Twin-singleton differences in brain structure using structural equation modelling.

Twin studies are important to investigate genetic influences on variation in human brain morphology in health and disease. However, the twin method has been criticized for its alleged non-generalizability due to differences in the intrauterine and family environment of twins, compared with singletons. To test whether twin-singleton differences complicate interpretation of genetic contributions on variation in brain volume, brains from 112 pairs of twins and 34 of their siblings with a mean (standard deviation) age of 30.7 (9.6) years were scanned using MRI. The influence of birth order, zygosity and twin-sibling differences on brain volume measures was analysed using maximum-likelihood model fitting. Variances were homogeneous across birth order, zygosity and twin-singleton status. Irrespective of zygosity, intracranial volume was smaller in second-born twins compared with first-born twins and compared with siblings. Grey matter volume was smaller in second-born twins compared with first-born twins. White matter was smaller in twins compared with siblings. Differences in grey and white matter between these groups were no longer significant after correction for intracranial volume. Total brain, and lateral and third ventricle volumes were comparable in twins and singletons. In conclusion, second-born twins have a smaller intracranial volume than their first-born co-twins and siblings. This suggests aberrant early brain development in second-born twins, which is consistent with the suboptimal pre- and perinatal environment related to birth order in twins. Since other brain volume measures were comparable between the groups, twin studies can provide reliable estimates of heritabilities in brain volume measures and these can be generalized to the singleton population.

[1]  B. Price.  Primary biases in twin studies; a review of prenatal and natal difference-producing factors in monozygotic pairs. , 1950, American journal of human genetics.

[2]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[3]  Adolf Pfefferbaum,et al.  Brain structure in men remains highly heritable in the seventh and eighth decades of life☆ , 2000, Neurobiology of Aging.

[4]  R. S. Kahn,et al.  Prenatal exposure to famine and brain morphology in schizophrenia , 2000, Schizophrenia Research.

[5]  E. J. van den Oord,et al.  A genetic study of maternal and paternal ratings of problem behaviors in 3-year-old twins. , 1996, Journal of Abnormal Psychology.

[6]  R. Murray,et al.  Imaging as a tool in exploring the neurodevelopment and genetics of schizophrenia. , 1996, British medical bulletin.

[7]  D. Boomsma,et al.  Etiology of individual differences in birth weight of twins as a function of maternal smoking during pregnancy. , 1998, Twin research : the official journal of the International Society for Twin Studies.

[8]  Dorret I. Boomsma,et al.  A Note on the Statistical Power in Extended Twin Designs , 2000, Behavior genetics.

[9]  A. Reveley,et al.  CEREBRAL VENTRICULAR SIZE IN TWINS DISCORDANT FOR SCHIZOPHRENIA , 1982, The Lancet.

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

[11]  S. G. Vandenberg.  Does a special twin situation contribute to similarity for abilities in MZ and DZ twins? , 1984, Acta geneticae medicae et gemellologiae.

[12]  R. Kahn,et al.  Multivariate Genetic Analysis of Brain Structure in an Extended Twin Design , 2000, Behavior genetics.

[13]  R. Wilson,et al.  Twin growth: initial deficit, recovery, and trends in concordance from birth to nine years. , 1979, Annals of human biology.

[14]  D. Weinberger,et al.  Genetic variability of human brain size and cortical gyral patterns. , 1997, Brain : a journal of neurology.

[15]  F. Müller,et al.  Human embryology & teratology , 1996 .

[16]  J. Lessing,et al.  Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies. , 2000, Fertility and sterility.

[17]  R. Guttman,et al.  Similarities in test scores and profiles of kibbutz twins and singletons. , 1984, Acta geneticae medicae et gemellologiae.

[18]  D. Boomsma,et al.  Twin registers in Europe: an overview , 1998, Twin Research.

[19]  R. Kahn,et al.  Quantitative genetic modeling of variation in human brain morphology. , 2001, Cerebral cortex.

[20]  T. Mckeown,et al.  An investigation of the difference in measured intelligence between twins and single births * , 1970, Annals of human genetics.

[21]  R. Kahn,et al.  Automated Separation of Gray and White Matter from MR Images of the Human Brain , 2001, NeuroImage.

[22]  R. S. Kahn,et al.  Automatic Segmentation of the Ventricular System from MR Images of the Human Brain , 2001, NeuroImage.

[23]  N. Martin,et al.  Self-report psychiatric symptoms in twins and their nontwin relatives: are twins different? , 1995, American journal of medical genetics.

[24]  B Anderson,et al.  Brain size, head size, and intelligence quotient in monozygotic twins. , 1999, Neurology.

[25]  B L Miller,et al.  Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. , 1998, Stroke.

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

[27]  D. V. von Cramon,et al.  Sulcal variability of twins. , 1999, Cerebral cortex.

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

[29]  M. Fowler,et al.  Double jeopardy: twin infant mortality in the United States, 1983 and 1984. , 1991, American journal of obstetrics and gynecology.

[30]  Alan C. Evans,et al.  Statistical Sulcal Shape Comparisons: Application to the Detection of Genetic Encoding of the Central Sulcus Shape , 2000, NeuroImage.

[31]  David N. Kennedy,et al.  A Twin MRI Study of Size Variations in the Human Brain , 2000, Journal of Cognitive Neuroscience.

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

[33]  R. Paul,et al.  Twin Gestations: I. Antenatal Care and Complications , 1989, Obstetrics and gynecology.

[34]  M. Allin,et al.  Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term. , 2001, Brain : a journal of neurology.

[35]  P. F. Tolstikhin.  [The outcome of multiple pregnancy]. , 1962, Voprosy okhrany materinstva i detstva.

[36]  J. Nurnberger,et al.  Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. , 1994, Archives of general psychiatry.

[37]  D. Hay,et al.  The La Trobe Twin Study: a genetic approach to the structure and development of cognition in twin children. , 1983, Child development.

[38]  Guy Marchal,et al.  Multimodality image registration by maximization of mutual information , 1997, IEEE Transactions on Medical Imaging.

[39]  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.

[40]  A. Hockley,et al.  Intracranial volume change in craniosynostosis. , 1999, Journal of neurosurgery.

[41]  Guy Marchal,et al.  Multi-modality image registration by maximization of mutual information , 1996, Proceedings of the Workshop on Mathematical Methods in Biomedical Image Analysis.