Cerebral cortical thickness and a history of obstetric complications in schizophrenia Unn Kristin Haukvik a, * , Glenn Lawyer a , Petr Szulc Bjerkan a , Cecilie Bhandari Hartberg a , Erik G. Jönsson b , Thomas McNeil c , Ingrid Agartz a,b,d a Institute of Psychiatry, University of Oslo, P.O. Box 85 Vinderen, N-0319 Oslo, Norway b Department of Clinical Neuroscience, HUBIN Project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden c Department of Psychiatric Epidemiology, Lund University Hospital USiL, SE-221 85 Lund, Sweden d Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, N-0319 Oslo, Norway article info Article history: Received 5 November 2008 Received in revised form 24 April 2009 Accepted 5 May 2009 Keywords: Schizophrenia Obstetric complications Cortical thickness MRI Neurodevelopment Hypoxia abstract Introduction: Magnetic resonance imaging (MRI) studies have demonstrated that patients with schizo- phrenia have thinner brain cortices compared with healthy control subjects. Neurodevelopment is vul- nerable to obstetric complications (OCs) such as hypoxia and birth trauma, factors that are also related to increased risk of developing schizophrenia. With the hypothesis that OCs might explain the thinner cortices found in schizophrenia, we studied patients with schizophrenia and healthy controls subjects for association between number and severity of OCs and variation in cortical thickness. Methods: MRI scans of 54 adults with schizophrenia or schizoaffective disorder and 54 healthy controls were acquired at Karolinska Institutet, Stockholm, Sweden. Measures of brain cortical thickness were obtained using automated computer processing (FreeSurfer). OCs were assessed from obstetric records and scored blindly according to the McNeil–Sjöström scale. At numerous cortical locations, putative effects of OCs on cortical thickness variation were tested for each trimester, for labour, for composite OC scores, severe OC scores, and hypoxia scores among patients and controls separately. Results: Number and severity of OCs varied among both patient and control subjects but were not asso- ciated with cortical thickness in either of the groups. Patients demonstrated thinner brain cortices but there were no significant differences in number and severity of OC scores across groups. Conclusion: In the present study, number and severity of obstetric complications were not associated with brain cortical thickness, in patients with schizophrenia or in healthy control subjects. The thinner brain cortices found in patients with schizophrenia were not explained by a history of OCs. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction 1.1. Obstetric complications in schizophrenia A growing body of evidence indicates that a detrimental prena- tal environment and obstetric complications (OCs) are related to increased risk of schizophrenia (Byrne et al., 2007; Cannon et al., 2002a; Dalman et al., 2001; Geddes et al., 1999; Hultman et al., 1999). The occurrence of OCs may disturb the early brain develop- ment, and thereby increase the risk of later development of the ill- ness (Marenco and Weinberger, 2000; Rapoport et al., 2005; Weinberger, 1987). Several adverse pre- and perinatal factors have demonstrated statistical association with an increased risk of schizophrenia; some of which are being subjected to maternal starvation (Hoek et al., 1998) or infection (Brown et al., 2004) dur- ing foetal life, late winter birth (Hultman et al., 1999), birth as- phyxia (Dalman et al., 2001), or being born small for gestational age (Jones et al., 1998). These factors have been suggested to inter- fere with normal brain development through effects of pro-inflam- matory cytokines such as Tumor Necrosis Factor alpha and Interleukin-6 in maternal starvation (Shen et al., 2008) and infec- tion (Smith et al., 2007), or more generally through foetal hypoxia (Verdoux and Sutter, 2002). In the present study, OCs were defined as ‘‘...the broad class of somatic deviations from an expected, nor- mal course of events and offspring development during pregnancy, labour-delivery, and the early neonatal period” (McNeil, 1988). 1.2. Structural MRI-findings in schizophrenia A large number of magnetic resonance imaging (MRI) studies have demonstrated brain morphological alterations such as larger lateral ventricles, smaller hippocampal volumes (Honea et al., 2005; Shenton et al., 2001 for review) and thinner brain cortices (Kuperberg et al., 2003; Nesvåg et al., 2008; Voets et al., 2008) in patients with schizophrenia compared to healthy subjects. The neuropathology underlying the cortical thinning reported in schizophrenia is poorly understood (DeLisi et al., 2006; Harrison, 0022-3956/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2009.05.001 * Corresponding author. Tel.: +47 22029839; fax: +47 22495861. E-mail address: unn.haukvik@medisin.uio.no (U.K. Haukvik). Journal of Psychiatric Research 43 (2009) 1287–1293 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires