to struggle with difficult mental arithmetic tasks and interviews, while two supposed behavioural analysts assessed their performance. Only five percent of the directly stressed test subjects managed to remain calm; the others displayed a physiologically significant increase in their cortisol levels.
In total, 26 percent of observers who were not directly exposed to any stress whatsoever also showed a significant increase in cortisol. The effect was particularly strong when observer and stressed individual were partners in a couple relationship (40 percent). However, even when watching a complete stranger, the stress was transmitted to ten percent of the observers. Accordingly, emotional closeness is a facilitator but not a necessary condition for the occurrence of empathic stress.
When the observers watched the events directly through a one-way mirror, 30 percent of them experienced a stress response. However, even presenting the stress test only virtually via video transmission was sufficient to significantly increase the cortisol levels of 24 percent of the observers. “This means that even television programmes depicting the suffering of other people can transmit that stress to viewers,” says Engert. “Stress has enormous contagion potential.”
Stress becomes a problem primarily when it is chronic. “A hormonal stress response has an evolutionary purpose, of course. When you are exposed to danger, you want your body to respond with an increase in cortisol,” explains Engert. “However, permanently elevated cortisol levels are not good. They have a negative impact on the immune system and neurotoxic properties in the long term.” Thus, individuals working as caregivers or the family members of chronically stressed individualshave an increased risk to suffer from the potentially harmful consequences of empathic stress. Anyone who is confronted with the suffering and stress of another person, particularly when sustained, has a higher risk of being affected by it themselves.
The results of the study also debunked a common prejudice: men and women actually experience empathic stress reactions with equal frequency. “In surveys however, women tend to assess themselves as being more empathic compared to men’s self-assessments. This self-perception does not seem to hold if probed by implicit measures”
Future studies are intended to reveal exactly how the stress is transmitted and what can be done to reduce its potentially negative influence on society.
Neurobiologists find chronic stress in early life causes anxiety, aggression in adulthood
In recent years, behavioral neuroscientists have debated the meaning and significance of a plethora of independently conducted experiments seeking to establish the impact of chronic, early-life stress upon behavior – both at the time that stress is experienced, and upon the same individuals later in life, during adulthood.
These experiments, typically conducted in rodents, have on the one hand clearly indicated a link between certain kinds of early stress and dysfunction in the neuroendocrine system, particularly in the so-called HPA axis (hypothalamic-pituitary-adrenal), which regulates the endocrine glands and stress hormones including corticotropin and glucocorticoid.
Yet the evidence is by no means unequivocal. Stress studies in rodents have also clearly identified a native capacity, stronger in some individuals than others, and seemingly weak or absent in still others, to bounce back from chronic early-life stress. Some rodents subjected to early-life stress have no apparent behavioral consequences in adulthood – they are disposed neither to anxiety nor depression, the classic pathologies understood to be induced by stress in certain individuals.
This week, a research team led by Associate Professor Grigori Enikolopov of Cold Spring Harbor Laboratory (CSHL) reports online in the journal Plos One the results of experiments designed to assess the impacts of social stress upon adolescent mice, both at the time they are experienced and during adulthood. Involving many different kinds of stress tests and means of measuring their impacts, the research indicates that a “hostile environment in adolescence disturbs psychoemotional state and social behaviors of animals in adult life,” the team says.
The tests began with 1-month-old male mice – the equivalent, in human terms of adolescents – each placed for 2 weeks in a cage shared with an aggressive adult male. The animals were separated by a transparent perforated partition, but the young males were exposed daily to short attacks by the adult males. This kind of chronic activity produces what neurobiologists call social-defeat stress in the young mice. These mice were then studied in a range of behavioral tests.
“The tests assessed levels of anxiety, depression, and capacity to socialize and communicate with an unfamiliar partner,” explains Enikolopov. They showed that in young mice, chronic social defeat induced high levels of anxiety and helplessness, and less social interaction, including diminished ability to communicate with other young animals. Stressed mice also had less new nerve-cell growth (neurogenesis) in a portion of the hippocampus known to be affected in depression: the subgranular zone of the dentate gyrus.
Another group of young mice was also exposed to social stress, but was then placed for several weeks in an unstressful environment. Following this “rest” period, these mice, now old enough to be considered adults, were tested in the same manner as the other cohort.
In this second, now-adult group, most of the behaviors impacted by social defeat returned to normal, as did neurogenesis, which retuned to a level seen in healthy controls. “This shows that young mice, exposed to adult aggressors, were largely resilient biologically and behaviorally,” says Enikolopov.
However, in these resilient mice, the team measured two latent impacts on behavior. As adults they were abnormally anxious, and were observed to be more aggressive in their social interactions. “The exposure to a hostile environment during their adolescence had profound consequences in terms of emotional state and the ability to interact with peers,” Enikolopov observes.