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

Abstract

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.adolescence | gender differences M ajor depressive disorder (MD) is a serious mental health problem predicted to be the leading health burden worldwide by 2030 (1, 2). MD increases markedly during adolescence and young adulthood: 25% of lifetime mood disorders appear by 18 y of age and 50% by the age of 30 y (3). MD in childhood or adolescence raises the risk of future episodes in adulthood some fourfold (4), especially in adolescent boys and younger men aged 15-35 y (5, 6). The sex ratio for depression is about equal in childhood, but, by the end of adolescence, females outnumber males by a factor of around two to one (7,8). Whether there are underlying mechanisms associated with the emergence of MD during adolescence that are themselves sex-specific is unknown. If this distinction were so, then biomarkers for MD might themselves be preferentially activated in one sex compared with another.Current diagnostic classifications [e.g., the Diagnostic and Statistical Manual for Mental Disorders (DSM) and the International Classification of Diseases (ICD)] have proved to have low diagnostic validity for investigations on the etiology, prevention, or treatment of MD partly because they ignore heterogeneity (9). Identifying predictive biomarkers (10) has been hampered by this variation because the current taxonomic systems may conflate disorders of similar clinical phenotype that have distinctly different aetiologies (11)(12)(13)(14). One approach to t...

Low levels of morning salivary α-amylase activity predict higher number of depressive symptoms in a community sample of children

“…This result was entirely unexpected, as it contradicts some of the previous scientific literature on this issue. Nevertheless, this unexpected result could represent a promising finding in this field of research since recent epidemiological studies have suggested some limitations of morning salivary cortisol levels in predicting high risk of developing initial MDE onset in young adult females (Owens et al, 2014). According to our results, it is probable that sAA could overcome this limitation in future studies.…”

“…Although the studies reviewed in the previous paragraphs highlight the usefulness of cortisol in particular (especially when it is measured in form of the CAR) as an early predictor of a future triggering of a first MDE in adolescents (without gender differences in the majority of the reviewed studies), a recent and robust epidemiological study that examined a wide cohort showed that the predictive capacity of morning cortisol levels could be influenced by gender, thereby increasing misunderstanding of these initial results (Owens et al, 2014). Specifically, these researchers observed that in the total sample of 1858 participants, morning cortisol was associated with a high risk of depression exclusively in male participants.…”

“…Specifically, these researchers observed that in the total sample of 1858 participants, morning cortisol was associated with a high risk of depression exclusively in male participants. Given the higher prevalence of depression in adolescent girls (Domench-Llaberia et al, 2009;FonsecaPedrero, Paino, Lemos-Giráldez, & Muñiz, 2011;Mendes et al, 2012;Weissman et al, 2006), these groups of results (Lewis, Jones, & Goodyer, 2016;Nelemans et al, 2014;Owens et al, 2014) should alert us of the need to shift the focus of our attention towards the search for further sensitive biomarkers of early depression risk in girls. In line with this search for new, more precise biological markers of depression, the usefulness of sAA as a low-cost, biological marker of psychopathology has become a relevant new line of research, especially over the two last decades.…”

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

“…McEwen, 2012McEwen, , 2013. These results are also of interest in relation to evidence relating levels of post awakening cortisol secretion as a risk factor for future psychopathology (Halligan et al, 2007;Mannie et al, 2007;Owens et al, 2014).…”

Reduction in adolescent depression after contact with mental health services: a longitudinal cohort study in the UK

“…13,14 Additionally, MFQ scores above the 75th percentile are an established behavioural marker for clinical diagnosis of major depression. 22 The Youdin Index was calculated to determine the clinical cutoff point, because it maximises sensitivity and specifi city, 23 thereby increasing correct classifi cation of individuals with and without depression.…”