Early development, stress and depression across the life course: pathways to depression in a national British birth cohort I. Colman 1 *, P. B. Jones 2 , D. Kuh 3 , M. Weeks 1 , K. Naicker 1 , M. Richards 3 and T. J. Croudace 4 1 Department of Epidemiology and Community Medicine, University of Ottawa, ON, Canada 2 Department of Psychiatry, University of Cambridge, UK 3 MRC Unit for Lifelong Health and Ageing, Institute of Epidemiology and Health Care, University College London, UK 4 Department of Health Sciences, University of York, UK Background. The aetiology of depression is multifactorial, with biological, cognitive and environmental factors across the life course influencing risk of a depressive episode. There is inconsistent evidence linking early life development and later depression. The aim of this study was to investigate relationships between low birthweight (LBW), infant neurodevelopment, and acute and chronic stress as components in pathways to depression in adulthood. Method. The sample included 4627 members of the National Survey of Health and Development (NSHD; the 1946 British birth cohort). Weight at birth, age of developmental milestones, economic deprivation in early childhood, acute stressors in childhood and adulthood, and socio-economic status (SES) in adulthood were assessed for their direct and indirect effects on adolescent (ages 13 and 15 years) and adult (ages 36, 43 and 53 years) measures of depressive symptoms in a structural equation modelling (SEM) framework. A structural equation model developed to incorporate all variables exhibited excellent model fit according to several indices. Results. The path of prediction from birthweight to age of developmental milestones to adolescent depression/anxiety to adult depression/anxiety was significant (p< 0.001). Notably, direct paths from birthweight (p = 0.25) and age of develop- mental milestones ( p =0.23) to adult depression were not significant. Childhood deprivation and stressors had important direct and indirect effects on depression. Stressors in adulthood were strongly associated with adult depression. Conclusions. Depression in adulthood is influenced by an accumulation of stressors across the life course, including many that originate in the first years of life. Effects of early-life development on mental health appear by adolescence. Received 6 August 2013; Revised 30 January 2014; Accepted 1 February 2014; First published online 27 February 2014 Key words: Depression, development, life course, stress. Introduction The aetiology of depression is thought to be multifac- torial, with genetic, biological, cognitive and environ- mental factors interacting across the life course to influence the risk of a depressive episode among indi- viduals of varying disposition. Historically, epidemio- logical research on depression has tended to focus on individual risk factors. However, to best understand the development of depression, such research must embrace the complex nature among various pathways to risk (Colman & Jones, 2004; Colman & Ataullahjan, 2010). Seminal work by Kendler et al. (2002, 2006) used twin registry data to study the development of depression in men and women, using structural equation modelling (SEM) of key determinants and their association over time. Eighteen key risk factors were considered, and the results indicated three key pathways that lead to an episode of major depression, with different periods of influence for each dimension: (1) internalizing behaviour and liability that manifests itself early in life, (2) externalizing behaviour from ado- lescence to adulthood, and (3) variation in adversity across the life course (Kendler et al. 2002, 2006). Prenatal and infant development may be important in determining risk for depression later in life. Low birthweight (LBW) has been linked to depression in adolescence (Gale & Martyn, 2004; Costello et al. 2007; Colman et al. 2012) and adulthood (Thompson et al. 2001; Gale & Martyn, 2004; Hack et al. 2004; Alati et al. 2007; Colman et al. 2007a). This supports a fetal programming hypothesis in which prenatal stress at crucial periods of fetal brain development may elicit a maladaptive hyper-responsiveness to stress that could persist well into the life course (Weinstock, 2007). * Address for correspondence: Dr I. Colman, Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Room 3230C, Ottawa, ON, Canada K1H 8M5. (Email: icolman@uottawa.ca) Psychological Medicine (2014), 44, 2845–2854. © Cambridge University Press 2014 doi:10.1017/S0033291714000385 ORIGINAL ARTICLE http://dx.doi.org/10.1017/S0033291714000385 Downloaded from http:/www.cambridge.org/core. Auraria Library, on 25 Oct 2016 at 01:38:39, subject to the Cambridge Core terms of use, available at http:/www.cambridge.org/core/terms.