Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms

Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys