Elevated concentrations of the stress hormone cortisol in hair could potentially predict depressive symptoms in teenagers, but this relationship is not necessarily linear, new research suggests.

A study that included more than 400 adolescents linked cortisol levels to a greater risk for depression. Investigators also found a relationship between lower cortisol levels and other psychiatric conditions.

"The most surprising finding actually was that both the cortisol levels at the low end and the high end of the distribution were correlated with depressive symptoms," lead author Jodi Ford, PhD, RN, associate professor and director of the Stress Science Lab at the Ohio State University College of Nursing in Columbus, told Medscape Medical News.

The findings were published online in Psychoneuroendocrinology.

First Study of Its Kind

Major depression is a risk factor for suicide, which is the second leading cause of death among American youth aged 11 to 17. Nearly one in 8 youths in the US reported a major depressive episode in 2016, a rate that has been increasing over the last decade.

Better biomarkers may improve identification and management of adolescent depression.

Cortisol is a steroid hormone that is continuously released by the hypothalamic–pituitary–adrenal axis (HPA) into the circulatory system. Hair can provide a retrospective and longer-term measure of the mean cortisol level, compared to saliva, which needs to be collected more frequently, said Ford.

As reported by Medscape Medical News, previous research has evaluated hair cortisol as a potential marker of chronic stress, childhood trauma and poor cognition, and even treatment efficacy.

However, previous studies showed mixed evidence on the relationship between hair cortisol and depressive symptoms. The current study, investigators note, is the first to examine cortisol levels as a predictor for depression in youth.

The study included a community sample of 432 teenagers (aged 11 to 17 years old) from the 1401 participants in the ongoing Adolescent Health and Development in Context (AHDC) trial.

The AHDC was a longitudinal cohort study investigating the impact of social and spatial exposures on the health of a diverse group of adolescents in Franklin County, Ohio.

Investigators assessed depressive symptoms using a 10-item short-form version of the Center for Epidemiologic Studies-Depression (CESD) scale.

The questionnaire asked the teens to describe their depressive symptoms experienced in the prior week and provided four possible responses that ranged from "rarely/none of the time/1 day" to "most/all of the time/5-7 days." As the positive-affect symptoms were reverse-coded, higher scores indicated more depressive symptoms.

After asking the teenagers about their hair care practices, including washing frequency, chemical treatments, and product use, the researchers used thinning shears to cut up to 3 cm of hair samples close to the scalp. They then assayed the hair samples to measure mean cortisol levels.

Study control measures included youth-reported age, race and ethnicity, hair care practices, and pubertal development. Caregiver-reported measures included marital status, annual household income, youth use of selected serotonin reuptake inhibitors (SSRIs), and if the youth was ever diagnosed with depression.

Objective measures included season of data collection, body mass index, and assayed hair length (1 cm to <3 cm, >3 cm and 3 cm reference).

U-Shaped Relationship

In multivariable regression analysis, no significant linear relationship was found between hair cortisol and depressive symptoms (b = -0.036, se = .02, P = .13).

A marginally significant linear association (b = -0.044, se = .02, P = .06) and a significant curvilinear relationship (b = .039, se = .01, P = .005) were found between hair cortisol and depressive symptoms.

These results, when graphed, showed a u-shaped curve. Hair cortisol levels on the lower and higher end of the distribution predicted depressive symptoms in a diverse sample of youth.

These results were consistent with a 2007 study in which urinary cortisol levels at the low end and high end predicted depressive symptoms in older adults.

The researchers concluded that more longitudinal research is necessary to better understand the nonlinear associations between cortisol and depressive symptoms; potential causal relationships between HPA dysregulation and depressive symptoms; and the biological mechanisms by which cortisol might contribute to depressive symptoms and psychopathology.

Particularly, they propose that further research needs to focus on younger participants as the majority of prior studies were on adults — and half of lifetime mental health disorders have an onset by age 14.

The researchers acknowledged that no current norms exist for determining hair cortisol levels, which limits its clinical utility as a biomarker.

Another study finding showed that family support could help kids with depression.

"The kids who had reported higher levels of family support had lower depressive symptoms. I think a lot of parents feel sometimes left out as their kids get older, but recognizing how much their support means to their kids really does matter and helps them a lot," said Ford.

Tree Rings

Commenting on the study for Medscape Medical News, Ian H. Gotlib, PhD, professor and director of the Stanford Neurodevelopment, Affect, and Psychopathology Laboratory at Stanford University in California, said that understanding the relationship between stress and depression is an important goal.

However, he cautioned that the investigators measured cortisol at different time points.

He also noted that the presence of sadness or despondency — and how these factors are measured — can change outcomes.

In addition, Gotlib was concerned that the investigators assessed depression using the 10-item CESD questionnaire.

"So they didn't really measure depression as a diagnosis. They measured depression as symptoms. So it's not depression in the psychiatric sense," added Gotlib, who was not involved with the current study.

Cortisol can remain in hair for months, Gotlib noted. Every centimeter of hair accumulates roughly a month's worth of cortisol, which is rather like "tree rings," he said.

As months pass, cortisol dissipates and can be further affected by bleach and other hair products.

"But [hair] is reasonably close to other measures of cortisol, like saliva and blood," Gotlib said.

He was also concerned that although the researchers measured approximately 3 months of cortisol deposition, they only assessed depressive symptoms for 2 weeks.

Gotlib emphasized that the study addressed an important question and the complexity of the association between cortisol and depression "is important to follow up."

The research was funded by the US National Institutes of Health, The National Institute on Drug Abuse, and National Institute of Child Health and Development. Ford and Gotlib have disclosed no relevant financial relationships.

Psychoneuroendocrinology. Published online July 8, 2019. Abstract

For more Medscape Psychiatry news, join us on Facebook and Twitter