Researchers have identified the first biomarker for identifying those adolescent boys at risk for clinical or major depression (MD). The combination of high self-reported depressive symptoms and elevated morning cortisol increase the risk of MD by up to 14 times, according to a study published online Feb. 18 in Proceedings of the National Academy of Sciences. Early identification of this subtype of boys may lead to earlier diagnosis and treatment as MD in childhood, teen, or young adult years substantially raises the risk of episodes of depression later in life. In the study, self-reported depressive symptoms were measured using the 33-item version of the Moods and Feelings Questionnaire, while cortisol was measured by ELISA on 20-μl saliva samples without extraction. One cohort (n = 660) provided four early-morning samples on schooldays within a week and then again 12 months later, and depressive symptoms were measured at baseline, four months, eight months, and 12 months. The second cohort (n = 1,198) provided early-morning samples over three school days and measured depressive symptoms at baseline, 18 months, and 36 months. The researchers utilized these repeated measures of self-reported depressive symptoms and early-morning levels of cortisol (both known correlates to MD) to categorize the young participants (12 years to 19 years of age) from both cohorts into four classes: Class 1, low morning-cortisol levels and low depressive symptoms over time (31 percent); Class 2, low levels of depressive symptoms but relatively high morning cortisol (27 percent); Class 3, high depressive symptoms and low morning cortisol (25 percent); and Class 4, high levels of both morning cortisol and depressive symptoms (17 percent). “We provide clear cut confirmatory evidence for longitudinal stability of morning cortisol levels,” write the authors, led by Matthew Owens, from the University of Cambridge in the United Kingdom. “This finding demonstrates a trait-like property, a key pre requisite for acting as a physiological biomarker.” The researchers found that Class 4 characterization (high morning cortisol and high depressive symptoms) was associated with increased levels of impaired autobiographical memory recall in both sexes but was tied to a greater likelihood of MD in boys only. Participants in Class 2 to Class 4 were more likely to have reported MD at follow-up, compared with Class 1. The odds of being diagnosed with MD increased progressively across the classes from 1.6 to 7.1 (only Class 3 and 4 were significant). For boys in Class 4 versus Class 1, the odds of being clinically depressed was 14.7. “The clinical specificity of these findings for MD was enhanced by the fact that there was no specific association between being a member of class 4 for either sex and the presence of nondepressive psychiatric disorder or, more specifically, behavior disorder,” write the authors. Takeaway: While further validation is needed before such a test can be clinically used, the researchers are encouraged at the prospect of having an objective, quantifiable measure of depression risk, rather than an exclusive reliance on patients’ self-reports.