Glucocorticoid sensitivity and well-being in aging: bi-directional relationships (Project funded through the National Institute on Aging)
Levels of the hormone cortisol are tightly regulated via a process known as negative feedback: cortisol “turns off” its own production, thus quickly reining in cortisol levels after an increase. Individuals vary in their degree of negative feedback, depending on their glucocorticoid sensitivity: in other words, how well their brains can detect and respond to cortisol. Interestingly, major depression is associated with lower than average glucocorticoid sensitivity and HPA negative feedback. There is also evidence that negative feedback is not a static trait but can change within an individual over time, e.g. when the depression resolves. It is not yet known, though, whether alterations in negative feedback occur first, and lead to development of mood or other health problems, and/or whether mood or health status cause changes in the degree of negative feedback. It is also completely unknown how negative feedback is associated with changes in mood, life stress, health and well-being beyond psychological disease states such as depression. Longitudinal research is needed following individuals over years to understand how this physiological system both affects, and is affected by, mood, health and well-being.
This project addresses these questions by adding measurement of HPA axis negative feedback to the rich longitudinal data set on mood, stress, and health in the Notre Dame Health & Well-Being (NDHWB) study. A bi-directional model is hypothesized, in that a person’s degree of negative feedback both impacts and is impacted by their health and well-being. The project has two goals (Aims) related to this bi-directional model. Aim 1 is to understand which individual difference variables and contextual factors in the preceding 5 years of NDHWB data precede or predict differences in negative feedback. Aim 2 is to investigate which present and future health and well-being measures are associated with or predicted by negative feedback. To test these Aims, participants drawn from the NDHWB, ranging in age from 18-90, complete two study sessions to assess HPA axis negative feedback. This is measured by degree of suppression of an upstream hormone, ACTH, caused by an injection of a low dose of cortisol (compared to a control day with no cortisol injection.) Negative feedback data will be combined with the NDHWB study’s multiple years of data on individual differences, life stress, daily stressors, mood, and health outcomes. This will provide an unprecedented opportunity to discover time-course relationships between stress, mood, and dysregulation in the HPA axis, and will help us understand the development of well-being and resilience against illness across the lifespan.
Effects of oxytocin on cognition and emotion
The hormone oxytocin is considered by some to be an empathy-inducing panacea, and is already being tested as an adjunct treatment for disorders such as autism and schizophrenia. Basic research is lacking, though, on how oxytocin impacts human cognitive functioning. Some researchers believe that oxytocin selectively enhances social information processing. However, fMRI and non-human animal research show broad effects of oxytocin on memory- and emotion-related regions of the brain, including amygdala, hippocampus and prefrontal cortex. With this project, which includes Allison Gaffey's Master's Thesis work, we hope to understand how oxytocin affects not just social memory, but other aspects of human memory and cognition. We are also investigating for the first time oxytocin's effects on other hormonal systems and on peripheral physiological responses to emotional stimuli. Our collaborations with George Anderson (Yale), Stephanie Brown (SUNY-Stonybrook), and Michael Poulin (U. at Buffalo) allow us to study effects of oxytocin nasal spray on peripheral oxytocin levels, and genetic influences on the effects of oxytocin, among other questions.
Neurosteroids: roles in stress, emotion, and psychopathology
We are interested in a set of hormones made from progesterone and called neurosteroids. From past research in animals, we know that neurosteroids have important inhibitory effects on neurons, and anti-stress effects in the brain. Also, levels of certain neurosteroids are lower in people with depression or PTSD compared to healthy people. However, very little is currently known about how these hormones respond to stress and affect cognition and emotion in humans. Along with Professors William Boggess and Michelle Joyce in the Department of Chemistry and Biochemistry, we are developing a method to extract and quantify neurosteroids in blood samples using mass spectrometry. This will allow us to examine how neurosteroids relate to emotional memory, and other aspects of emotion and cognition that are altered in depression and PTSD.
Closeness and helping
What roles do hormones play in empathy, trust, and helping behavior? Several studies in the lab address these questions, using tools including oxytocin nasal spray, tests of empathy, and a closeness-generating task (Aron et al., 1997).
Effects of early trauma on stress hormones and memory
Michael Meaney and colleagues have shown that early life experiences (i.e. maternal care differences) in rodents cause lifelong changes in glucocorticoid receptor gene expression, and therefore how glucocorticoids influence long-term potentiation and memory function. Along with Professors Jessica Payne and Kristin Valentino and Ph.D. students Tony Cunningham, Steve Mattingly and Amy Nuttall, we are examining these issues in humans. As a starting point, we collaborated to design a study examining memory as a function of cortisol levels in women with or without a child abuse history.
Oxytocin and motivation to eat
Oxytocin is not only a hormone of affiliation and social cognition, but plays multiple physiological roles, including in satiety (the termination of hunger). With neuroscientists Professors Pawel Olszewski (U. of Waikato, New Zealand) and Allen Levine (U. of MN), and cognitive psychologists Professors James Brockmole and Chris Davoli, we are extending findings from rodent models to humans to examine whether oxytocin affects motivational responses to food stimuli, as captured by attention, and food sharing.
Our lab collaborates with Professor Jessica Payne, Tony Cunningham, and others in the Sleep, Stress and Memory Lab on a number of projects, including studying how sleep moderates the effects of stress on emotional memory.
Our lab also has a collaboration with Professor Cindy Bergeman to study the relationship of daily cortisol profiles to stressors and well-being in the Notre Dame Study of Health and Well-Being.
Completed Projects (data analysis ongoing)
Laboratory stressors, hormones, and affiliation
Allison Gaffey spearheaded a series of studies designed to: (1) examine progesterone, cortisol, and subjective emotional responses to three different laboratory stressors: the Trier Social Stress Test (Kirschbaum et al. 1993), the Social-Evaluative Cold Pressor Test (Schwabe et al. 2008), and the Cyberball rejection task (Williams et al. 2000), and (2) determine roles of hormonal responses in the motivation to respond to stress by reaching out to a friend. Allison and Dr. Wirth have authored a manuscript based on these findings which is now published in the journal F1000.
Intravenous cortisol: effects on cognition and physiology (Professor Wirth's post-doctoral research)
This study, conducted with Professor Heather Abercrombie (U. WI), was designed to concurrently examine cortisol's effects on stress physiology (HPA axis negative feedback) and its effects on cognition (emotional memory), using intravenous administration of cortisol to human subjects. Publications arising from this work are available here (Wirth, Scherer, Hoks, & Abercrombie, 2011) and here (Abercrombie, Wirth, & Hoks, 2011).