BRIEF REPORTSEvidence for association between structural variants in lissencephaly-related genes and executive deficits in schizophrenia or bipolar patients from a Spanish isolate populationTabarés-Seisdedos, Rafaela b; Mata, Ignaciof; Escámez, Teresab c; Vieta, Eduardb d; López-Ilundain, Jose M.e; Salazar, Josea b; Selva, Gabriela b; Balanzá, Vicentea b; Rubio, Cristinaa b; Martínez-Arán, Anabelb d; Valdés-Sánchez, Lourdesc; Geijo-Barrientos, Emiliod; Martínez, SalvadordAuthor Information aTeaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Valencia bCIBER-SAM, Ciber en Salud Mental, Instituto de Salud Carlos III, Madrid cExperimental Embryology Laboratory, Institute of Neuroscience CSIC-UMH, Campus de San Juan, San Juan de Alicante, Alicante dBipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic, IDIBAPS, Barcelona, Stanley Medical Research Institute Center, University of Barcelona, Barcelona eFundación Argibide, Pamplona, Navarra, Spain fDepartment of Psychiatry, University Hospital Marques de Valdecilla, Santander, Spain Correspondence to Dr Ignacio Mata, MD, PhD, Department of Psychiatry, University Hospital Marques de Valdecilla, Avda. Marques de Valdecilla s/n, 39008-Santander, Cantabria, Spain Tel: +34 942202973; e-mail: [email protected] Received 10 July 2007 Revised 18 April 2008 Accepted 11 June 2008 Psychiatric Genetics: December 2008 - Volume 18 - Issue 6 - p 313-317 doi: 10.1097/YPG.0b013e3283118725 Buy Metrics Abstract There is evidence for an association between structural variants in genes for lissencephaly, which are involved in neuronal migration, and prefrontal cognitive deficits in schizophrenia and bipolar patients. On the basis of these intriguing findings, we analyzed 16 markers located in the lissencephaly critical region (LCR in chromosome 17p13.3) in 124 schizophrenic, 56 bipolar, and 141 healthy individuals. All recruits were from a Spanish population isolate of Basque origin that is characterized by low genetic heterogeneity. In addition, we examined whether structural genomic variations in the LCR were associated with executive cognition. Twenty-three patients (12.8%), but none of the controls, showed structural variants (deletions and insertions) in either of two markers related with lissencephaly (D17S1566 on tumor suppressor gene TP53: tumor protein p53 and D17S22 on SMG6 gene: Smg-6 homolog, nonsense mediated mRNA decay factor– Caenorhabditis elegans). These patients performed significantly worse in the Wisconsin Card Sorting Test-Categories in comparison with patients without such variations in lissencephaly-related genes. The presence of structural variants was related to completed categories, and accounted for 10.7% of the variance (P=0.001). Finally, logistic regression showed that poor Wisconsin Card Sorting Test-Categories performance was the only predictor of belonging to the positive LCR variations group. These new findings provide further evidence for the association between some lissencephaly-related genes and both schizophrenia and bipolar disorder, and influence on frontal executive functioning. © 2008 Lippincott Williams & Wilkins, Inc.