Hippocampal volumes in schizophrenic twins

CONTEXT The effects of genes and environment on brain abnormalities in schizophrenia remain unclear. OBJECTIVE To examine the contributions of genes and environment to hippocampal volume reduction in schizophrenia. DESIGN Population-based twin cohort study. SETTING Finland. PARTICIPANTS Seven monozygotic (MZ) twin pairs concordant for schizophrenia and 16 MZ and 32 dizygotic (DZ) twin pairs discordant for schizophrenia, ascertained so as to be representative of all such probands in a Finnish birth cohort, along with 28 MZ and 26 DZ healthy comparison twin pairs without a family history of psychosis. MAIN OUTCOME MEASURES Hippocampal volume measurements taken from high-resolution magnetic resonance images. RESULTS Hippocampal volumes of probands were smaller than those of their nonschizophrenic MZ and DZ co-twins and healthy twins. Hippocampal volumes of probands' non-ill co-twins were smaller than those of healthy twins, but those of non-ill MZ and DZ co-twins of schizophrenic patients were similar. The intraclass correlations for hippocampal volumes among healthy and discordant MZ pairs were larger than those among the respective DZ pairs. The intraclass correlation for healthy MZ pairs was larger than that for discordant MZ pairs, and the variance component estimate for additive genetic effects was lower in discordant twins than in healthy twins. CONCLUSIONS Although hippocampal volume in healthy individuals is largely affected by genetic factors, it is subject to substantially greater modulation by environmental factors in schizophrenic patients and their relatives. The results are discussed in view of assumptions underlying classic twin methods.

[1]  E. Torrey,et al.  Schizophrenia And Manic-depressive Disorder: The Biological Roots Of Mental Illness As Revealed By The Landmark Study Of Identical Twins , 1994 .

[2]  S. Resnick,et al.  An image-processing system for qualitative and quantitative volumetric analysis of brain images. , 1998, Journal of computer assisted tomography.

[3]  Eve C Johnstone,et al.  Magnetic resonance imaging of brain in people at high risk of developing schizophrenia , 1999, The Lancet.

[4]  Dorret I Boomsma,et al.  Twin-singleton differences in brain structure using structural equation modelling. , 2002, Brain : a journal of neurology.

[5]  D. Weinberger,et al.  ANATOMICAL ABNORMALITIES IN THE BRAINS OF MONOZYGOTIC TWINS DISCORDANT AND CONCORDANT FOR SCHIZOPHRENIA , 1992, Clinical neuropharmacology.

[6]  H. Whalley,et al.  Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings , 2002, Journal of neurology, neurosurgery, and psychiatry.

[7]  G. Vogler,et al.  Methodology for genetic studies of twins and families , 1993 .

[8]  Tyrone D. Cannon,et al.  Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors. , 1993, Archives of general psychiatry.

[9]  E. Walker,et al.  Plasma hormones and catecholamine metabolites in monozygotic twins discordant for psychosis. , 2002, Neuropsychiatry, neuropsychology, and behavioral neurology.

[10]  Shiva M. Singh,et al.  Epigenetic contributors to the discordance of monozygotic twins , 2002, Clinical genetics.

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

[12]  Theo G. M. van Erp,et al.  A Twin Study of Genetic Contributions to Hippocampal Morphology in Schizophrenia , 2002, Neurobiology of Disease.

[13]  Jacob Cohen A Coefficient of Agreement for Nominal Scales , 1960 .

[14]  Sophia Frangou,et al.  Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications , 1999, Biological Psychiatry.

[15]  L. DeLisi,et al.  Perinatal complications and reduced size of brain limbic structures in familial schizophrenia. , 1988, Schizophrenia bulletin.

[16]  B. Knowlton,et al.  Remembering episodes: a selective role for the hippocampus during retrieval , 2000, Nature Neuroscience.

[17]  A Pfefferbaum,et al.  Heritability of hippocampal size in elderly twin men: Equivalent influence from genes and environment , 2001, Hippocampus.

[18]  Tyrone D. Cannon,et al.  The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. , 2000, American journal of human genetics.

[19]  Nikos Makris,et al.  Thalamic and amygdala–hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis , 1999, Biological Psychiatry.

[20]  T. Kent,et al.  New genetic hypothesis of schizophrenia. , 1999, Medical hypotheses.

[21]  Karen F. Berman,et al.  Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia , 1994, Psychiatry Research: Neuroimaging.

[22]  W. Hoeffding,et al.  Contributions to Probability and Statistics: Essays in Honor of Harold Hotelling. , 1962 .

[23]  V S Caviness,et al.  Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study. , 1997, American journal of medical genetics.

[24]  Michael D. Nelson,et al.  Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging : A meta-analytic study , 1998 .

[25]  J. Kennedy,et al.  Unstable genes--unstable mind? , 1995, The American journal of psychiatry.

[26]  D. Posthuma,et al.  Twin–singleton differences in intelligence? , 2000, Twin Research.

[27]  T. Goldberg,et al.  Learning and memory in monozygotic twins discordant for schizophrenia , 1993, Psychological Medicine.

[28]  D. Weinberger,et al.  Relationship of obstetric complications and differences in size of brain structures in monozygotic twin pairs discordant for schizophrenia. , 2000, The American journal of psychiatry.

[29]  Tyrone D. Cannon On the nature and mechanisms of obstetric influences in schizophrenia: a review and synthesis of epidemiologic studies , 1997 .

[30]  Tyrone D. Cannon,et al.  The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. , 1998, Archives of general psychiatry.

[31]  D. M. Lyons,et al.  Early life stress and inherited variation in monkey hippocampal volumes. , 2001, Archives of general psychiatry.

[32]  N. Niikawa,et al.  Genomic discordance between monozygotic twins discordant for schizophrenia. , 1998, The American journal of psychiatry.

[33]  DNA stability and schizophrenia in twins , 2003 .

[34]  Nikos Makris,et al.  Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. , 2002, Archives of general psychiatry.

[35]  Oili Salonen,et al.  Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder, their unaffected siblings, and healthy unrelated volunteers. , 2002, The American journal of psychiatry.

[36]  Abraham Weizman,et al.  Evidence for the involvement of the hippocampus in the pathophysiology of schizophrenia , 2000, European Neuropsychopharmacology.

[37]  Nancy C. Andreasen,et al.  Problems with ratio and proportion measures of imaged cerebral structures , 1991, Psychiatry Research: Neuroimaging.

[38]  S. Shapiro,et al.  An Analysis of Variance Test for Normality (Complete Samples) , 1965 .

[39]  J. Kaprio,et al.  Population-based twin registries: illustrative applications in genetic epidemiology and behavioral genetics from the Finnish Twin Cohort Study. , 1990, Acta geneticae medicae et gemellologiae.

[40]  R. Murray,et al.  OBSTETRIC COMPLICATIONS AND AGE AT ONSET IN SCHIZOPHRENIA : AN INTERNATIONAL COLLABORATIVE META-ANALYSIS OF INDIVIDUAL PATIENT DATA , 1998 .

[41]  Niels G. Waller The Scale for the Assessment of Negative Symptoms , 1995 .

[42]  H. Pétursson,et al.  No evidence of expansion of CAG or GAA repeats in schizophrenia families and monozygotic twins , 1998, Human Genetics.

[43]  J. Born,et al.  Brain morphology in adolescents at genetic risk for schizophrenia assessed by qualitative and quantitative magnetic resonance imaging 1 1 This letter was received on 15 June 1998 and accepted for publication on 29 January 1999. , 1999, Schizophrenia Research.

[44]  E. Cantor-Graae,et al.  Obstetric complications in histories of monozygotic twins discordant and concordant for schizophrenia , 1994, Acta psychiatrica Scandinavica.

[45]  J. Pierri,et al.  Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: Preliminary studies , 1997, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

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

[47]  J. Ragland,et al.  Neuropsychological assessment of monozygotic twins discordant for schizophrenia. , 1990, Archives of general psychiatry.