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

Significance Clinical depression is a severe and common illness, characterized primarily by persistent low mood and lack of pleasure in usually enjoyable activities, that results in significant impairment in everyday living. It also involves alterations in cognitive and hormonal functions. There is substantial variation between depressed individuals in terms of the causes and therapeutic response, making it difficult to identify those most likely to benefit from intervention and treatment. We derived subtypes of adolescents in the population based on different levels of the hormone cortisol and subclinical depressive symptoms. A group (17%) with both high levels of cortisol and depressive symptoms of both sexes had more depressed thinking. Boys in this group were at high risk for clinical depression. 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.

[1]  Domján Andrea,et al.  World Medical Association Declaration of Helsinki (WMA) - Ethical principles for medical research involving human subjects , 2014 .

[2]  S. M. Stahl,et al.  Innovative solutions to novel drug development in mental health , 2013, Neuroscience & Biobehavioral Reviews.

[3]  A. Calder,et al.  Research Review: Evaluating and reformulating the developmental taxonomic theory of antisocial behaviour , 2013, Journal of child psychology and psychiatry, and allied disciplines.

[4]  E. Sonuga-Barke.  The challenge of mapping diagnostic categories onto developmental pathophysiology: DSM-6 anyone? , 2013, Journal of child psychology and psychiatry, and allied disciplines.

[5]  Ronan A Lyons,et al.  UK health performance: findings of the Global Burden of Disease Study 2010 , 2013, BDJ.

[6]  Richard D Riley,et al.  Prognosis research strategy (PROGRESS) 4: Stratified medicine research , 2013, BMJ : British Medical Journal.

[7]  P. Lewinsohn,et al.  Key Characteristics of Major Depressive Disorder Occurring in Childhood, Adolescence, Emerging Adulthood, and Adulthood , 2013, Clinical psychological science : a journal of the Association for Psychological Science.

[8]  T. Dalgleish,et al.  Enhancing Autobiographical Memory Specificity Through Cognitive Training , 2013 .

[9]  Peter B. Jones,et al.  Adult mental health disorders and their age at onset , 2013, British Journal of Psychiatry.

[10]  W. Cullen,et al.  Research confuses me: what is the difference between case-control and cohort studies in quantitative research? , 2013, Irish medical journal.

[11]  P. Dayan,et al.  Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis , 2013, Biology of Mood & Anxiety Disorders.

[12]  Tim Croudace,et al.  5-HTTLPR and Early Childhood Adversities Moderate Cognitive and Emotional Processing in Adolescence , 2012, PloS one.

[13]  Richard J. Davidson,et al.  Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence , 2012, Nature Neuroscience.

[14]  R. Araya,et al.  Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial , 2012, BMJ : British Medical Journal.

[15]  N. Kalin,et al.  Longitudinal stability and developmental properties of salivary cortisol levels and circadian rhythms from childhood to adolescence. , 2012, Developmental psychobiology.

[16]  J. Herbert,et al.  Cortisol and depression: three questions for psychiatry , 2012, Psychological Medicine.

[17]  Deepti R. Bathula,et al.  Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD , 2012, Proceedings of the National Academy of Sciences.

[18]  Edward T. Bullmore,et al.  Drug research: A plan for mental illness , 2012, Nature.

[19]  K. Stark,et al.  Structure and measurement of depression in youths: applying item response theory to clinical data. , 2011, Psychological assessment.

[20]  Tim Croudace,et al.  Depressive symptoms during adolescence: comparison between epidemiological and high risk sampling , 2011, Social Psychiatry and Psychiatric Epidemiology.

[21]  Ned H Kalin,et al.  Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence , 2011, Development and Psychopathology.

[22]  Kymberly D. Young,et al.  Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall. , 2011, Behavioral neuroscience.

[23]  Peter B. Jones,et al.  Profiles of family-focused adverse experiences through childhood and early adolescence: The ROOTS project a community investigation of adolescent mental health , 2011, BMC psychiatry.

[24]  P. Hastings,et al.  In Search of HPA Axis Dysregulation in Child and Adolescent Depression , 2011, Clinical child and family psychology review.

[25]  G. Miller,et al.  Depression and Hypothalamic-Pituitary-Adrenal Activation: A Quantitative Summary of Four Decades of Research , 2011, Psychosomatic medicine.

[26]  D. Giussani,et al.  Sex Differences in the Ovine Fetal Cortisol Response to Stress , 2011, Pediatric Research.

[27]  N. Ryan,et al.  Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes. , 2010, The American journal of psychiatry.

[28]  T. Insel,et al.  Wesleyan University From the SelectedWorks of Charles A . Sanislow , Ph . D . 2010 Research Domain Criteria ( RDoC ) : Toward a New Classification Framework for Research on Mental Disorders , 2018 .

[29]  C. Kennard,et al.  A UK strategy for mental health and wellbeing , 2010, The Lancet.

[30]  Nestor L. Lopez-Duran,et al.  Prodromal symptoms and atypical affectivity as predictors of major depression in juveniles: implications for prevention. , 2010, Journal of child psychology and psychiatry, and allied disciplines.

[31]  Tim Croudace,et al.  Cohort Profile: Risk patterns and processes for psychopathology emerging during adolescence: the ROOTS project , 2010, International journal of epidemiology.

[32]  S. Hyman,et al.  The diagnosis of mental disorders: the problem of reification. , 2010, Annual review of clinical psychology.

[33]  C. Otte,et al.  Effects of acute cortisol administration on autobiographical memory in patients with major depression and healthy controls , 2010, Psychoneuroendocrinology.

[34]  Stephanie T. Lanza,et al.  Latent Class and Latent Transition Analysis: With Applications in the Social, Behavioral, and Health Sciences , 2009 .

[35]  Linda M. Collins,et al.  Latent class and latent transition analysis , 2009 .

[36]  M. Ban,et al.  Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents , 2009, British Journal of Psychiatry.

[37]  I. Goodyer,et al.  Treated depression in adolescents: predictors of outcome at 28 weeks. , 2009, The British journal of psychiatry : the journal of mental science.

[38]  I. Goodyer.  Emanuel Miller Lecture: early onset depressions--meanings, mechanisms and processes. , 2008, Journal of child psychology and psychiatry, and allied disciplines.

[39]  A. Beck.  The evolution of the cognitive model of depression and its neurobiological correlates. , 2008, The American journal of psychiatry.

[40]  Peter B. Jones,et al.  A Longitudinal Typology of Symptoms of Depression and Anxiety Over the Life Course , 2007, Biological Psychiatry.

[41]  B. Muthén,et al.  Deciding on the Number of Classes in Latent Class Analysis and Growth Mixture Modeling: A Monte Carlo Simulation Study , 2007 .

[42]  J. Fairbank,et al.  The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. , 2007, Archives of general psychiatry.

[43]  T. Dalgleish,et al.  Autobiographical Memory Specificity and Emotional Disorder , 2007, Psychological bulletin.

[44]  B. Birmaher,et al.  Criterion validity of the Mood and Feelings Questionnaire for depressive episodes in clinic and non-clinic subjects. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[45]  I. Goodyer,et al.  Longitudinal investigation into childhood-and adolescence-onset depression: Psychiatric outcome in early adulthood , 2006, British Journal of Psychiatry.

[46]  Luke Clark,et al.  Mood-congruent bias in affective go/no-go performance of unmedicated patients with major depressive disorder. , 2005, The American journal of psychiatry.

[47]  Ian M Goodyer,et al.  Selected executive skills in adolescents with recent first episode major depression. , 2005, Journal of child psychology and psychiatry, and allied disciplines.

[48]  T. Barnhofer,et al.  Specificity of autobiographical memories and basal cortisol levels in patients with major depression , 2005, Psychoneuroendocrinology.

[49]  B. Kudielka,et al.  Sex differences in HPA axis responses to stress: a review , 2005, Biological Psychology.

[50]  J. Teasdale,et al.  Effects of induced rumination and distraction on mood and overgeneral autobiographical memory in adolescent Major Depressive Disorder and controls. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[51]  J. Teasdale,et al.  Categoric overgeneral autobiographical memory in adolescents with major depressive disorder , 2002, Psychological Medicine.

[52]  J. Grice.  Computing and evaluating factor scores , 2001 .

[53]  L. Wichstrøm,et al.  Depressive symptoms among young Norwegian adolescents as measured by The Mood and Feelings Questionnaire (MFQ) , 2001, European Child & Adolescent Psychiatry.

[54]  D. Rubin,et al.  Testing the number of components in a normal mixture , 2001 .

[55]  M. Gunnar,et al.  Low cortisol and a flattening of expected daytime rhythm: Potential indices of risk in human development , 2001, Development and Psychopathology.

[56]  Florian Holsboer,et al.  The Corticosteroid Receptor Hypothesis of Depression , 2000, Neuropsychopharmacology.

[57]  I. Goodyer,et al.  First-episode major depression in adolescents. Affective, cognitive and endocrine characteristics of risk status and predictors of onset. , 2000, The British journal of psychiatry : the journal of mental science.

[58]  T. Robbins,et al.  Emotional bias and inhibitory control processes in mania and depression , 1999, Psychological Medicine.

[59]  P. Bentler,et al.  Cutoff criteria for fit indexes in covariance structure analysis : Conventional criteria versus new alternatives , 1999 .

[60]  D. Pine,et al.  Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder? , 1999, The American journal of psychiatry.

[61]  E J Costello,et al.  Puberty and depression: the roles of age, pubertal status and pubertal timing , 1998, Psychological Medicine.

[62]  Phil A. Silva,et al.  Development of depression from preadolescence to young adulthood: emerging gender differences in a 10-year longitudinal study. , 1998, Journal of abnormal psychology.

[63]  P Vostanis,et al.  Detection of major and minor depression in children and adolescents: evaluation of the Mood and Feelings Questionnaire. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[64]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[65]  I. Goodyer,et al.  Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age. , 1996, The Journal of clinical endocrinology and metabolism.

[66]  A. Raftery.  Bayesian Model Selection in Social Research , 1995 .

[67]  E. Costello,et al.  Scales to assess child and adolescent depression: checklists, screens, and nets. , 1988, Journal of the American Academy of Child and Adolescent Psychiatry.

[68]  J. Williams,et al.  Autobiographical memory in suicide attempters. , 1986, Journal of abnormal psychology.

[69]  S. Holm.  A Simple Sequentially Rejective Multiple Test Procedure , 1979 .