Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: A cross-sectional comparison Emma Sprooten a,b,c,1 , Martina Papmeyer a, ⁎ ,1 , Annya M. Smyth a , Daniel Vincenz a,d , Sibylle Honold a,d , Guy A. Conlon a,e , T. William J. Moorhead a , Dominic Job a , Heather C. Whalley a , Jeremy Hall a , Andrew M. McIntosh a , David C.G. Owens a , Eve C. Johnstone a , Stephen M. Lawrie a a Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom b Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA c Olin Neuropsychiatry Center, Institute of Living, Hartford Hospital, Hartford, CT, USA d Faculty of Electrical Engineering and Information Technology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany e University of Edinburgh Medical School, Edinburgh, United Kingdom abstract article info Article history: Received 15 April 2013 Received in revised form 13 September 2013 Accepted 27 September 2013 Available online 10 October 2013 Keywords: Schizophrenia Psychosis High-risk First-episode Grey matter Cortical thickness Background: Schizophrenia is associated with cortical thickness reductions in the brain, but it is unclear whether these are present before illness onset, and to what extent they are driven by genetic factors. Methods: In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at high familial risk for schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were acquired, and clinical information was collected for the following 10 years for the high-risk and control group. During this time, 17 high-risk individuals developed schizophrenia, on average 2.5 years after the scan, and 57 experienced isolated or sub-clinical psychotic symptoms. We applied surface-based analysis of the cerebral cortex to this cohort, and extracted cortical thickness in automatically parcellated regions. Results: Analysis of variance revealed widespread thinning of the cerebral cortex in first-episode patients, most pronounced in superior frontal, medial parietal, and lateral occipital regions (corrected p b 10 -4 ). In contrast, cor- tical thickness reductions were only found in high-risk individuals in the left middle temporal gyrus (corrected p b 0.05). There were no significant differences between those at high risk who later developed schizophrenia and those who remained well. Conclusions: These findings confirm cortical thickness reductions in schizophrenia patients. Increased familial risk for schizophrenia is associated with thinning in the left middle temporal lobe, irrespective of subsequent dis- ease onset. The absence of widespread cortical thinning before disease onset implies that the cortical thinning is unlikely to simply reflect genetic liability to schizophrenia but is predominantly driven by disease-associated factors. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Schizophrenia is associated with reduced grey matter in the brain, as repeatedly shown by magnetic resonance imaging (MRI) studies (Lawrie and Abukmeil, 1998; Shenton et al., 2001; Ellison- Wright et al., 2008; Glahn et al., 2008), but the pathogenesis of these deficits remains unclear. Since schizophrenia is highly heritable (Sullivan et al., 2003), a prevailing question is to what extent they are driven by genetic factors. It is also unclear to what extent they are present before illness onset, as opposed to secondary to the illness or long-term medication use. Studying unaffected relatives and patients at early stages of the illness can help to disentangle the relationships between brain structure, symptoms and neuro-developmental disruptions in the ab- sence of illness-related confounds. Meta-analyses of volumetric and voxel-based morphometry studies show that grey matter volume reductions in schizophrenia are found most consistently in the insula, superior temporal and medial prefrontal regions, and around the thalamus, while reductions in parietal, occipital and superior frontal regions have been less well replicated (Lawrie and Abukmeil, 1998; Shenton et al., 2001; Honea et al., 2005; Ellison-Wright et al., 2008; Glahn et al., 2008; Fornito et al., 2009; Bora et al., 2011; Chan et al., 2011). Studies investigating cortical thickness, however, have ob- served more widespread thinning across both hemispheres of the cere- bral cortex, particularly not only in the frontal and temporal lobes but also to some extent in parietal and occipital regions (Kuperberg et al., 2003; Rimol et al., 2010). In unaffected individuals at increased familial risk from the Edinburgh High Risk Study (EHRS), we previously found subtle grey matter density Schizophrenia Research 151 (2013) 259–264 ⁎ Corresponding author at: University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, United Kingdom. Tel.: +44 131 5376187; fax: +44 131 537 6531. E-mail address: Martina.Papmeyer@ed.ac.uk (M. Papmeyer). 1 ES and MP contributed equally to this work. 0920-9964/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2013.09.024 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres