Skip to main content Accessibility help

Developmental pathways from preschool irritability to multifinality in early adolescence: the role of diurnal cortisol

  • Ellen M. Kessel (a1), Allison Frost (a2), Brandon L. Goldstein (a3), Sarah R. Black (a4), Lea R. Dougherty (a5), Gabrielle A. Carlson (a6) and Daniel N. Klein (a2)...



Early irritability predicts a broad spectrum of psychopathology spanning both internalizing and externalizing disorders, rather than any particular disorder or group of disorders (i.e. multifinality). Very few studies, however, have examined the developmental mechanisms by which it leads to such phenotypically diverse outcomes. We examined whether variation in the diurnal pattern of cortisol moderates developmental pathways between preschool irritability and the subsequent emergence of internalizing and externalizing symptoms 9 years later.


When children were 3 years old, mothers were interviewed about children's irritability and completed questionnaires about their children's psychopathology. Six years later, children collected saliva samples at wake-up and bedtime on three consecutive days. Diurnal cortisol patterns were modeled as latent difference scores between evening and morning samples. When children were approximately 12 years old, mothers again completed questionnaires about their children's psychopathology.


Among children with higher levels of irritability at age 3, a steeper diurnal cortisol slope at age 9 predicted greater internalizing symptoms and irritability at age 12, whereas a blunted slope at age 9 predicted greater externalizing symptoms at age 12, adjusting for baseline and concurrent symptoms.


Our results suggest that variation in stress system functioning can predict and differentiate developmental trajectories of early irritability that are relatively more internalizing v. those in which externalizing symptoms dominate in pre-adolescence.


Corresponding author

Author for correspondence: Ellen M. Kessel, E-mail:


Hide All
Achenbach, T. M., McConaughy, S. H., & Howell, C. T. (1987). Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity. Psychological Bulletin, 101(2), 213232.
Achenbach, T. M., & Rescorla, L. (2000). Manual for the ASEBA preschool forms & profiles: An integrated system of multi-informant assessment. Burlington, VT: ASEBA.
Achenbach, T. M., & Rescorla, L. (2001). Manual for the ASEBA school-age forms & profiles: An integrated system of multi-informant assessment. Burlington, VT: ASEBA.
Aiken, L. S., West, S. G., & Reno, R. R. (1991). Multiple regression: Testing and interpreting interactions. Thousand Oaks, California: Sage.
Azar, R., Zoccolillo, M., Paquette, D., Quiros, E., Baltzer, F., & Tremblay, R. E. (2004). Cortisol levels and conduct disorder in adolescent mothers. Journal of the American Academy of Child and Adolescent Psychiatry, 43(4), 461468; discussion 469–472. doi: 10.1097/00004583-200404000-00012.
Beauchaine, T. P., & Constantino, J. N. (2017). Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity. Biomarkers in Medicine 11(9): 769780. doi: 10.2217/bmm-2017-0002.
Bernard, K., Peloso, E., Laurenceau, J. P., Zhang, Z., & Dozier, M. (2015). Examining change in cortisol patterns during the 10-week transition to a new child-care setting. Child Development, 86(2), 456471. doi: 10.1111/cdev.12304.
Brennan, P. A., & Raine, A. (1997). Biosocial bases of antisocial behavior: Psychophysiological, neurological, and cognitive factors. Clinical Psychology Review, 17(6), 589604.
Burt, K. B., & Obradovic, J. (2013). The construct of psychophysiological reactivity: Statistical and psychometric issues. Developmental Review, 33(1), 2957. doi: 10.1016/j.dr.2012.10.002.
Caspi, A., Houts, R. M., Belsky, D. W., Goldman-Mellor, S. J., Harrington, H., Israel, S., … Moffitt, T. E. (2014). The p factor: One general psychopathology factor in the structure of psychiatric disorders? Clinical Psychological Science, 2(2), 119-137. doi: 10.1177/2167702613497473.
Cham, H., Reshetnyak, E., Rosenfeld, B., & Breitbart, W. (2017). Full information maximum likelihood estimation for latent variable interactions with incomplete indicators. Multivariate Behavioral Research, 52(1), 1230. doi: 10.1080/00273171.2016.1245600.
Copeland, W. E., Brotman, M. A., & Costello, E. J. (2015a). Normative irritability in youth: Developmental findings from the great smoky mountains study. Journal of the American Academy of Child and Adolescent Psychiatry, 54(8), 635642. doi: 10.1016/j.jaac.2015.05.008.
Copeland, W. E., Wolke, D., Shanahan, L., & Costello, E. J. (2015b). Adult functional outcomes of common childhood psychiatric problems: A prospective, longitudinal study. JAMA Psychiatry, 72(9), 892899. doi: 10.1001/jamapsychiatry.2015.0730.
Costello, E. J., Copeland, W., & Angold, A. (2011). Trends in psychopathology across the adolescent years: What changes when children become adolescents, and when adolescents become adults? Journal of Child Psychology and Psychiatry and Allied Disciplines, 52(10), 10151025. doi: 10.1111/j.1469-7610.2011.02446.x.
De Bellis, M. D., Dahl, R. E., Perel, J. M., Birmaher, B., Al-Shabbout, M., Williamson, D. E., … (1996). Nocturnal ACTH, cortisol, growth hormone, and prolactin secretion in prepubertal depression. Journal of the American Academy of Child and Adolescent Psychiatry, 35(9), 11301138. doi: 10.1097/00004583-199609000-00010.
Dougherty, L. R., Smith, V. C., Bufferd, S. J., Kessel, E., Carlson, G. A., & Klein, D. N. (2015). Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 56(9), 9991007. doi: 10.1111/jcpp.12403.
Dougherty, L. R., Smith, V. C., Bufferd, S. J., Stringaris, A., Leibenluft, E., Carlson, G. A., & Klein, D. N. (2013). Preschool irritability: Longitudinal associations with psychiatric disorders at age 6 and parental psychopathology. Journal of the American Academy of Child and Adolescent Psychiatry, 52(12), 13041313. doi: 10.1016/j.jaac.2013.09.007.
Edwards, S., Clow, A., Evans, P., & Hucklebridge, F. (2001). Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity. Life Sciences, 68(18), 20932103.
Egger, H. L., & Angold, A. (2006). Common emotional and behavioral disorders in preschool children: Presentation, nosology, and epidemiology. Journal of Child Psychology and Psychiatry and Allied Disciplines, 47(3-4), 313337. doi: 10.1111/j.1469-7610.2006.01618.x.
Egger, H. L., Erkanli, A., Keeler, G., Potts, E., Walter, B. K., & Angold, A. (2006). Test-retest reliability of the Preschool Age Psychiatric Assessment (PAPA). Journal of the American Academy of Child and Adolescent Psychiatry, 45(5), 538549. doi: 10.1097/01.chi.0000205705.71194.b8.
Enders, C. K., & Bandalos, D. L. (2001). The relative performance of full information maximum likelihood estimation for missing data in structural equation models. Structural Equation Modeling, 8(3), 430457. doi: 10.1207/S15328007sem0803_5.
Garvey, M., Avenevoli, S., & Anderson, K. (2016). The national institute of mental health research domain criteria and clinical research in child and adolescent psychiatry. Journal of the American Academy of Child and Adolescent Psychiatry, 55(2), 9398. doi: 10.1016/j.jaac.2015.11.002.
Gerra, G., Zaimovic, A., Avanzini, P., Chittolini, B., Giucastro, G., Caccavari, R., … (1997). Neurotransmitter-neuroendocrine responses to experimentally induced aggression in humans: Influence of personality variable. Psychiatry Research, 66(1), 3343.
Goodyer, I. M., Herbert, J., Tamplin, A., & Altham, P. M. (2000). Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. British Journal of Psychiatry, 177, 499504.
Granger, D. A., Fortunato, C. K., Beltzer, E. K., Virag, M., Bright, M. A., & Out, D. (2012). Focus on methodology: Salivary bioscience and research on adolescence: an integrated perspective. Journal of Adolescence, 35(4), 10811095.
Halligan, S. L., Herbert, J., Goodyer, I., & Murray, L. (2007). Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents. Biological Psychiatry, 62(1), 4046. doi: 10.1016/j.biopsych.2006.09.011.
Hayes, A. F., & Matthes, J. (2009). Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations. Behavior Research Methods, 41(3), 924936. doi: 10.3758/BRM.41.3.924.
Kariyawasam, S. H., Zaw, F., & Handley, S. L. (2002). Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder. Neuroendocrinology Letters, 23(1), 4548.
Kertes, D. A., Gunnar, M. R., Madsen, N. J., & Long, J. D. (2008). Early deprivation and home basal cortisol levels: A study of internationally adopted children. Development and Psychopathology, 20(2), 473491. doi: 10.1017/S0954579408000230.
Kessel, E. M., Meyer, A., Hajcak, G., Dougherty, L. R., Torpey-Newman, D. C., Carlson, G. A., & Klein, D. N. (2016). Transdiagnostic factors and pathways to multifinality: The error-related negativity predicts whether preschool irritability is associated with internalizing versus externalizing symptoms at age 9. Development and Psychopathology, 28(4pt1), 913926. doi: 10.1017/S0954579416000626.
King, D. W., King, L. A., McArdle, J. J., Grimm, K., Jones, R. T., & Ollendick, T. H. (2006). Characterizing time in longitudinal trauma research. Journal of Traumatic Stress, 19(2), 205215. doi: 10.1002/jts.20112.
Klimes-Dougan, B., Hastings, P. D., Granger, D. A., Usher, B. A., & Zahn-Waxler, C. (2001). Adrenocortical activity in at-risk and normally developing adolescents: Individual differences in salivary cortisol basal levels, diurnal variation, and responses to social challenges. Development and Psychopathology, 13(3), 695719.
Koss, K. J., & Gunnar, M. R. (2018). Annual research review: Early adversity, the hypothalamic-pituitary-adrenocortical axis, and child psychopathology. Journal of Child Psychology and Psychiatry, 59(4), 327346. doi: 10.1111/jcpp.12784.
Lahey, B. B., Krueger, R. F., Rathouz, P. J., Waldman, I. D., & Zald, D. H. (2017). A hierarchical causal taxonomy of psychopathology across the life span. Psychological Bulletin, 143(2), 142186. doi: 10.1037/bul0000069.
LeMoult, J., Ordaz, S. J., Kircanski, K., Singh, M. K., & Gotlib, I. H. (2015). Predicting first onset of depression in young girls: Interaction of diurnal cortisol and negative life events. Journal of Abnormal Psychology, 124(4), 850859. doi: 10.1037/abn0000087.
Lok, A., Mocking, R. J., Ruhe, H. G., Visser, I., Koeter, M. W., Assies, J., … (2012). Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression. Psychoneuroendocrinology, 37(7), 892902. doi: 10.1016/j.psyneuen.2011.10.005.
Lopez-Duran, N. L., Kovacs, M., & George, C. J. (2009). Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: A meta-analysis. Psychoneuroendocrinology, 34(9), 12721283. doi: 10.1016/j.psyneuen.2009.03.016.
McArdle, J. J. (2009). Latent variable modeling of differences and changes with longitudinal data. Annual Review of Psychology, 60, 577605. doi: 10.1146/annurev.psych.60.110707.163612.
McBurnett, K., Raine, A., Stouthamer-Loeber, M., Loeber, R., Kumar, A. M., Kumar, M., & Lahey, B. B. (2005). Mood and hormone responses to psychological challenge in adolescent males with conduct problems. Biological Psychiatry, 57(10), 11091116. doi: 10.1016/j.biopsych.2005.01.041.
Moss, H. B., Vanyukov, M. M., & Martin, C. S. (1995). Salivary cortisol responses and the risk for substance abuse in prepubertal boys. Biological Psychiatry, 38(8), 547555. doi: 10.1016/0006-3223(94)00382-D.
Mulraney, M., Melvin, G., & Tonge, B. (2014). Brief report: Can irritability act as a marker of psychopathology? Journal of Adolescence, 37(4), 419-423. doi: 10.1016/j.adolescence.2014.03.005.
Nolen-Hoeksema, S., & Watkins, E. R. (2011). A heuristic for developing transdiagnostic models of psychopathology: Explaining multifinality and divergent trajectories. Perspectives on Psychological Science, 6(6), 589609. doi: 10.1177/1745691611419672.
Olino, T. M., Dougherty, L. R., Bufferd, S. J., Carlson, G. A., & Klein, D. N. (2014). Testing models of psychopathology in preschool-aged children using a structured interview-based assessment. Journal of Abnormal Child Psychology, 42(7), 12011211. doi: 10.1007/s10802-014-9865-x.
Pajer, K., Gardner, W., Rubin, R. T., Perel, J., & Neal, S. (2001). Decreased cortisol levels in adolescent girls with conduct disorder. Archives of General Psychiatry, 58(3), 297302.
Platje, E., Jansen, L. M., Raine, A., Branje, S. J., Doreleijers, T. A., de Vries-Bouw, M., … Vermeiren, R. R. (2013). Longitudinal associations in adolescence between cortisol and persistent aggressive or rule-breaking behavior. Biological Psychology, 93(1), 132137. doi: 10.1016/j.biopsycho.2013.01.002.
Riglin, L., Eyre, O., Cooper, M., Collishaw, S., Martin, J., Langley, K., … Thapar, A. (2017). Investigating the genetic underpinnings of early-life irritability. Translational Psychiatry, 7(9), e1241. doi: 10.1038/tp.2017.212.
Ruttle, P. L., Shirtcliff, E. A., Serbin, L. A., Fisher, D. B., Stack, D. M., & Schwartzman, A. E. (2011). Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: Longitudinal and concurrent associations with cortisol. Hormones and Behavior, 59(1), 123132. doi: 10.1016/j.yhbeh.2010.10.015.
Salis, K. L., Bernard, K., Black, S. R., Dougherty, L. R., & Klein, D. (2016). Examining the concurrent and longitudinal relationship between diurnal cortisol rhythms and conduct problems during childhood. Psychoneuroendocrinology, 71, 147154. doi: 10.1016/j.psyneuen.2016.05.021.
Shirtcliff, E. A., & Essex, M. J. (2008). Concurrent and longitudinal associations of basal and diurnal cortisol with mental health symptoms in early adolescence. Developmental Psychobiology, 50(7), 690703. doi: 10.1002/dev.20336.
Shirtcliff, E. A., Granger, D. A., Booth, A., & Johnson, D. (2005). Low salivary cortisol levels and externalizing behavior problems in youth. Development and Psychopathology, 17(1), 167184.
Smyth, J. M., Ockenfels, M. C., Gorin, A. A., Catley, D., Porter, L. S., Kirschbaum, C., … Stone, A. A. (1997). Individual differences in the diurnal cycle of cortisol. Psychoneuroendocrinology, 22(2), 89105.
Stringaris, A., Goodman, R., Ferdinando, S., Razdan, V., Muhrer, E., Leibenluft, E., & Brotman, M. A. (2012). The affective reactivity Index: A concise irritability scale for clinical and research settings. Journal of Child Psychology and Psychiatry, 53(11), 11091117. doi: 10.1111/j.1469-7610.2012.02561.x.
Stringaris, A., & Taylor, E. A. (2015). Disruptive mood: Irritability in children and adolescents. NY, New York: Oxford University Press.
van Bokhoven, I., Van Goozen, S. H., van Engeland, H., Schaal, B., Arseneault, L., Seguin, J. R., … Tremblay, R. E. (2005). Salivary cortisol and aggression in a population-based longitudinal study of adolescent males. Journal of Neural Transmission, 112(8), 10831096. doi: 10.1007/s00702-004-0253-5.
Vidal-Ribas, P., Brotman, M. A., Valdivieso, I., Leibenluft, E., & Stringaris, A. (2016). The status of irritability in psychiatry: a conceptual and quantitative review. Journal of the American Academy of Child & Adolescent Psychiatry, 55(7), 556570.
Wakschlag, L. S., Choi, S. W., Carter, A. S., Hullsiek, H., Burns, J., McCarthy, K., … Briggs-Gowan, M. J. (2012). Defining the developmental parameters of temper loss in early childhood: Implications for developmental psychopathology. Journal of Child Psychology and Psychiatry, 53(11), 10991108. doi: 10.1111/j.1469-7610.2012.02595.x.
Wakschlag, L. S., Estabrook, R., Petitclerc, A., Henry, D., Burns, J. L., Perlman, S. B., … Briggs-Gowan, M. L. (2015). Clinical implications of a dimensional approach: The normal: Abnormal Spectrum of early irritability. Journal of the American Academy of Child and Adolescent Psychiatry, 54(8), 626634. doi: 10.1016/j.jaac.2015.05.016.
Wakschlag, L. S., Perlman, S. B., Blair, R. J., Leibenluft, E., Briggs-Gowan, M. J., & Pine, D. S. (2018). The neurodevelopmental basis of early childhood disruptive behavior: Irritable and callous phenotypes as exemplars. American Journal of Psychiatry, 175(2), 114130. doi: 10.1176/appi.ajp.2017.17010045.


Type Description Title
Supplementary materials

Kessel et al. supplementary material
Kessel et al. supplementary material

 Word (23 KB)
23 KB

Developmental pathways from preschool irritability to multifinality in early adolescence: the role of diurnal cortisol

  • Ellen M. Kessel (a1), Allison Frost (a2), Brandon L. Goldstein (a3), Sarah R. Black (a4), Lea R. Dougherty (a5), Gabrielle A. Carlson (a6) and Daniel N. Klein (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.