Skip to main content Accessibility help

The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure

  • Carly E. Herbison (a1), Karina Allen (a1) (a2) (a3), Monique Robinson (a1), John Newnham (a1) and Craig Pennell (a1)...


There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception/pregnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.


Corresponding author

Address correspondence and reprint requests to: Carly E. Herbison, School of Women's and Infants’ Health (M550), University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; E-mail:


Hide All

The first author (C.H.) was supported by scholarships from the Australian Government, Raine Study, and Women and Infants Research Foundation. We thank Dr. Anne Smith and Dr. Garth Kendall for advice using PROC TRAJ in SAS. In addition, we thank the Raine Study participants who took part in each aspect of this research, the Raine Study Team for cohort coordination and data collection, and the National Health and Medical Research Council (NHMRC) and the Telethon Kids Institute for their longstanding funding and support of the study. Core funding for the Western Australian Pregnancy Cohort (Raine) Study is provided by the Raine Medical Research Foundation; University of Western Australia, Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women and Infants Research Foundation; Edith Cowan University; and Curtin University.



Hide All
Ansell, E. B., Rando, K., Tuit, K., Guarnaccia, J., & Sinha, R. (2012). Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions. Biological Psychiatry, 72, 5764. doi:10.1016/j.biopsych.2011.11.022
Australian Bureau of Statistics. (2006). Socio-Economic Indexes for Areas (SEIFA) (Technical Paper 2039.0.55.001) . Canberra: Author.
Australian Bureau of Statistics. (2009). National Survey of Mental Health and Wellbeing: Summary of Results, 4326.0, 2007. Canberra: Author.
Beijers, R., Buitelaar, J. K., & de Weerth, C. (2014). Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: Beyond the HPA axis. European Child and Adolescent Psychiatry, 23, 943956. doi:10.1007/s00787-014-0566-3
Boardman, J. D., & Alexander, K. B. (2011). Stress trajectories, health behaviors, and the mental health of black and white young adults. Social Science and Medicine, 72, 16591666. doi:10.1016/j.socscimed.2011.03.024
Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective Disorders, 82, 217225. doi:10.1016/j.jad.2003.12.013
Cole, D. A., Nolen-Hoeksema, S., Girgus, J., & Paul, G. (2006). Stress exposure and stress generation in child and adolescent depression: A latent trait-state-error approach to longitudinal analyses. Journal of Abnormal Psychology, 115, 4051. doi:10.1037/0021-843X.115.1.40
Conradt, E., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013). The roles of DNA methylation of NR3C1 and 11beta-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics, 8, 13211329. doi:10.4161/epi.26634
Crawford, J. R., & Henry, J. D. (2003). The Depression Anxiety Stress Scales (DASS): Normative data and latent structure in a large non-clinical sample. British Journal of Clinical Psychology, 42(Pt. 2), 111131. doi:10.1348/014466503321903544
Davis, E. P., Glynn, L. M., Waffarn, F., & Sandman, C. A. (2011). Prenatal maternal stress programs infant stress regulation. Journal of Child Psychology and Psychiatry, 52, 119129. doi:10.1111/j.1469-7610.2010.02314.x
Davis, E. P., & Sandman, C. A. (2010). The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Development, 81, 131148. doi:10.1111/j.1467-8624.2009.01385.x
de Bruijn, A. T., van Bakel, H. J., & van Baar, A. L. (2009). Sex differences in the relation between prenatal maternal emotional complaints and child outcome. Early Human Development, 85, 319324. doi:10.1016/j.earlhumdev.2008.12.009
DiPietro, J. A., Novak, M. F., Costigan, K. A., Atella, L. D., & Reusing, S. P. (2006). Maternal psychological distress during pregnancy in relation to child development at age two. Child Development, 77, 573587. doi:10.1111/j.1467-8624.2006.00891.x
DiPietro, J. A., & Voegtline, K. M. (2017). The gestational foundation of sex differences in development and vulnerability. Neuroscience, 342, 420. doi:10.1016/j.neuroscience.2015.07.068
Entringer, S., Buss, C., Shirtcliff, E. A., Cammack, A. L., Yim, I. S., Chicz-DeMet, A., … Wadhwa, P. D. (2010). Attenuation of maternal psychophysiological stress responses and the maternal cortisol awakening response over the course of human pregnancy. Stress, 13, 258268. doi:10.3109/10253890903349501
Espejo, E. P., Hammen, C. L., Connolly, N. P., Brennan, P. A., Najman, J. M., & Bor, W. (2007). Stress sensitization and adolescent depressive severity as a function of childhood adversity: A link to anxiety disorders. Journal of Abnormal Child Psychology, 35, 287299. doi:10.1007/s10802-006-9090-3
Francis, J. L., Moitra, E., Dyck, I., & Keller, M. B. (2012). The impact of stressful life events on relapse of generalized anxiety disorder. Depression and Anxiety, 29, 386391. doi:10.1002/da.20919
Frodl, T., & O'Keane, V. (2013). How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans. Neurobiology of Disease, 52, 2437. doi:10.1016/j.nbd.2012.03.012
Giedd, J. N., Snell, J. W., Lange, N., Rajapakse, J. C., Casey, B. J., Kozuch, P. L., … Rapoport, J. L. (1996). Quantitative magnetic resonance imaging of human brain development: Ages 4–18. Cerebral Cortex, 6, 551560.
Glover, V., & Hill, J. (2012). Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: An evolutionary perspective. Physiology & Behavior, 106, 736740. doi:10.1016/j.physbeh.2012.02.011
Gluckman, P. D., & Hanson, M. A. (2006). The developmental origins of health and disease: An overview. In Gluckman, P. D. & Hanson, M. A. (Eds.), Developmental origins of health and disease (pp. 15). Cambridge: Cambridge University Press.
Gluckman, P. D., Hanson, M. A., Morton, S. M., & Pinal, C. S. (2005). Life-long echoes—A critical analysis of the developmental origins of adult disease model. Biology of the Neonate, 87, 127139. doi:10.1159/000082311
Goel, N., & Bale, T. L. (2009). Examining the intersection of sex and stress in modelling neuropsychiatric disorders. Journal of Neuroendocrinology, 21, 415420. doi:10.1111/j.1365-2826.2009.01843.x
Goodman, E., Slap, G. B., & Huang, B. (2003). The public health impact of socioeconomic status on adolescent depression and obesity. American Journal of Public Health, 93, 18441850.
Gunnar, M. R., Frenn, K., Wewerka, S. S., & Van Ryzin, M. J. (2009). Moderate versus severe early life stress: Associations with stress reactivity and regulation in 10–12-year-old children. Psychoneuroendocrinology, 34, 6275. doi:10.1016/j.psyneuen.2008.08.013
Hammen, C., Henry, R., & Daley, S. E. (2000). Depression and sensitization to stressors among young women as a function of childhood adversity. Journal of Consulting and Clinical Psychology, 68, 782787.
Hammen, C., Kim, E. Y., Eberhart, N. K., & Brennan, P. A. (2009). Chronic and acute stress and the prediction of major depression in women. Depression and Anxiety, 26, 718723. doi:10.1002/da.20571
Hazel, N. A., Hammen, C., Brennan, P. A., & Najman, J. (2008). Early childhood adversity and adolescent depression: The mediating role of continued stress. Psychological Medicine, 38, 581589. doi:10.1017/S0033291708002857
Heim, C., & Binder, E. B. (2012). Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Experimental Neurology, 233, 102111. doi:10.1016/j.expneurol.2011.10.032
Heim, C., Newport, D. J., Wagner, D., Wilcox, M. M., Miller, A. H., & Nemeroff, C. B. (2002). The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: A multiple regression analysis. Depression and Anxiety, 15, 117125. doi:10.1002/da.10015
Heim, C., Plotsky, P. M., & Nemeroff, C. B. (2004). Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology, 29, 641648. doi:10.1038/sj.npp.1300397
Herbison, C. E., Henley, D., Marsh, J., Atkinson, H., Newnham, J. P., Matthews, S. G., … Pennell, C. E. (2016). Characterization and novel analyses of acute stress response patterns in a population-based cohort of young adults: Influence of gender, smoking, and BMI. Stress, 19, 139150. doi:10.3109/10253890.2016.1146672
Jones, B. L., Nagin, D. S., & Roeder, K. (2001). A SAS procedure based on mixture models for estimating developmental trajectories. Sociological Methods and Research, 29, 374393.
Juster, R. P., Bizik, G., Picard, M., Arsenault-Lapierre, G., Sindi, S., Trepanier, L., … Lupien, S. J. (2011). A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development. Development and Psychopathology, 23, 725776. doi:10.1017/S0954579411000289
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry, 156, 837841.
Kessler, R. C. (1997). The effects of stressful life events on depression. Annual Review of Psychology, 48, 191214.
Kofman, O. (2002). The role of prenatal stress in the etiology of developmental behavioural disorders. Neuroscience and Biobehavioral Review, 26, 457470.
Konstantakou, P., Mastorakos, G., Vrachnis, N., Tomlinson, J. W., & Valsamakis, G. (2017). Dysregulation of 11beta-hydroxysteroid dehydrogenases: Implications during pregnancy and beyond. Journal of Maternal-Fetal Neonatal Medicine, 30, 284293. doi:10.3109/14767058.2016.1171308
Kudielka, B. M., & Kirschbaum, C. (2005). Sex differences in HPA axis responses to stress: A review. Biolological Psychology, 69, 113132.
Laceulle, O. M., O'Donnell, K., Glover, V., O'Connor, T. G., Ormel, J., van Aken, M. A., & Nederhof, E. (2014). Stressful events and psychological difficulties: Testing alternative candidates for sensitivity. European Child and Adolescent Psychiatry, 23, 103113. doi:10.1007/s00787-013-0436-4
Levine, S. Z., Levav, I., Yoffe, R., & Pugachova, I. (2014). The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia. Schizophrenia Research, 158, 236240. doi:10.1016/j.schres.2014.07.003
Li, J., Olsen, J., Vestergaard, M., & Obel, C. (2010). Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: A nationwide follow-up study in Denmark. European Child and Adolescent Psychiatry, 19, 747753. doi:10.1007/s00787-010-0113-9
Liu, R. T. (2015). A developmentally informed perspective on the relation between stress and psychopathology: When the problem with stress is that there is not enough. Journal of Abnormal Psychology, 124, 8092. doi:10.1037/abn0000043
Lovibond, S. H., & Lovibond, P. F. (1995). Manual for the Depression Anxiety Stress Scales (2nd ed.). Sydney, Australia: Psychology Foundation.
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10, 434445.
Mazure, C. M. (1998). Life stressors as risk factors in depression. Clinical Psychology: Science and Practice, 5, 291313. doi:10.1111/j.1468-2850.1998.tb00151.x
McCormick, C. M., & Mathews, I. Z. (2010). Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34, 756765. doi:10.1016/j.pnpbp.2009.09.019
Meaney, M. J., Szyf, M., & Seckl, J. R. (2007). Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends in Molecular Medicine, 13, 269277. doi:10.1016/j.molmed.2007.05.003
Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin, 133, 2545.
Mueller, B. R., & Bale, T. L. (2008). Sex-specific programming of offspring emotionality after stress early in pregnancy. Journal of Neuroscience, 28, 90559065. doi:10.1523/jneurosci.1424-08.2008
Nagin, D. S., & Odgers, C. L. (2010). Group-based trajectory modeling in clinical research. Annuual Review of Clinical Psychology, 6, 109138.
Nemeroff, C. B., Heim, C. M., Thase, M. E., Klein, D. N., Rush, A. J., Schatzberg, A. F., … Keller, M. B. (2003). Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proceedings of the National Academy of Sciences, 100, 1429314296. doi:10.1073/pnas.2336126100
Newnham, J. P., Evans, S. F., Michael, C. A., Stanley, F. J., & Landau, L. I. (1993). Effects of frequent ultrasound during pregnancy: A randomised controlled trial. Lancet, 342, 887891.
O'Connor, T. G., Heron, J., Golding, J., Glover, V., & ALSPAC Study Team. (2003). Maternal antenatal anxiety and behavioural/emotional problems in children: A test of a programming hypothesis. Journal of Child Psychology and Psychiatry, 44, 10251036.
Osman, A., Wong, J. L., Bagge, C. L., Freedenthal, S., Gutierrez, P. M., & Lozano, G. (2012). The Depression Anxiety Stress Scales-21 (DASS-21): Further examination of dimensions, scale reliability, and correlates. Journal of Clinical Psychology, 68, 13221338. doi:10.1002/jclp.21908
Pena, C. J., Monk, C., & Champagne, F. A. (2012). Epigenetic effects of prenatal stress on 11B-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLOS ONE, 7, e39791. doi:doi:10.1371/journal.pone.0039791
Robinson, M., Mattes, E., Oddy, W. H., Pennell, C. E., Van Eekelen, A., McLean, N. J., … Newnhan, J. P. (2011). Prenatal stress and risk of behavioral morbidity from age 2 to 14 years: The influence of the number, type and timing of stressful life events. Development and Psychopathology, 23, 507520.
Robinson, M., Oddy, W. H., McLean, N. J., Jacoby, P., Pennell, C. E., de Klerk, N. H., … Newnham, J. P. (2010). Low-moderate prenatal alcohol exposure and risk to child behavioural development: A prospective cohort study. British Journal of Gynaecology, 117, 11391150. doi:10.1111/j.1471-0528.2010.02596.x
Rodriguez, A., & Bohlin, G. (2005). Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? Journal of Child Psychology and Psychiatry, 46, 246254. doi:10.1111/j.1469-7610.2004.00359.x
Romeo, R. D. (2010a). Adolescence: A central event in shaping stress reactivity. Development and Psychobiology, 52, 244253. doi:10.1002/dev.20437
Romeo, R. D. (2010b). Pubertal maturation and programming of hypothalamic-pituitary-adrenal reactivity. Frontiers in Neuroendocrinology, 31, 232240. doi:10.1016/j.yfrne.2010.02.004
Sapolsky, R. M. (2015). Stress and the brain: Individual variability and the inverted-U. Nature Neuroscience, 18, 13441346. doi:10.1038/nn.4109
Schilling, E. A., Aseltine, R. H., & Gore, S. (2008). The impact of cumulative childhood adversity on young adult mental health: Measures, models, and interpretations. Social Science and Medicine, 66, 11401151.
Seery, M. D., Leo, R. J., Lupien, S. P., Kondrak, C. L., & Almonte, J. L. (2013). An upside to adversity? Moderate cumulative lifetime adversity is associated with resilient responses in the face of controlled stressors. Psychological Science, 24, 11811189. doi:10.1177/0956797612469210
Seo, D., Tsou, K. A., Ansell, E. B., Potenza, M. N., & Sinha, R. (2014). Cumulative adversity sensitizes neural response to acute stress: Association with health symptoms. Neuropsychopharmacology, 39, 670680. doi:10.1038/npp.2013.250
Sukantarat, K. T., Williamson, R. C., & Brett, S. J. (2007). Psychological assessment of ICU survivors: A comparison between the Hospital Anxiety and Depression Scale and the Depression, Anxiety and Stress Scale. Anaesthesia, 62, 239243. doi:10.1111/j.1365-2044.2006.04948.x
Talge, N. M., Neal, C., Glover, V., & Early Stress, Translational Research and Prevention Science Network. (2007). Antenatal maternal stress and long-term effects on child neurodevelopment: How and why? Journal of Child Psychology and Psychiatry, 48, 245261. doi:10.1111/j.1469-7610.2006.01714.x
Tearne, J. E., Allen, K. L., Herbison, C. E., Lawrence, D., Whitehouse, A. J., Sawyer, M. G., & Robinson, M. (2015). The association between prenatal environment and children's mental health trajectories from 2 to 14 years. European Child and Adolescent Psychiatry, 24, 10151024. doi:10.1007/s00787-014-0651-7
Tennant, C., & Andrews, G. (1976). A scale to measure the stress of life events. Australian and New Zealand Journal of Psychiatry, 10, 2732.
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012). Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: Preliminary findings in healthy adults. PLOS ONE, 7, e30148. doi:10.1371/journal.pone.0030148
Van den Bergh, B. R., Mulder, E. J., Mennes, M., & Glover, V. (2005). Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms. A review. Neuroscience & Biobehavioral Reviews, 29, 237258. doi:10.1016/j.neubiorev.2004.10.007
Van den Bergh, B. R., Van Calster, B., Smits, T., Van Huffel, S., & Lagae, L. (2008). Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: A prospective study on the fetal origins of depressed mood. Neuropsychopharmacology, 33, 536545. doi:10.1038/sj.npp.1301450
Vedhara, K., Metcalfe, C., Brant, H., Crown, A., Northstone, K., Dawe, K., … Smith, G. D. (2012). Maternal mood and neuroendocrine programming: Effects of time of exposure and sex. Journal of Neuroendocrinology, 24, 9991011. doi:10.1111/j.1365-2826.2012.02309.x
Vinkers, C. H., Joels, M., Milaneschi, Y., Kahn, R. S., Penninx, B. W., & Boks, M. P. (2014). Stress exposure across the life span cumulatively increases depression risk and is moderated by neuroticism. Depression and Anxiety, 31, 737745. doi:10.1002/da.22262
Weinstock, M. (2001). Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Progress in Neurobiology, 65, 427451.
Type Description Title
Supplementary materials

Herbison supplementary material
Figure S1

 Word (145 KB)
145 KB

The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure

  • Carly E. Herbison (a1), Karina Allen (a1) (a2) (a3), Monique Robinson (a1), John Newnham (a1) and Craig Pennell (a1)...


Altmetric attention score

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