Measurement of cortisol in saliva: a comparison of measurement error within and between international academic-research laboratories.

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Background:

OBJECTIVE: Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross-study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigorously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults (Mean age: 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants’ saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay.

RESULTS: 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established-qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values.

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Individual differences in early adolescents’ latent trait cortisol: Interaction of early adversity and 5-HTTLPR

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Background:

The present study aimed to examine the interaction of 5-HTTLPR and early adversity on trait-like levels of cortisol. A community sample of 117 early adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping, and saliva samples for assessing cortisol 3 times a day (waking, 30min post-waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was modeled using the first 2 samples of each day. Early adversity was assessed with objective contextual stress interviews with adolescents and their mothers. A significant 5-HTTLPR×early adversity interaction indicated that greater early adversity was associated with lower LTC levels, but only among individuals with either L/L or S/L genotype. Findings suggest that serotonergic genetic variation may influence the impact of early adversity on individual differences in HPA-axis regulation. Future research should explore whether this interaction contributes to the development of psychopathology through HPA axis functioning.

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New Collaborative Research at the Naval Health Research Center

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NHRC Biobehavioral Science Laboratory
Our new IISBR Faculty (Kate and Jenna and Beth) and the IISBR staff traveled with Dr. Granger to visit the Naval Health Research Center in Pt Loma, CA. The UCI team spent the day with Dr. Marc Taylor’s research group at the NHRC Biobehavioral Science Laboratory planning collaborative salivary bioscience research to advance our understanding of risk and resilience, and integrative health, in the military.

Long-Term Effects of Prematurity, Cumulative Medical Risk, and Proximal and Distal Social Forces on Individual Differences in Diurnal Cortisol at Young Adulthood.

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Background:

This study examined the effects of prematurity, cumulative medical risk, and proximal and distal social forces on individual differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in young adulthood. A prospective sample of 149 infants born healthy preterm (PT; n = 22), sick PT ( n = 93, medical illness, neurological illness, small for gestational age), and full term ( n = 34) was recruited from a Level III neonatal intensive care unit in southern New England between 1985 and 1989 and followed to age 23 years. Cumulative medical risk was indexed across seven assessment waves (spanning 17 years) using medical and neurological health status at birth, toddlerhood (ages 18 and 30 months), childhood (ages 4 and 8 years), and adolescence (ages 12 and 17 years). Distal risk included socioeconomic status (SES) at birth. Proximal social factors were indexed from assessments of the home environment and measures of child vulnerability and maternal self-esteem, involvement, and control style from birth, 4 years, 8 years, and 12 years. At age 23 years, five saliva samples were collected upon awakening, 45 min after waking, 4 hr after waking, 8 hr after waking, and bedtime (later assayed for cortisol). Results reveal effects of cumulative medical risk on the diurnal pattern of HPA axis activity, with moderating effects of SES and proximal social factors. Findings are discussed in terms of implications for contemporary theories related to developmental sensitivity and susceptibility to context and the developmental origins of health and disease theory.

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New gift from the Prentiss Foundation creates research opportunities for Institute for Interdisciplinary Salivary Bioscience Research

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New gift will help lab expand real-life application of non-invasive salivary testing.

A $150,000 gift from the Elisabeth Severance Prentiss Foundation will enable a new direction for the Institute for Interdisciplinary Salivary Bioscience Research: to translate basic scientific research into clinically useful information and methods.

The gift will fund a project to explore the feasibility of using saliva – rather than blood – to monitor lithium levels in patients taking lithium medications.

“The collaborative science happening at the Institute is impressive and we are excited to support their ground breaking research efforts,” says Pamela Alexander, the president of the Elisabeth Severance Prentiss Foundation.

Lithium is used to treat a variety of severe psychiatric and mental health conditions, such as bipolar disorder and schizophrenia. But lithium levels must be closely monitored since the effective therapeutic range is narrow. When dosage levels are too low, there may be no benefit. But when they are too high, there can be negative and toxic side effects.

Withdrawing blood to monitor lithium levels is a fraught process for many patients. Monitoring lithium levels by taking saliva samples – which is a minimally invasive process – holds great promise to make the monitoring process easier without compromising its precision.

The Prentiss Foundation gift is one example of the Institute’s progress from solely focusing on basic science to more broadly focusing on applying that science to the clinical settings that have real impact on people’s health. That broader focus also means looking beyond the hormone markers Institute scientists have been measuring to find and document other indicators in saliva.

The project will be conducted by an interdisciplinary team with experts in pharmacology (Elizabeth Thomas, Ph.D.), psychology and pediatrics (Douglas Granger, Ph.D.), psychiatry (Ruth Benca, M.D.) and and clinical psychology (Kate Kuhlman, Ph.D.).

Thomas, a neuroscientist from Scripps Research Institute in La Jolla, is a visiting researcher who will lead the project. Thomas earned her Ph.D. in pharmacology from UCI in 1994. Her current research links neuroscience and psychology, and she will bring a valuable perspective to the project.

“I am thrilled that Elizabeth recently joined our team at UCI. She is the type of interdisciplinary, collaborative researcher that the Institute always seeks to partner with,” says Granger, who is also the director of the Institute.

Testing blood and, now, saliva for certain indicators can reveal what’s happening in the brain, according to Thomas. And that’s what her research is looking at: how those bodily indicators can illuminate the brain’s inner workings. Finding, documenting and studying those indicators opens up a new research area in neuroscience, since it’s impossible to take samples of a living person’s brain.

For this project, Thomas will be working with Benca, who is also the chair of the Department of Psychiatry and Human Behavior in the UCI School of Medicine, to recruit patients who are taking lithium medications for a clinical study on the effectiveness of saliva sampling.

“This gift from the Prentiss Foundation will not only allow us to expand the scope of our research, but also could directly improve people’s lives. As a researcher, it is rewarding to know that our science helps others,” says Granger.

The interdisciplinary collaboration also reflects the School of Social Ecology’s broader mission.

“Faculty, researchers and students in the School of Social Ecology are committed to interdisciplinary science that drives solutions to problems. It is within this spirit that we are proud of the Institute’s past research accomplishments and are hopeful for the future discoveries this Prentiss Foundation gift will enable,” says Nancy Guerra, dean of the School of Social Ecology.

Exposure to intimate partner violence in utero and infant internalizing behaviors: Moderation by salivary cortisol-alpha amylase asymmetry.

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Background:

Guided by the main tenets of contemporary models of the developmental origins of health and disease, this study evaluated whether individual differences in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and Sympathetic Nervous System (SNS) moderate the effect of prenatal exposure to trauma on internalizing and externalizing behaviors during infancy. Participants were a community sample of 182 mothers (M age=25years, 43% Caucasian, 33% Black/African American, 24% Biracial/Other) and their infants (59% girls; M age=11.8months). Each mother completed questionnaires that assessed IPV experienced during pregnancy and also reported on her infant’s behavior problems. Infant saliva samples (later assayed for cortisol and sAA) were collected before and after a frustrating task (i.e., arm restraint). Results revealed that the association between in utero IPV and infant internalizing behaviors was most pronounced for infants with asymmetrical HPA-SNS (i.e., high-cortisol and low-sAA) reactivity to frustration, and least pronounced for infants with symmetrical HPA-SNS (i.e., low-cortisol and low-sAA or high-cortisol and high-sAA) reactivity to frustration. Higher levels of externalizing behavior, in contrast, were associated with higher levels of prenatal IPV but unrelated to either cortisol or sAA reactivity to stress. Findings replicate documented associations between maternal IPV exposure during pregnancy and offspring risk. Moreover, findings advance our understanding of individual differences in the developmental origins of health and disease and provide additional evidence that assessing multiple stress biomarkers contributes to a more comprehensive understanding of individual vulnerability to adversity.

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Assistant/Associate Professor, Salivary Bioscience and Clinical Psychology

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Description

The Department of Psychology and Social Behavior at the University of California, Irvine invites applications for a full-time, tenure‐track or tenured faculty position in Salivary Bioscience and Clinical Psychology. The position will be at the rank of Assistant Professor or Associate Professor. Candidates must have a doctoral degree in psychology, with a specialization in clinical psychology and eligibility for licensure. Successful applicants will contribute to a broader, interdisciplinary initiative in salivary bioscience at UCI, and will collaborate with other faculty members and research scientists affiliated with a newly established UCI Institute for Interdisciplinary Salivary Bioscience Research (http://iisbr.uci.edu/). Applications are encouraged from individuals whose scholarship emphasizes the use of salivary biomarkers to address theory‐driven questions in the field of clinical psychology. We also welcome applications from individuals who can contribute to salivary biomarker discovery and measurement. Applicants should have an outstanding record of research, evidence of the ability to attract extramural funding, and evidence of excellent teaching and mentoring. Priority will be given to applications received by September 15, 2017; however, applications will be accepted until the position is filled.

Application materials must be submitted electronically (please refer to the employment link at the following website for instructions: https://recruit.ap.uci.edu/apply/JPF04182. Candidates must submit a letter of interest, a curriculum vitae, statements of research and teaching interests, representative publications, and arrange to have three letters of recommendation uploaded electronically. A separate statement that addresses past and/or potential contributions to diversity, equity and inclusion must also be included in the application materials. Please direct questions about this position to Diane Enriquez at d.enriquez@uci.edu.

The University of California, Irvine is an Equal Opportunity/Affirmative Action Employer advancing inclusive excellence. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, protected veteran status, or other protected categories covered by the UC nondiscrimination policy. A recipient of an NSF ADVANCE award for gender equity, UCI is responsive to the needs of dual career couples, supports work‐life balance through an array of family‐friendly policies, and is dedicated to broadening participation in higher education.

Salivary biomarkers for Huntington’s disease

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Background:

OBJECTIVE: The objective of the current study was to assess the potential for saliva to serve as a biospecimen for accessible biomarkers for Huntington’s disease (HD).

BACKGROUND: Peripheral biomarkers are greatly needed in the field of neurodegenerative disorders to anticipate onset of disease symptoms, monitor disease progression, and track potential therapeutic effects. HD is a fatal, inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene encoding the protein, huntingtin (Htt). Pathogenesis is associated with expression of the mutant Htt (mHtt) protein in the CNS; however, HD is also associated with abnormalities in peripheral tissues. The Htt protein is the most significant molecular target for disease modifying therapies, and several therapeutic approaches directed at its production, processing, and/or turnover are under development for impending clinical trials. Measuring Htt and other disease proteins in peripheral cells represents an essential step in biomarker discovery for HD.

DESIGN/METHODS: In the current study, we measured Htt protein in saliva from manifest HD patients, gene-positive premanifest HD patients, and age- and sex-matched normal individuals (total n=178) using Western blots and ELISA methods. Additional salivary analytes, including alpha amylase, cortisol, C-reactive protein (CRP), and uric acid, were also measured using standardized ELISAs.

RESULTS: Salivary total Htt levels were significantly increased (p=0.0012) in saliva from HD individuals (mean=0.775 ng/ml) compared to normal controls (mean=0.359 ng/ml). Salivary total Htt did not vary over time of day or over different days, nor were there age or gender effects. Additionally, salivary mHtt levels were higher in gene positive premanifest HD subjects compared to normal controls (p<0.05). CRP, a widely used biomarker of systemic inflammation, was found to be significantly (p=0.025) elevated in premanifest HD subjects (9,548 pg/ml) compared to normal controls (3,399 pg/ml) and may be an early marker for disease onset. Levels of other salivary proteins, alpha amylase and uric acid, were not significantly different between HD patients, premanifest subjects, or normal controls.

CONCLUSIONS: Measurement of salivary Htt and other disease proteins offers significant promise as relevant, non-invasive biomarkers of disease onset and progression in HD.

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The “yin and yang” of the adrenal and gonadal systems in elite military men.

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Background:

We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the “positive coupling” hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the “yin and yang” of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

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Social Ecology hires two new faculty members to collaborate with Institute for Interdisciplinary Salivary Bioscience Research

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Jenna Riis and Kate Kuhlman

May 2017

The School of Social Ecology has hired two new assistant professors, Jenna Riis and Kate Kuhlman, to work in the Department of Psychology and Social Behavior, effective July 1, 2017. Both plan to develop research collaborations with the Institute for Interdisciplinary Salivary Bioscience Research, which uses saliva to better understand important issues such as stress, heart disease risk, animal wellness, infectious diseases and much more.

Riis earned her PhD at Johns Hopkins Bloomberg School of Public Health in Baltimore, MD. For the last couple years, she has worked as an early childhood mental health specialist at the New York City Department of Health and Mental Hygiene.

Her research uses salivary biomeasures to advance child health research, and examine the effects of early-life adversity. She also seeks to use salivary biomarkers to broaden the range of lines of study for child health researchers, and measure the effectiveness of intervention programs on child health. Her research may help identify, prevent and treat the effects of childhood adversity.

Kuhlman earned her PhD in clinical psychology at the University of Michigan, and has worked as a postdoctoral fellow at University of California, Los Angeles for the past few years.

Her research seeks to mitigate the lifelong health disparities that are associated with childhood trauma, maltreatment and unpredictable family environments. She measures responses to stress at the behavioral, cognitive, molecular and even intracellular levels, and examines how those responses affect depression and other disorders. By identifying predictors of resilience among at-risk youth, she also seeks to inform intervention programs.

 

 

UCI School of Social Ecology
Social Ecology I
Irvine, CA 92697-7050
www.uci.edu
www.socialecology.uci.edu