Changes in cortical thickness across the lifespan in major depressive disorder Wanda Truong a , Luciano Minuzzi b,c , Claudio N. Soares b,c , Benicio N. Frey b,c , Alan C. Evans d , Glenda M. MacQueen e , Geoffrey B.C. Hall f,n a McMaster Integrative Neuroscience Discovery and Study Program (MiNDS), McMaster University, Hamilton, ON, Canada L8S 4K1 b Mood Disorders Program, St. Joseph's Healthcare, Hamilton, ON, Canada L8S 4K1 c Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, ON, Canada L8S 4K1 d McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 0G4 e Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada T2N 1N4 f Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada L8S 4K1 article info Article history: Received 21 December 2012 Received in revised form 3 September 2013 Accepted 8 September 2013 Keywords: Mood disorders Brain structure Age-of-onset Neurodevelopment Magnetic resonance imaging abstract Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on age-of-onset. Our aim was to compare patients who differ in age-of-onset, while controlling for illness duration, and number of depressive episodes. By directly comparing early-(EOD) and late-onset (LOD) patients, we examined whether age-of-onset is associated with changes in the extent or spatial pattern of cortical thickness. Cross-sectional comparison of cortical thickness in EOD vs. LOD. Age-of-onset was determined based on self-report, with EOD defined as onset prior to age 25. Reduced cortical thickness in the dorsal–lateral prefrontal cortex (DLPFC), pre- and postcentral gyrus, and the lingual gyrus were found in EOD compared to healthy controls (p o0.001). In linear regression models controlling for number of episodes, illness duration, severity, and sex, differences (at p o0.001) were found between EOD and LOD in the bilateral posterior cingulate, parahippocampal gyri, right precuneus, lingual, and fusiform gyri, but not the DLPFC. EOD is associated with greater disturbances in cortical thickness than LOD, even when duration of illness and other factors are controlled. These results provide novel insights on how development of depression is differentiated by age. & 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on the age of first onset (e.g. MacMaster and Kusumakar, 2004). Early- (EOD) and late-onset depression (LOD) may differ in their genetic origins, symptomatology, course, and prognosis (Zisook et al., 2004; Gollan et al., 2005; Korten et al., 2012). EOD is associated with more suicide attempts, sadness, irritability, neuroticism, childhood-onset anxiety disorders, and atypical symptoms, com- pared to LOD (Zisook et al., 2004; Korten et al., 2012). Several studies have indicated that patients with EOD have poor out- comes, including poor response to antidepressant treatment, greater illness severity, higher relapse rate (Heim et al., 2004; Dekker et al., 2007; Kemp et al., 2008), and greater duration of illness, after adjusting for current age (Zisook et al., 2004). A consistent finding in the literature that separates the clinical profile of EOD from LOD is a greater prevalence of family history in EOD patients (Kendler et al., 2001; Weissman et al., 2004; Williamson et al., 2004; Peterson et al., 2009). A longitudinal study (Weissman et al., 2004), spanning three generations found an effect of familial loading. Furthermore, there seems to be a trend toward decreasing age-of-onset with each successive birth cohort, with more recent generations experiencing depression at a progressively younger age (Lavori et al., 1993). Specifically, an epidemiological study found that patients with a first-onset of depression before the age of 25 were more likely to have a family history of depression than LOD patients (Kendler et al., 2001). Relatively little attention has been focused on neurobiological differences between patients with EOD and LOD. One study of cortical gyrification in bipolar disorder (BD) shows that patterns of cortical folding can differentiate between early-(before age 25 years), intermediate-(age 25–45 years), and late-onset (after age 45) patients (Penttila et al., 2009). This work demonstrates that mood disorders can have a differential impact on the brain depending on the neurodevelopmental stage at which an illness has its first onset. Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/psychresns Psychiatry Research: Neuroimaging 0925-4927/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pscychresns.2013.09.003 n Corresponding author. Tel.: þ1 905 525 9140x23033; fax: þ1 905 529 6225. E-mail address: hallg@mcmaster.ca (G.B.C. Hall). Psychiatry Research: Neuroimaging 214 (2013) 204–211