Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuropsychobiology 2008;58:128–137 DOI: 10.1159/000182889 Cognitive Performance and Grey Matter Density in Psychosis: Functional Relevance of a Structural Endophenotype P. Habets a L. Krabbendam a P. Hofman b J. Suckling c F. Oderwald a E. Bullmore e P. Woodruff d J. Van Os a, f M. Marcelis a a Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, b Department of Radiology, University Hospital Maastricht, Maastricht, The Netherlands; c Brain Mapping Unit, Department of Psychiatry, University of Cambridge and Addenbrooke’s Hospital, Cambridge, d Department of Psychiatry, Sheffield Cognition and Neuroimaging Laboratory, Academic Clinical Psychiatry, University of Sheffield, Longley Centre, Sheffield, e Department of Psychiatry, University of Cambridge, Cambridge, and f Division of Psychological Medicine, Institute of Psychiatry, London, UK patients and relatives, strategic retrieval from semantic memory was positively associated with grey matter density in basal ganglia structures. Some additional negative asso- ciations in the patients differentiated this group from rela- tives. Conclusions: The overlap in structure-function rela- tionships in individuals with schizophrenia and those with liability for the disorder may suggest that regional grey matter density alterations functionally alter particular neu- rocircuits, which could lead to cognitive deficits. The non- overlapping structure-function correlations may reflect dis- ease-related or compensatory mechanisms. Copyright © 2008 S. Karger AG, Basel Introduction Cortical and subcortical brain alterations as well as compromised cognitive performance have been consis- tently identified as disease and liability markers for schizophrenia [1–4] , with greater effect sizes for the for- mer than the latter. Various relative and twin studies on schizophrenia have shown that grey matter deficits in frontal and temporal cortices as well as in the thalamus Key Words Psychosis  Magnetic resonance imaging  Grey matter  Cognition  Family study  Endophenotype Abstract Background: Structural brain changes and cognitive impair- ments have been identified as indicators of genetic risk for schizophrenia. However, the pattern of associations be- tween such structural and functional liability markers has been less well investigated. Methods: Magnetic resonance imaging data and cognitive assessments were acquired in 31 patients with psychosis, 32 non-psychotic first-degree rela- tives and 28 controls. The relationship between cerebral grey matter density and cognitive performance was exam- ined using computational morphometry. Results: Two out of 6 cognitive tests revealed significant associations with grey matter density in regions of the frontal lobe, basal gan- glia, thalamus and cerebellum in patients and relatives. In patients, poorer executive functioning was associated with cerebellar grey matter density deficits. In relatives, poorer executive functioning was associated with increased grey matter density in the cerebellum and frontal lobe. In both Received: December 7, 2007 Accepted after revision: September 5, 2008 Published online: December 16, 2008 Dr. Machteld Marcelis Department of Psychiatry and Neuropsychology PO Box 616 (VIJV1), 6200 MD Maastricht (The Netherlands) Tel. +31 43 368 8679, Fax +31 43 368 8689 E-Mail m.marcelis@sp.unimaas.nl © 2008 S. Karger AG, Basel 0302–282X/08/0584–0128$24.50/0 Accessible online at: www.karger.com/nps Downloaded by: Universiteit Maastricht 137.120.157.72 - 10/24/2013 10:26:53 AM