Hair cortisol and depressive symptoms in youth: An investigation of curvilinear relationships

doi:10.1016/j.psyneuen.2019.104376

Psychoneuroendocrinology

Volume 109, November 2019, 104376

https://doi.org/10.1016/j.psyneuen.2019.104376 Get rights and content

Highlights

•
Adolescent hair cortisol levels were not significantly associated with depressive symptoms in the linear model.
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Adolescent hair cortisol levels at the low and high end of the sample distribution were associated with increased depressive symptoms.
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Significant sex differences in the curvilinear relationship between hair cortisol levels and depressive symptoms were not found.

Abstract

Background

As the prevalence of depression is increasing among youth in the U.S., research on the utility of biomarkers in predicting depressive symptomatology is burgeoning. Hair cortisol may be a useful biomarker as it is a retrospective and longer-term measure of the mean cortisol level. However, studies have yet to examine the relationships between hair cortisol and depressive symptoms in samples of youth, and findings with adult samples are mixed. This study examined hair cortisol as a predictor of depressive symptoms, including the potential for nonlinear relationships.

Methods

A representative community sample of 432 adolescents aged 11 to 17 years was examined. Depressive symptoms were measured using a 9-item short-form of the Center for Epidemiologic Studies-Depression scale. Hair was cut from the posterior vertex region of the scalp using thinning shears. Hair was washed, minced, ground and assayed with Salimetrics® Cortisol Enzyme Immunoassay Kit. Hair cortisol levels were logged for statistical analysis.

Results

In multivariable regression analysis, no significant linear relationship was found in model 1 between hair cortisol and depressive symptoms (b= -0.036, se = 0.02, p = 0.13). In model 2, a marginally significant linear association (b= -0.044, se = 0.02, p-value = 0.06) and a significant curvilinear relationship (b = 0.039, se = 0.01, p-value = 0.005) were found between hair cortisol and depressive symptoms. The results were graphed depicting a u-shaped curve such that hair cortisol levels on the lower and higher end of the distribution predicted depressive symptoms.

Conclusions

The findings highlight the need to consider investigation of nonlinear associations between cortisol and depressive symptoms. Longitudinal mechanistic research is needed to elucidate the causal relationships between hypothalamic-pituitary-adrenal axis dysregulation and depressive symptoms as well as a better understanding of the biological mechanisms through which cortisol may contribute to depressive symptoms and psychopathology.

Introduction

Nearly 1 in 8 U.S. adolescents reported a major depressive episode in 2016, a proportion that has steadily increased over the past decade. (National Institute of Mental Health, 2017). Early identification of depression is vital as suicide is now the second leading cause of death among adolescents aged 11–17 years (Hedegaard et al., 2018). Stress biomarkers, such as cortisol, have been investigated as potential tools to aid in the diagnosis and management of adolescent depression. (Guerry and Hastings, 2011) Hair cortisol may be a particularly useful biomarker to aid in the diagnosis of depression as it provides a longer term and retrospective measure of cortisol with less collection burden than salivary measures (Short et al., 2016).

However, few studies to date have examined hair cortisol as a predictor of depression for any life stage of development, and of those that have, the findings have been mixed (Caparros-Gonzalez et al., 2017; Dowlati et al., 2010; Gerber et al., 2013; Mayer et al., 2018). Specifically, the association between hair cortisol and depression or depressive symptoms was reported as null in adults with coronary artery disease (Dowlati et al., 2010) as well as in young adult medical interns (Mayer et al., 2018); positive in adult pregnant women in which higher hair cortisol levels during the first and third trimester predicted post-partum depression (Caparros-Gonzalez et al., 2017); and negative in a small young adult sample of university students in which higher hair cortisol levels were associated with fewer depressive symptoms (Gerber et al., 2013). Thus, we build on this research through the investigation of hair cortisol as a predictor of depressive symptoms in a representative community sample of youth. We explore both linear and nonlinear associations due to the mixed findings in the literature and findings from prior research in which urinary cortisol levels at both the low and high end of the distribution were associated with increased depressive symptoms in older adults (Penninx et al., 2007).

Section snippets

Study design and sample

The current study examined data from the Adolescent Health and Development in Context (AHDC) study– a longitudinal cohort study investigating the impact of social and spatial exposures on the health of diverse youth aged 11–17 years (n = 1401) in Franklin County, OH; stress biomarkers, including hair cortisol, were collected on a subsample of youth participating in the first wave of the AHDC study (N = 600). The study design is described in detail elsewhere (Ford et al., 2016; Ford and Stowe,

Discussion

This study is among the first to examine linear and nonlinear relationships between cortisol levels in hair and depressive symptoms finding that hair cortisol levels at the lower and higher end of the sample distribution predicted increased depressive symptoms in this large representative sample of youth. These findings are consistent with a study of older adults in which urinary cortisol levels at the low and high end predicted depressive symptoms (Penninx et al., 2007). Together, these

CRediT authorship contribution statement

Jodi L Ford: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Writing - original draft, Writing - review & editing. Samantha J. Boch: Conceptualization, Data curation, Methodology, Writing - review & editing. Christopher R. Browning: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Writing - review & editing.

Declaration of Competing Interest

Drs. Ford, Boch and Browning have no conflicts of interest to disclose.

Acknowledgements

This study was funded by the U.S. National Institutes of Health, National Institute on Drug Abuse (Ford, 1R21DA034960 and Browning, 5R01DA032371) and National Institute of Child Health and Development (Casterline, 2P2CHD058484).

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Wave 1 survey and TL data from the Adolescent Health and Development in Context study were analyzed (N = 995). Depression and anxiety diagnosis were parent-reported measures categorized as: current diagnosis, prior diagnosis, and never diagnosed (reference category). Depressive symptoms were measured via adolescent-report using nine items from the Center for Epidemiologic Studies-Depression scale, short form. Anxiety symptoms were measured via adolescent-report using eight items from the pediatric anxiety scale obtained from the Patient-Reported Outcomes Measurement Information System. Genomic DNA was isolated from 500 μL saliva via ethanol precipitation. Genomic DNA TL was assessed using monoplexed quantitative polymerase chain reactions. Relative T/S quantities were calculated in accordance with established procedures. Covariates included sociodemographic factors (sex, age, race/ethnicity, caregiver marital status and education level, and household income), pubertal development, and season of collection. Descriptive and multivariable linear regression analyses were conducted, including an examination of sex as a moderator in the relationships between depression, anxiety, and TL.
In multivariable analysis, adolescents with a current depression diagnosis (b = −0.26, p < .05), but not a prior diagnosis (b =0.05, p > .05) had shorter TL than those who were never diagnosed; higher depressive symptom scores were associated with shorter TL (b = −0.12, p < .05). No significant associations were found between anxiety diagnosis and TL; however, higher anxiety symptom scores were associated with shorter TL (b = −0.14, p < .01). Sex did not significantly moderate any of the relationships between depression, anxiety and TL.
Depression and anxiety were associated with shorter TL in this diverse community sample of adolescents and the findings highlight the potential for impaired mental health to contribute to cellular senescence as early as adolescence. Prospective research on the long-term effect of depression and anxiety occurring earlier in the life span on TL over time is needed, including examination of potential mechanisms that may accelerate or buffer the negative effects of impaired mental health on TL.
Everyday perceptions of safety and racial disparities in hair cortisol concentration
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Black-White disparities in physiological stress during adolescence are increasingly evident but remain incompletely understood. We examine the role of real-time perceptions of safety in the context of everyday routines to gain insight into the sources of observed adolescent racial differences in chronic stress as measured by hair cortisol concentration (HCC).
We combined social survey, ecological momentary assessment (EMA), and hair cortisol data on 690 Black and White youth ages 11–17 from wave 1 of the Adolescent Health and Development in Context (AHDC) study to investigate racial differences in physiological stress. Individual-level, reliability-adjusted measures of perceived unsafety outside the home were drawn from a week-long smartphone-based EMA and tested for association with hair cortisol concentration.
We observed a statistically significant interaction (p < .05) between race and perceptions of unsafety. For Black youth, perceived unsafety was associated with higher HCC (p < .05). We observed no evidence of an association between perceptions of safety and expected HCC for White youth. For youth who perceive their out-of-home activity locations to be consistently safe, the racial difference in expected HCC was not statistically significant. At the high end of perceived unsafety, however, Black-White differences in HCC were pronounced (0.75 standard deviations at the 95th percentile on perceived unsafety; p < .001).
These findings call attention to the role of everyday perceptions of safety across non-home routine activity contexts in explaining race differences in chronic stress as assessed by hair cortisol concentrations. Future research may benefit from data on in situ experiences to capture disparities in psychological and physiological stress.
The use of biochemical indexes in hair for clinical studies of psychiatric diseases: What can we learn about mental disease from hair?
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Analysis of hair samples provides unique advantages, including non-invasive sampling, sample stability, and the possibility of additional optimization of high sensitivity detection methods. Hair sample analysis is often used in psychiatric disease research to evaluate previous periods of stress encountered by patients. Glucocorticoid analysis is the most frequently tested indicator of stress. Furthermore, the hypothalamus-pituitary-gonad axis and endocannabinoid system also are involved in the occurrence and development of mental disorders. The endocannabinoid and sex hormone levels in patients experiencing mental illness are considerably different from levels observed in healthy individuals. Nevertheless, due to the different methods used to assess the degree of disease and the range of analytical methods involved in clinical research, the trends in changes for these biomarkers are not uniform. The correlations between changes in biomarker concentrations and illness severity also are not clear. The observed alterations suggest these biochemical substances in hair have potential as biomarkers for diagnosis or predictive treatment. However, the variable results obtained thus far could hamper further development of hair samples for clinical assessment in psychiatric disorders. This article summarizes the published reports documenting the changes in the content of relevant substances in hair in individuals experiencing mental illness and the degree of correlation. In the discussion section, we proposed several issues that should be considered in future studies of hair samples obtained from patients with mental disorders to promote the use of hair sample assessment as an aid in diagnosis or predictive treatment.
Pre-pandemic socio-emotional vulnerability, internalizing and externalizing symptoms predict changes in hair cortisol concentrations in reaction to the COVID-19 pandemic in children
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The latter can be divided into two broad categories: internalizing (e.g., depression, anxiety) and externalizing (e.g., disruptive behaviour, attention problems, hyperactivity) symptoms. Indeed, numerous cross-sectional studies have found that altered HCC was associated with internalizing (Ford et al., 2019; Gray et al., 2018; Lu et al., 2018; Rietschel et al., 2016; Sandstrom et al., 2021; Stalder et al., 2017) and externalizing (Grotzinger et al., 2018; Kao et al., 2018; Pauli-Pott et al., 2017, 2019; Schloß et al., 2018; White et al., 2017) symptoms in youth. Nevertheless, findings regarding the directionality of these effects (positive vs. negative) are inconclusive.
The COVID-19 pandemic led to increased distress in many children, particularly in girls. Socio-emotional vulnerability, as well as psychiatric symptomatology prior to or during the initial stages of the pandemic, have been identified as important predictors of this distress. Still, it is unclear whether the pandemic also had physiological repercussions in children. If so, it remains to be determined whether these same predictors could provide insight into inter-individual variability. This longitudinal study aimed to investigate the effects of socio-emotional vulnerability, as well as pre-pandemic internalizing and externalizing symptoms, on hair cortisol concentrations (HCC) in response to the COVID-19 pandemic in healthy youth. In June 2020 (T1), 69 healthy children (M = 11.57 y/o) who visited the laboratory between 2017 and 2019 (T0) provided a 6 cm hair sample. This technique allowed us to quantify cortisol secretion during the three months preceding the COVID-19 pandemic (Segment A) and during the first three months of the first wave of the pandemic in Quebec, Canada (Segment B). At T0, participants completed the Dominic Interactive to assess pre-pandemic internalizing and externalizing symptoms. A socio-emotional composite score (SECS) was derived using a weighted z-score with the following constructs: anxiety sensitivity (Childhood Anxiety Sensitivity Index) measured at T0, trait anxiety (Trait subscale of the State-Trait Anxiety Inventory for Children (STAI-C)), intolerance of uncertainty (Intolerance of Uncertainty Scale for Children), and trait rumination (Children’s Response Style Scale) measured at T1. A linear regression was conducted using the percent change in HCC across Segment A and B as the dependent variable, where SECS, pre-pandemic internalizing and externalizing symptoms, and sex were used as predictors. We found a main effect of sex, with girls presenting increased HCC reactivity compared to boys. We also found that SECS and internalizing symptoms negatively predicted HCC, whereas the opposite relationship was found between externalizing symptoms and HCC reactivity. For healthy children, our results suggest that previous psychiatric symptoms and socio-emotional vulnerability may be risk factors for the presentation of diverging cortisol response patterns in response to an adverse life event (such as the COVID-19 pandemic).
Do subjective and objective measures of stress agree in a clinical sample of youth and their parents?
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Similarly inconsistent findings were reported on the association between HCC and depression, depending on the type of depression (atypical vs melancholic) and the timing of sampling with both low and high levels of HCC associated with depression. Among young adults, HCC has been found to have a negative association with depressive symptoms [24], however, more recent findings have suggested a curvilinear relationship exists such that HCC at the low and high end of the distribution are associated with depressive symptoms [25]. Limited research in children has focused on the association between HCC and posttraumatic stress disorder [26], externalizing disorders [27], and environmental stress from childhood adversities such as maltreatment [28] and chronic physical illness [29].
This study explored agreement and potential relationships among perceived stress (self-reported using the Perceived Stress Scale), hair cortisol concentration (HCC), and mental disorders in a clinical sample of youth and their parents. Data were collected from a cross-sectional sample of 48 youth (38 females; mean age = 15.6 years) with a mental disorder and 72 parents (65 females; mean age = 45.49 years). Agreement was assessed using Bland-Altman plots and intraclass correlation coefficients. Multiple regression was used to model the association between covariates and HCC and perceived stress for youth and parents. Agreement between perceived stress and HCC was low for both youth and parents (ICC = 0.15 to 0.31). Among youth, lower income (β = 0.24) and parent psychopathology (β = 0.42) were associated with higher HCC. Female sex (β = 0.42) and higher parent psychopathology (β = 0.28) were associated with higher perceived stress, whereas chronic physical illness was associated with lower perceived stress (β = −0.24). Among parents, female sex (β = −0.21) was associated with lower HCC and family functioning (β = 0.46) was associated with higher perceived stress. In youth, higher HCC was associated with generalized anxiety (OR = 1.14) and higher perceived stress was associated with major depressive episode (OR = 1.33), generalized anxiety (OR = 1.10), and separation anxiety (OR = 1.14). Among parents, higher HCC was associated with depression (β = 0.27) and perceived stress was associated with depression (β = 0.53) and anxiety (β = 0.45). This exploratory study shows that agreement between psychological and physiological stress is low in a clinical sample of youth and their parents. Sociodemographic and psychosocial factors, and mental health, are differentially associated with psychological and physiological stress.
Longitudinal hair cortisol in low-income young children: A useful biomarker of behavioral symptom change?
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First, the sample size was relatively small, albeit similar to other studies of HCC in low-income children (e.g., Lembcke et al., 2020; Ling et al., 2020; Simmons et al., 2019), and it is the only known study of repeated measures of HCC and behavior problems in young children to examine change. There is some indication that HCC may be related to symptomatology in youth in a non-linear fashion (Ford et al., 2019), and the current study did not have sufficient power to test this possibility. However, the longitudinal HCC data within two understudied, difficult to recruit and retain populations experiencing significant adversity is noteworthy.
Early childhood is a developmental period characterized by significant plasticity, heterogeneity in behaviors and biological functioning. Yet, cumulative cortisol secretion, as measured by hair cortisol, has not been examined longitudinally in relation to change in behavioral problems in young children. The current study examined cross-sectional and longitudinal associations between hair cortisol and changes in behavior problems in a combined sample (N = 88) of two groups of young children from low-income families: 1) A trauma-exposed sample that participated in Child-Parent Psychotherapy (CPP) (n = 43; Mean Age = 4.31, SD = 1.16; 53% Female; 77% Hispanic), and 2) A community sample of children from families experiencing high stress (n = 45; Mean Age = 3.20, SD = 0.29; 67% Female; 58% Hispanic). Cortisol was assayed from hair collected from children at baseline and, on average, one year later. Mothers completed the Child Behavior Checklist at the same time hair samples were collected. Baseline hair cortisol in children was not associated with maternally-reported child behavioral problems at baseline and did not predict change in behavior problems over time. In contrast, increases in cortisol were associated with greater improvement in child behavior problems (b = −2.98, p < 0.05), controlling for group status and relevant covariates. Subgroup analyses showed that cortisol change across one year significantly differed between the two groups (p = 0.043): on average, community children exhibited a decrease, whereas CPP children demonstrated no change. Hair cortisol concentration was similarly related to improvements in mother-reported behavior problems across both CPP and community groups over time. In summary, there were no cross-sectional associations with hair cortisol, whereas increases were associated with improved child well-being. Findings demonstrate an important link between this increasingly common biomarker and child health, but suggest that changes over time may be more informative than cross-sectional associations.

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Hair cortisol and depressive symptoms in youth: An investigation of curvilinear relationships

Highlights

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study design and sample

Discussion

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgements

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Eur. Neuropsychopharmacol.

Am. J. Geriatr. Psychiatry

Horm. Behav.

Psychoneuroendocrinology

Hair cortisol levels, psychological stress and psychopathological symptoms as predictors of postpartum depression

PLoS One