Ventricular enlargement in schizophrenia is associated with a genetic polymorphism at the interleukin-1 receptor antagonist gene

Magnetic resonance imaging (MRI) studies have shown some morphological and volumetric peculiarities in brains of schizophrenic patients. The authors explored the influence of genetic polymorphisms at interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genes on these abnormalities. Hippocampus, lateral ventricles, and dorsolateral prefrontal cortex gray matter volumes were measured in a sample of 23 DSM-IV diagnosed schizophrenic patients of Spanish origin using MRI scans; MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n = 45). IL-1B and IL-1RN genes, involved in neurodevelopment and neurodegenerative processes, were analyzed in the patient sample. Patients carrying VNTR-allele*2 of IL-1RN gene showed a significant enlargement of both left (P = 0.002) and right (P = 0.01) ventricles. Sex and illness duration were controlled for in the analyses. Our results, though preliminary, suggest that IL-1RN gene might contribute to the ventricular volumetric changes observed in schizophrenic patients.

[1]  A. Korten,et al.  Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. , 1992, Psychological medicine. Monograph supplement.

[2]  J. Ashburner,et al.  Multimodal Image Coregistration and Partitioning—A Unified Framework , 1997, NeuroImage.

[3]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[4]  A. Zhablenski Schizophrenia : manifestations, incidence and course in different cultures , 1992 .

[5]  N C Andreasen,et al.  Heritability of BDNF alleles and their effect on brain morphology in schizophrenia. , 1999, American journal of medical genetics.

[6]  Daniel A. Lim,et al.  Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain , 1999, Cell.

[7]  Sergi Papiol,et al.  Interleukin‐1β (IL‐1β) gene and increased risk for the depressive symptom‐dimension in schizophrenia spectrum disorders , 2004 .

[8]  Vincent Magnotta,et al.  Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. , 2003, Archives of general psychiatry.

[9]  T Sigmundsson,et al.  Brain changes in schizophrenia , 1998, British Journal of Psychiatry.

[10]  Andrés Santos,et al.  Multimodality image quantification using the Talairach grid , 2001, SPIE Medical Imaging.

[11]  Sergi Papiol,et al.  Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom-dimension in schizophrenia spectrum disorders. , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[12]  M S Buchsbaum,et al.  Ventricular enlargement associated with linkage marker for schizophrenia-related disorders in one pedigree. , 1996, Molecular psychiatry.

[13]  M. Buchsbaum,et al.  Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. , 2004, The American journal of psychiatry.

[14]  R. Murray,et al.  Meta-analysis of regional brain volumes in schizophrenia. , 2000, The American journal of psychiatry.

[15]  D. Weinberger,et al.  Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. , 1990, The New England journal of medicine.

[16]  P. McKenna,et al.  Schizophrenia – a Brain Disease? a Critical Review of Structural and Functional Cerebral Abnormality in the Disorder , 1995, British Journal of Psychiatry.

[17]  R. Kahn,et al.  Volumes of brain structures in twins discordant for schizophrenia. , 2001, Archives of general psychiatry.

[18]  R. McCarley,et al.  A review of MRI findings in schizophrenia , 2001, Schizophrenia Research.

[19]  N C Andreasen,et al.  Tumor necrosis factor receptor-II: heritability and effect on brain morphology in schizophrenia , 2000, Molecular Psychiatry.

[20]  M. Egan,et al.  Neurobiology of schizophrenia. , 1993, Current opinion in neurology and neurosurgery.

[21]  A. Reveley,et al.  The genetic basis of cerebral ventricular volume , 1984, Psychiatry Research.

[22]  K O Lim,et al.  Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. , 1992, Alcoholism, clinical and experimental research.

[23]  N C Andreasen,et al.  Reversibility of brain tissue loss in anorexia nervosa assessed with a computerized Talairach 3-D proportional grid , 1996, Psychological Medicine.

[24]  Allan L. Reiss,et al.  Automated Talairach atlas-based parcellation and measurement of cerebral lobes in children , 1999, Psychiatry Research: Neuroimaging.

[25]  J W Kim,et al.  Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder , 2004, Psychiatric genetics.

[26]  N. Rothwell,et al.  Cytokines and acute neurodegeneration , 1997, Molecular Psychiatry.

[27]  R. Murray,et al.  Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. , 1999, Archives of general psychiatry.

[28]  Nicolette Marshall,et al.  A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia , 2004, Biological Psychiatry.

[29]  John H Gilmore,et al.  Prenatal Infection and Risk for Schizophrenia: IL-1β, IL-6, and TNFα Inhibit Cortical Neuron Dendrite Development , 2004, Neuropsychopharmacology.

[30]  B. Gutiérrez,et al.  Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder , 2004, Journal of Medical Genetics.

[31]  N C Andreasen,et al.  Automatic atlas-based volume estimation of human brain regions from MR images. , 1996, Journal of computer assisted tomography.

[32]  R S Kahn,et al.  Structural brain abnormalities in patients with schizophrenia and their healthy siblings. , 2000, The American journal of psychiatry.

[33]  John H Gilmore,et al.  Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development. , 2004, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[34]  H Nawa,et al.  Cytokine and growth factor involvement in schizophrenia—support for the developmental model , 2000, Molecular Psychiatry.

[36]  D. Rujescu,et al.  Methionine Homozygosity at Codon 129 in the Prion Protein Is Associated with White Matter Reduction and Enlargement of CSF Compartments in Healthy Volunteers and Schizophrenic Patients , 2002, NeuroImage.

[37]  Hiroshi Kunugi,et al.  Dinucleotide repeat polymorphism in the neurotrophin-3 gene and hippocampal volume in psychoses , 1999, Schizophrenia Research.

[38]  U Hegerl,et al.  Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia. , 2001, The American journal of psychiatry.

[39]  M. Hurme,et al.  Polymorphisms of the interleukin-1 gene complex in schizophrenia , 1999, Molecular Psychiatry.

[40]  Douglas W. Jones,et al.  Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.