Transcript The Integration of Biomarkers to Advance Caregiver Science across

Integration of Biomarkers to
Advance Family Nursing
Research Across the
Lifespan
Elizabeth Corwin, PhD, RN, FAAN,
Emory University
School of Nursing
Funding Acknowledgement
•
Psychoneuroimmune Contributions to Postpartum Depression
(R01NR011278, National Institute of Nursing Research)
•
Biobehavioral Determinants of the Microbiome and Preterm Birth in
Black Women (R01NR014800, National Institute of Nursing Research)
I have no conflicts of interest to report
Family Caregiving
•
•
•
>30 million individuals in U.S. provide care annually for
chronically ill, disabled or aged family member
Care is often:
• longitudinal
• with worsening trajectories for loved ones
• physically demanding
• isolating, lonely, & sad
• frightening (financially & physically)
Example:
• Caregivers of family members with dementia provide an
average of 16.6 hours/week–for years.
(National Alliance for Caregiving, in collaboration with AARP, 2009)
(Schultz and Martire, 2004)
Health Outcomes of Caregivers of
Spouses with Alzheimer’s Disease
Multiple adverse outcomes compared to non-caregivers of
same age
• 63% higher mortality rate
• Increased risk of infectious disease
• Increased risk of chronic illness
• Cardiovascular disease (hypertension, MI)
• Diabetes
• Depression
• This limits their ability to provide care
•
•
(Kiecolt-Glaser, et al., 2008; Gouin, et al., 2008)
Family Caregiving
• Caregiving crosses generations
• As does its impact – on caregiver and recipient
Adverse Health Outcomes of Family
Caregivers Across the Lifespan
•
•
•
•
•
Spouses of patients with cancer (Li &Like, 2013; Haley, et al., 2003; Jassem, Haley,
et al., 2015)
Parents of autistic children (Lovell et al., 2012; 2015)
Parents of children with TBI (Wharewere-Mika, et al., 2015)
Mothers of children and adolescents with pediatric cancer (Miller et al., 2008;
Rohleder, et al, 2009; Palma et al., 2015)
Mothers of children who die(Jiong et al., 2003; Espinosa,Evans, 2013)
Common Denominator: Chronic Stress
Normally… with acute stress
Pro-inflammatory cytokines
Cortisol
* Limits exaggerated inflammation
* Limits exaggerated production of cortisol
However…
With exposure to chronic stress
Cells may develop glucocorticoid resistance (GR)
• Cortisol cannot limit cytokine production
•
• Leads to dysregulation of inflammatory response
Cortisol partially escapes negative feedback
• Leads to increased cortisol
BOTH OF WHICH ADVERSELY IMPACT MOOD and HEALTH
Pro-inflammatory cytokines
cortisol
How do they advance Family Nursing Research?
WHY INCLUDE BIOMARKERS?
Biomarkers
•
What they are:
• Measurable indicators of health, a state, or a disease
• Human chorionic gonadotropin (hCG)
• Prostate specific antigen (PSA)
• Cholesterol
• HbgA1c
• Atrial or brain natiuretic peptide (ANP/BNP)
• C-reactive protein (CRP)
• Diurnal salivary cortisol
• Pro- and anti-inflammatory cytokines
• Reactive oxygen species
• Brain-derived neurotrophic factor (BDNF)
• Telomeres & telomerase
What about the Care Recipient?
• What are the health outcomes?
Telomere Length: A Marker of Cellular
Aging – An Indicator of Chronic Stress
 Reduced telomere length in mothers with
chronically ill children
(Epel, et al., Proceedings of the Natl Acad Sci, 2004)
 Reduced telomere length in long-term caregivers of
Alzheimer’s patients (Gamjanovic, et al., J of Immunology, 2007)
 Reduced telomere length in children of depressed
mothers (Gotlib, et al., Molecular Psychiatry, 2015)
 Shorter telomere length in newborns related to
maternal prenatal depression (Entringer, et al., Am J Obstet Gynecol,
2013)
What the Inclusion of Biomarkers
Adds To Family Nursing Research
•
•
The potential to uncover the underlying biological mechanism
responsible for a particular symptom or an adverse health outcome
The potential for precision nursing interventions
•
•
If you know the mechanism, you can target it
If you target it, you can measure your success
• Over time
• In real time
An Exemplar:
Spontaneous Preterm Birth
• Most common type of preterm birth
• Associated with significant adverse outcomes for
families
• Risk factors include
• Previous preterm birth
• Infection/Inflammation
• Chronic Stress & elevated HPA axis hormones
• Mechanisms remain unclear
• Interventions to predict or prevent PTB of limited
success
Step 1
Uncover the Mechanism
Minority and low-income pregnant women
experience > risk of PTB than Caucasian
and/or higher income women
Minority and low-income pregnant
women report increased chronic
stress compared to Caucasian and
higher income women (Geronimous, 2008)
A Biological Fingerprint of Disadvantage
• In our longitudinal study of 201 healthy, pregnant women,
followed from the 3rd trimester through 6-months
postpartum
• We identified PNI dysregulation and loss of the
bidirectional cytokine-cortisol feedback in pregnant
low income and minority women compared to
higher income Caucasian women.
(Corwin, et al., Psychoneuroendocrinology, 2013)
• PNI dysregulation and loss of feedback continued through
6-months postpartum
Average daily cortisol concentration (mean+SE) (AUC)
in Caucasian higher income women compared to minority
and low income pregnant and postpartum women
Pro-Inflammatory cytokine levels in
Caucasian/higher income women vs minority/low
income pregnant and postpartum women
Cytokine-glucocorticoid feedback in Caucasian/higher
income women vs minority/low income pregnant women
All slopes significant for Caucasian/higher income pregnant women (blue) but not
lower income/minority pregnant women(red) (*p<0.05, **p<.001, ***p<.0001)
Month 3 postpartum cytokine-glucorticoid feedback in
Caucasian/higher income women (blue) vs minority/low
income (green) postpartum women
All slopes significant for Caucasian/higher income pregnant women
(blue) but not lower income/minority pregnant women (green)
OUR CURRENT STUDY: Focusing on the Population Most at Risk
AFRICAN-AMERICAN FAMILY CARETAKERS
Effects of Chronic Stress on the
Microbiome and PTB in Black Women
(R01NR014800)
•
Gut microbiome mirrors our stress
•
Elevated cortisol “leaky gut”
•
•
Oral microbiome
•
•
increases inflammation
A source blood borne infection or systemic inflammation
Vaginal microbiome
A route to PTB
Step 2: Precision - Tailor the Intervention
•
•
•
Go back to the mechanism
Chronic stress Inflammation and cortisol
Design an intervention to  Chronic Stress
or
Design an intervention to change a women’s response to
chronic stress
Mindfulness
Yoga
Exercise
Singing
Spirituality
Step 3: Test the Intervention
• Go back to the mechanism
- Chronic stress inflammation and increased cortisol
• Target the patient
- Does this person show the phenotype predictive of PNI
dysregulation?
•
If so…
• Test the intervention
- Did it work?
• Did it return normal cytokine-glucocorticoid feedback?
• Did it reduce inflammation? Cortisol?
• Did it return the microbiome to more protective state?
Family Caregiving
Integrating biomarkers can help predict and guide
precision family nursing research & care
across
generations
Thank You
QUESTIONS?