Human Brain Volume: What’s in the Genes#

  • Jiska S. Peper
  • Marcel P. Zwiers
  • Dorret I. Boomsma
  • Reneacute S. Kahn
  • Hilleke E. Hulshoff Pol

The human brain continues to grow considerably after birth. Compared to measurements taken at birth (mean, SD was 34.9, 1.1 cm), head circumference was found to increase by more than 30% in the first year (46.6, 1.3 cm); between 1 and 4 years of age it increased by another 9% (50.9, 1.4 cm) and between 4 and 8 years by an additional 4% (53.4, 1.4 cm) in a normal cohort (Gale, O’Callaghan, Bredow,&Martyn, 2006). Magnetic resonance imaging (MRI) research has shown that at 6 years of age total cerebral volume has reached 95% of its adult volume (Giedd et al., 1999). However, the brain continues to show dynamic changes from childhood into adulthood in overall gray and white matter and in subcortical structures. In early adolescence gray matter starts to decrease (Giedd et al., 1999), whereas overall white matter volume still increases (Bartzokis et al., 2001; Giedd et al., 1999; Paus et al., 1999). Also, subcortical structures show developmental changes after childhood. For instance, the thalamus and caudate nucleus decrease with age (Sowell, Trauner, Gamst,&Jernigan, 2002) and the posterior hippocampus increases with age, whereas the anterior hippocampus decreases with age (Gogtay et al., 2006) (for a review on brain maturation, see Toga, Thompson,&Sowell, 2006).


White Matter Down Syndrome Diffusion Tensor Imaging Brain Volume Twin Pair 
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  1. Atwood, L. D., Wolf, P. A., Heard-Costa, N. L., Massaro, J. M., Beiser, A., D’Agostino, R. B., et al. (2004). Genetic variation in white matter hyperintensity volume in the Framingham Study. Stroke, 35, 1609–1613.PubMedGoogle Scholar
  2. Aylward, E. H., Brandt, J., Codori, A. M., Mangus, R. S., Barta, P. E., & Harris, G. J. (1994). Reduced basal ganglia volume associated with the gene for Huntington’s disease in asymptomatic at-risk persons. Neurology, 44, 823–828.PubMedGoogle Scholar
  3. Aylward, E. H., Li, Q., Stine, O. C., Ranen, N., Sherr, M., Barta, P. E., et al. (1997). Longitudinal change in basal ganglia volume in patients with Huntington’s disease. Neurology, 48, 394–399.PubMedGoogle Scholar
  4. Aylward, E. H., Anderson, N. B., Bylsma, F. W., Wagster, M. V., Barta, P. E., Sherr, M., et al. (1998). Frontal lobe volume in patients with Huntington’s disease. Neurology, 50, 252–258.PubMedGoogle Scholar
  5. Aylward, E. H., Li, Q., Honeycutt, N. A., Warren, A. C., Pulsifer, M. B., Barta, P. E., et al. (1999). MRI volumes of the hippocampus and amygdala in adults with Down’s syndrome with and without dementia. American Journal of Psychiatry, 156, 564–568.PubMedGoogle Scholar
  6. Aylward, E. H., Codori, A. M., Rosenblatt, A., Sherr, M., Brandt, J., Stine, O. C., et al. (2000). Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington’s disease. Movement Disorders, 15, 552–560.PubMedGoogle Scholar
  7. Aylward, E. H., Sparks, B. F., Field, K. M., Yallapragada, V., Shpritz, B. D., Rosenblatt, A., et al. (2004). Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology, 63, 66–72.PubMedGoogle Scholar
  8. Baarè, W. F., Hulshoff Pol, H. E., Boomsma, D. I., Posthuma, D., de Geus, E. J., Schnack, H. G., et al. (2001). Quantitative genetic modeling of variation in human brain morphology. Cerebral Cortex, 11, 816–824.Google Scholar
  9. Barnea-Goraly, N., Menon, V., Krasnow, B., Ko, A., Reiss, A., & Eliez, S. (2003). Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study. American Journal of Psychiatry, 160, 1863–1869.PubMedGoogle Scholar
  10. Bartley, A. J., Jones, D. W., & Weinberger, D. R. (1997). Genetic variability of human brain size and cortical gyral patterns. Brain, 120(Pt 2), 257–269.PubMedGoogle Scholar
  11. Bartzokis, G., Beckson, M., Lu, P. H., Nuechterlein, K. H., Edwards, N., & Mintz, J. (2001). Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Archives of General Psychiatry, 58, 461–465.PubMedGoogle Scholar
  12. Bassett, A. S., Chow, E. W.C., AbdelMalik, P., Gheorghiu, M., Husted, J., & Weksberg, R. (2003). The schizophrenia phenotype in 22q11 deletion syndrome. American Journal of Psychiatry, 160, 1580–1586.PubMedGoogle Scholar
  13. Beglinger, L. J., Nopoulos, P. C., Jorge, R. E., Langbehn, D. R., Mikos, A. E., Moser, D. J., et al. (2005). White matter volume and cognitive dysfunction in early Huntington’s disease. Cognitive and Behavioral Neurology, 18, 102–107.PubMedGoogle Scholar
  14. Bish, J. P., Nguyen, V., Ding, L., Ferrante, S., & Simon, T. J. (2004). Thalamic reductions in children with chromosome 22q11.2 deletion syndrome. Neuroreport, 15, 1413–1415.PubMedGoogle Scholar
  15. Bish, J. P., Pendyal, A., Ding, L., Ferrante, H., Nguyen, V., Donald-McGinn, D., et al. (2006). Specific cerebellar reductions in children with chromosome 22q11.2 deletion syndrome. Neuroscience Letters, 399, 245–248.PubMedGoogle Scholar
  16. Boddaert, N., Mochel, F., Meresse, I., Seidenwurm, D., Cachia, A., Brunelle, F., et al. (2006). Parieto-occipital grey matter abnormalities in children with Williams syndrome. Neuroimage, 30, 721–725.PubMedGoogle Scholar
  17. Bond, J., Roberts, E., Mochida, G. H., Hampshire, D. J., Scott, S., Askham, J. M., et al. (2002). ASPM is a major determinant of cerebral cortical size. Nature Genetics, 32, 316–320.PubMedGoogle Scholar
  18. Bonelli, R. M., Wenning, G. K., & Kapfhammer, H. P. (2004). Huntington’s disease: present treatments and future therapeutic modalities. International Clinical Psychopharmacology, 19, 51–62.PubMedGoogle Scholar
  19. Boomsma, D., Busjahn, A., & Peltonen, L. (2002). Classical twin studies and beyond. Nature Reviews Genetics, 3, 872–882.PubMedGoogle Scholar
  20. Bremner, J. D., & Vermetten E. (2004). Neuroanatomical changes associated with pharmacotherapy in posttraumatic stress disorder. Biobehavioral Stress Response: Protective and Damaging Effects, 1032, 154–157.Google Scholar
  21. Bueller, J. A., Aftab, M., Sen, S., Gomez-Hassan, D., Burmeister, M., & Zubieta, J. K. (2006). BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biological Psychiatry, 59, 812–815.PubMedGoogle Scholar
  22. Cairo, S., Merla, G., Urbinati, F., Ballabio, A., & Reymond A. (2001). WBSCR14, a gene mapping to the Williams–Beuren syndrome deleted region, is a new member of the Mlx transcription factor network. Human Molecular Genetics, 10, 617–627.PubMedGoogle Scholar
  23. Callicott, J. H., Straub, R. E., Pezawas, L., Egan, M. F., Mattay, V. S., Hariri, A. R., et al. (2005). Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 102, 8627–8632.PubMedGoogle Scholar
  24. Campbell, L. E., Daly, E., Toal, F., Stevens, A., Azuma, R., Catani, M., et al. (2006). Brain and behaviour in children with 22q11.2 deletion syndrome: A volumetric and voxel-based morphometry MRI study. Brain, 129, 1218–1228.PubMedGoogle Scholar
  25. Cannon, T. D., Hennah, W., van Erp, T. G., Thompson, P. M., Lonnqvist, J., Huttunen, M., et al. (2005). Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry, 62, 1205–1213.PubMedGoogle Scholar
  26. Carmelli, D., DeCarli, C., Swan, G. E., Jack, L. M., Reed, T., Wolf, P. A., et al. (1998). Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke, 29, 1177–1181.PubMedGoogle Scholar
  27. Carmelli, D., Reed, T., & DeCarli C. (2002). A bivariate genetic analysis of cerebral white matter hyperintensities and cognitive performance in elderly male twins. Neurobiology of Aging, 23, 413–420.PubMedGoogle Scholar
  28. Cherniske, E. M., Carpenter, T. O., Klaiman, C., Young, E., Bregman, J., Insogna, K., et al. (2004). Multisystem study of 20 older adults with Williams syndrome. American Journal of Medical Genetics, 131A, 255–264.Google Scholar
  29. Cohen, R. M., Small, C., Lalonde, F., Friz, J., & Sunderland T. (2001). Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women. Neurology, 57, 2223–2228.PubMedGoogle Scholar
  30. Danoff, S. K., Taylor, H. E., Blackshaw, S., & Desiderio S. (2004). TFII-I, a candidate gene for Williams syndrome cognitive profile: Parallels between regional expression in mouse brain and human phenotype. Neuroscience, 123, 931–938.PubMedGoogle Scholar
  31. de Leeuw, F. E., Richard, F., de Groot, J. C., van Duijn, C. M., Hofman, A., van Gijn, J., et al. (2004). Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke, 35, 1057–1060.PubMedGoogle Scholar
  32. DeCarli, C., Miller, B. L., Swan, G. E., Reed, T., Wolf, P. A., & Carmelli D. (2001). Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Archives of Neurology, 58, 643–647.PubMedGoogle Scholar
  33. DeCarli, C., Massaro, J., Harvey, D., Hald, J., Tullberg, M., Au, R., et al. (2005). Measures of brain morphology and infarction in the Framingham heart study: establishing what is normal. Neurobiology of Aging, 26, 491–510.PubMedGoogle Scholar
  34. DeStefano, A. L., Atwood, L. D., Massaro, J. M., Heard-Costa, N., Beiser, A., Au, R., et al. (2006). Genome-wide scan for white matter hyperintensity: The Framingham Heart Study. Stroke, 37, 77–81.PubMedGoogle Scholar
  35. Durston, S., Fossella, J. A., Casey, B. J., Hulshoff Pol, H. E., Galvan, A., Schnack, H. G., et al. (2005). Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls. Molecular Psychiatry, 10, 678–685.PubMedGoogle Scholar
  36. Eckert, M. A., Leonard, C. M., Molloy, E. A., Blumenthal, J., Zijdenbos, A., & Giedd, J. N. (2002). The epigenesis of planum temporale asymmetry in twins. Cerebral Cortex, 12, 749–755.PubMedGoogle Scholar
  37. Eckert, M. A., Hu, D., Eliez, S., Bellugi, U., Galaburda, A., Korenberg, J., et al. (2005). Evidence for superior parietal impairment in Williams syndrome. Neurology, 64, 152–153.PubMedGoogle Scholar
  38. Eliez, S., Schmitt, J. E., White, C. D., & Reiss, A. L. (2000). Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. American Journal of Psychiatry, 157, 409–415.PubMedGoogle Scholar
  39. Eliez, S., Blasey, C. M., Schmitt, E. J., White, C. D., Hu, D., & Reiss, A. L. (2001). Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia? American Journal of Psychiatry, 158, 447–453.PubMedGoogle Scholar
  40. Eliez, S., Schmitt, J. E., White, C. D., Wellis, V. G., & Reiss, A. L. (2001). A quantitative MRI study of posterior fossa development in velocardiofacial syndrome. Biological Psychiatry, 49, 540–546.PubMedGoogle Scholar
  41. Evans, P. D., Anderson, J. R., Vallender, E. J., Gilbert, S. L., Malcom, C. M., Dorus, S., et al. (2004). Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human Molecular Genetics, 13, 489–494.PubMedGoogle Scholar
  42. Fennema-Notestine, C., Archibald, S. L., Jacobson, M. W., Corey-Bloom, J., Paulsen, J. S., Peavy, G. M., et al. (2004). In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease. Neurology, 63, 989–995.PubMedGoogle Scholar
  43. Ferland, R. J., Cherry, T. J., Preware, P. O., Morrisey, E. E., & Walsh, C. A. (2003). Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. Journal of Comparative Neurology, 460, 266–279.PubMedGoogle Scholar
  44. Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P., & Pembrey, M. E. (1998). Localisation of a gene implicated in a severe speech and language disorder. Nature Genetics, 18, 168–170.PubMedGoogle Scholar
  45. Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestart, M. L., et al. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America, 102, 10604–10609.PubMedGoogle Scholar
  46. Frangou, S., Aylward, E., Warren, A., Sharma, T., Barta, P., & Pearlson G. (1997). Small planum temporale volume in Down’s syndrome: a volumetric MRI study. American Journal of Psychiatry, 154, 1424–1429.PubMedGoogle Scholar
  47. Gale, C.R., O’Callaghan, F. J., Bredow, M., & Martyn, C. N. (2006). The influence of head growth in fetal life, infancy, and childhood on intelligence at the ages of 4 and 8 years. Pediatrics, 118, 1486–1492.PubMedGoogle Scholar
  48. Geschwind, D. H., Miller, B. L., DeCarli, C., & Carmelli D. (2002). Heritability of lobar brain volumes in twins supports genetic models of cerebral laterality and handedness. Proceedings of the National Academy of Sciences of the United States of America, 99, 3176–3181.PubMedGoogle Scholar
  49. Giedd, J. N., Blumenthal, J., Jeffries, N. O., Castellanos, F. X., Liu, H., Zijdenbos, A., Paus, T., et al. (1999). Brain development during childhood and adolescence: A longitudinal MRI study. Nature Neuroscience, 2, 861–863.PubMedGoogle Scholar
  50. Gogtay, N., Nugent, T. F., III, Herman, D. H., Ordonez, A., Greenstein, D., Hayashi, K. M., et al. (2006). Dynamic mapping of normal human hippocampal development. Hippocampus, 16, 664–672.PubMedGoogle Scholar
  51. Gothelf, D., Eliez, S., Thompson, T., Hinard, C., Penniman, L., Feinstein, C., et al. (2005). COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nature Neuroscience, 8, 1500–1502.PubMedGoogle Scholar
  52. Harris, G. J., Pearlson, G. D., Peyser, C. E., Aylward, E. H., Roberts, J., Barta, P. E., et al. (1992). Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington’s disease. Annals of Neurology, 31, 69–75.PubMedGoogle Scholar
  53. Ho, A. K., Sahakian, B. J., Brown, R. G., Barker, R. A., Hodges, J. R., Ane, M. N., et al. (2003). Profile of cognitive progression in early Huntington’s disease. Neurology, 61, 1702–1706.PubMedGoogle Scholar
  54. Hoogenraad, C. C., Eussen, B. H., Langeveld, A., van Haperen, R., Winterberg, S., Wouters, C. H., et al. (1998). The murine CYLN2 gene: genomic organization, chromosome localization, and comparison to the human gene that is located within the 7q11.23 Williams syndrome critical region. Genomics, 53, 348–358.PubMedGoogle Scholar
  55. Hoogenraad, C. C., Koekkoek, B., Akhmanova, A., Krugers, H., Dortland, B., Miedema, M., et al. (2002). Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nature Genetics, 32, 116–127.PubMedGoogle Scholar
  56. Hulshoff Pol, H. E., Posthuma, D., Baare, W. F., de Geus, E. J., Schnack, H. G., van Haren, N. E., et al. (2002). Twin-singleton differences in brain structure using structural equation modelling. Brain, 125, 384–390.PubMedGoogle Scholar
  57. Hulshoff Pol, H. E., Schnack, H. G., Posthuma, D., Mandl, R. C.W., Baare, W. F., van Oel, C., et al. (2006). Genetic contributions to human brain morphology and intelligence. Journal of Neuroscience, 40, 10235–10242.Google Scholar
  58. Jernigan, T. L., & Bellugi U. (1990). Anomalous brain morphology on magnetic resonance images in Williams syndrome and Down syndrome. Archives of Neurology, 47, 529–533.PubMedGoogle Scholar
  59. Jernigan, T. L., Salmon, D. P., Butters, N., & Hesselink, J. R. (1991). Cerebral structure on MRI, Part II: Specific changes in Alzheimer’s and Huntington’s diseases. Biological Psychiatry, 29, 68–81.PubMedGoogle Scholar
  60. Jernigan, T. L., Bellugi, U., Sowell, E., Doherty, S., & Hesselink, J. R. (1993). Cerebral morphologic distinctions between Williams and Down syndromes. Archives of Neurology, 50, 186–191.PubMedGoogle Scholar
  61. Jones, W., Hesselink, J., Courchesne, E., Duncan, T., Matsuda, K., & Bellugi U. (2002). Cerebellar abnormalities in infants and toddlers with Williams syndrome. Developmental Medicine and Child Neurology, 44, 688–694.PubMedGoogle Scholar
  62. Kassubek, J., Bernhard, L. G., Ecker, D., Juengling, F. D., Muche, R., Schuller, S., et al. (2004). Global cerebral atrophy in early stages of Huntington’s disease: Quantitative MRI study. Neuroreport, 15, 363–365.PubMedGoogle Scholar
  63. Kassubek, J., Juengling, F. D., Kioschies, T., Henkel, K., Karitzky, J., Kramer, B., et al. (2004). Topography of cerebral atrophy in early Huntington’s disease: A voxel based morphometric MRI study. Journal of Neurology Neurosurgery and Psychiatry, 75, 213–220.Google Scholar
  64. Kassubek, J., Juengling, F. D., Ecker, D., & Landwehrmeyer, G. B. (2005). Thalamic atrophy in Huntington’s disease co-varies with cognitive performance: A morphometric MRI analysis. Cerebral Cortex, 15, 846–853.PubMedGoogle Scholar
  65. Kates, W. R., Burnette, C. P., Jabs, E. W., Rutberg, J., Murphy, A. M., Grados, M., et al. (2001). Regional cortical white matter reductions in velocardiofacial syndrome: A volumetric MRI analysis. Biological Psychiatry, 49, 677–684.PubMedGoogle Scholar
  66. Kates, W. R., Burnette, C. P., Bessette, B. A., Folley, B. S., Strunge, L., Jabs, E. W., et al. (2004). Frontal and caudate alterations in velocardiofacial syndrome (deletion at chromosome 22q11.2). Journal of Child Neurology, 19, 337–342.PubMedGoogle Scholar
  67. Kates, W. R., Antshel, K. M., Abdulsabur, N., Colgan, D., Funke, B., Fremont, W., et al. (2006). A gender-moderated effect of a functional COMT polymorphism on prefrontal brain morphology and function in velo-cardio-facial syndrome (22q11.2 deletion syndrome). American Journal of Medical Genetics part B: Neuropsychiatric Genetics, 141, 274–280.Google Scholar
  68. Kates, W. R., Miller, A. M., Abdulsabur, N., Antshel, K. M., Conchelos, J., Fremont, W., et al. (2006). Temporal lobe anatomy and psychiatric symptoms in velocardiofacial syndrome (22q11.2 deletion syndrome). Journal of the American Academy of Child and Adolescent Psychiatry, 45, 587–595.PubMedGoogle Scholar
  69. Kesslak, J. P., Nagata, S. F., Lott, I., & Nalcioglu O. (1994). Magnetic resonance imaging analysis of age-related changes in the brains of individuals with Down’s syndrome. Neurology, 44, 1039–1045.PubMedGoogle Scholar
  70. Kippenhan, J. S., Olsen, R. K., Mervis, C. B., Morris, C. A., Kohn, P., Lindenberg, A. M., et al. (2005). Genetic contributions to human gyrification: Sulcal morphometry in Williams syndrome. Journal of Neuroscience, 25, 7840–7846.PubMedGoogle Scholar
  71. Kipps, C. M., Duggins, A. J., Mahant, N., Gomes, L., Ashburner, J., & McCusker, E. A. (2005). Progression of structural neuropathology in preclinical Huntington’s disease: A tensor based morphometry study. Journal of Neurology Neurosurgery and Psychiatry, 76, 650–655.Google Scholar
  72. Krasuski, J. S., Alexander, G. E., Horwitz, B., Rapoport, S. I., & Schapiro, M. B. (2002). Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down’s syndrome: Implications for the prodromal phase of Alzheimer’s disease. American Journal of Psychiatry, 159, 74–81.PubMedGoogle Scholar
  73. Kurotaki, N., Imaizumi, K., Harada, N., Masuno, M., Kondoh, T., Nagai, T., et al. (2002). Haploinsufficiency of NSD1 causes Sotos syndrome. Nature Genetics, 30, 365–366.PubMedGoogle Scholar
  74. Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F., & Monaco, A. P. (2001). A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, 413, 519–523.PubMedGoogle Scholar
  75. Lai, C. S., Gerrelli, D., Monaco, A. P., Fisher, S. E., & Copp, A. J. (2003). FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder. Brain, 126, 2455–2462.PubMedGoogle Scholar
  76. Lemaitre, H., Crivello, F., Dufouil, C., Grassiot, B., Tzourio, C., Alperovitch, A., et al. (2005). No epsilon4 gene dose effect on hippocampal atrophy in a large MRI database of healthy elderly subjects. Neuroimage, 24, 1205–1213.PubMedGoogle Scholar
  77. Levitin, D. J., Menon, V., Schmitt, J. E., Eliez, S., White, C. D., Glover, G. H., et al. (2003). Neural correlates of auditory perception in Williams syndrome: An fMRI study. Neuroimage, 18, 74–82.PubMedGoogle Scholar
  78. Lieberman, J. A., Tollefson, G. D., Charles, C., Zipursky, R., Sharma, T., Kahn, R. S., et al. (2005). Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry, 62, 361–370.PubMedGoogle Scholar
  79. Lind, J., Larsson, A., Persson, J., Ingvar, M., Nilsson, L. G., Backman, L., et al. (2006). Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory. Neuroscience Letters, 396, 23–27.PubMedGoogle Scholar
  80. Lott, I. T., & Head E. (2001). Down syndrome and Alzheimer’s disease: A link between development and aging. Mental Retardation and Developmental Disabilities Research Reviews, 7, 172–178.PubMedGoogle Scholar
  81. Martin, N. G., Boomsma, D. I., & Machin, G. (1997). A twin-pronged attack on complex traits. Nature Genetics, 17, 387–392.PubMedGoogle Scholar
  82. Mascalchi, M., Lolli, F., Della, N. R., Tessa, C., Petralli, R., Gavazzi, C., et al. (2004). Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain. Radiology, 232, 867–873.PubMedGoogle Scholar
  83. Mekel-Bobrov, N., Gilbert, S. L., Evans, P. D., Vallender, E. J., Anderson, J. R., Hudson, R. R., et al. (2005). Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science, 309, 1720–1722.PubMedGoogle Scholar
  84. Meng, Y., Zhang, Y., Tregoubov, V., Janus, C., Cruz, L., Jackson, M., et al. (2002). Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron, 35, 121–133.PubMedGoogle Scholar
  85. Meyer-Lindenberg, A., Kohn, P., Mervis, C. B., Kippenhan, J. S., Olsen, R. K., Morris, C. A., et al. (2004). Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron, 43, 623–631.PubMedGoogle Scholar
  86. Meyer-Lindenberg, A., Buckholtz, J. W., Kolachana, B., Hariri, R., Pezawas, L., Blasi, G., et al. (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences of the United States of America, 103, 6269–6274.PubMedGoogle Scholar
  87. Morris, C. A., Mervis, C. B., Hobart, H. H., Gregg, R. G., Bertrand, J., Ensing, G. J., et al. (2003). GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region. American Journal of Medical Genetics A, 123, 45–59.Google Scholar
  88. Murphy, K. C., Jones, L. A., & Owen, M. J. (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry, 56, 940–945.PubMedGoogle Scholar
  89. Nemoto, K., Ohnishi, T., Mori, T., Moriguchi, Y., Hashimoto, R., Asada, T., et al. (2006). The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology. Neuroscience Letters, 397, 25–29.PubMedGoogle Scholar
  90. Nokelainen, P. & Flint, J. (2002). Genetic effects on human cognition: lessons from the study of mental retardation syndromes. Journal of Neurology Neurosurgery and Psychiatry, 72, 287–296.Google Scholar
  91. Paulsen, J. S., Magnotta, V. A., Mikos, A. E., Paulson, H. L., Penziner, E., Andreasen, N. C., et al. (2006). Brain structure in preclinical Huntington’s disease. Biological Psychiatry, 59, 57–63.PubMedGoogle Scholar
  92. Paus, T., Zijdenbos, A., Worsley, K., Collins, D. L., Blumenthal, J., Giedd, J. N., et al. (1999). Structural maturation of neural pathways in children and adolescents: in vivo study. Science, 283, 1908–1911.PubMedGoogle Scholar
  93. Pearlson, G. D., Breiter, S. N., Aylward, E. H., Warren, A. C., Grygorcewicz, M., Frangou, S., et al. (1998). MRI brain changes in subjects with Down syndrome with and without dementia. Developmental Medicine and Child Neurology, 40, 326–334.PubMedGoogle Scholar
  94. Peinemann, A., Schuller, S., Pohl, C., Jahn, T., Weindl, A., & Kassubek J. (2005). Executive dysfunction in early stages of Huntington’s disease is associated with striatal and insular atrophy: a neuropsychological and voxel-based morphometric study. Journal of the Neurological Sciences, 239, 11–19.PubMedGoogle Scholar
  95. Pennington, B. F., Filipek, P. A., Lefly, D., Chhabildas, N., Kennedy, D. N., Simon, J. H., et al. (2000). A twin MRI study of size variations in human brain. Journal of Cognitive Neuroscience, 12, 223–232.PubMedGoogle Scholar
  96. Peper, J. S., Zwiers, M. P., van Leeuwen, M., Van den Berg, S. M., Boomsma, D. I., Kahn, R. S., et al. (2004). Genetic modeling of cognitive brain maturation in pre-adolescence: A longitudinal study in twins. Twin Research and Human Genetics, 7, S172.Google Scholar
  97. Pezawas, L., Verchinski, B. A., Mattay, V. S., Callicott, J. H., Kolachana, B. S., Straub, R. E., et al. (2004). The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. Journal of Neuroscience, 24, 10099–10102.PubMedGoogle Scholar
  98. Pfefferbaum, A., Sullivan, E. V., Swan, G. E., & Carmelli D. (2000). Brain structure in men remains highly heritable in the seventh and eighth decades of life. Neurobiology of Aging, 21, 63–74.PubMedGoogle Scholar
  99. Pfefferbaum, A., Sullivan, E. V., & Carmelli D. (2004). Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability. Neurobiology of Aging, 25, 175–183.PubMedGoogle Scholar
  100. Pinter, J. D., Brown, W. E., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001). Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study. Neurology, 56, 972–974.PubMedGoogle Scholar
  101. Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001). Neuroanatomy of Down’s syndrome: a high-resolution MRI study. American Journal of Psychiatry, 158, 1659–1665.PubMedGoogle Scholar
  102. Posthuma, D. & Boomsma, D. I. (2000). A note on the statistical power in extended twin designs. Behavioral Genetics, 30, 147–158.Google Scholar
  103. Posthuma, D., de Geus, E. J.C., Neale, M. C., Pol, H. E.H., Baare, W. E.C., Kahn, R. S., et al. (2000). Multivariate genetic analysis of brain structure in an extended twin design. Behavior Genetics, 30, 311–319.PubMedGoogle Scholar
  104. Posthuma, D., de Geus, E. J., Baare, W. F., Hulshoff Pol, H. E., Kahn, R. S., & Boomsma, D. I. (2002). The association between brain volume and intelligence is of genetic origin. Nature Neuroscience, 5, 83–84.PubMedGoogle Scholar
  105. Rakic, P., Bourgeois, J. P., & Goldman-Rakic, P. S. (1994). Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness. Progression in Brain Research, 102, 227–243.Google Scholar
  106. Raz, N., Torres, I. J., Briggs, S. D., Spencer, W. D., Thornton, A. E., Loken, W. J., et al. (1995). Selective neuroanatomic abnormalities in Down’s syndrome and their cognitive correlates: evidence from MRI morphometry. Neurology, 45, 356–366.PubMedGoogle Scholar
  107. Reiss, A. L., Eliez, S., Schmitt, J. E., Straus, E., Lai, Z., Jones, W., et al. (2000). IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study. Journal of Cognitive Neuroscience, 12(Suppl 1), 65–73.PubMedGoogle Scholar
  108. Reiss, A. L., Eckert, M. A., Rose, F. E., Karchemskiy, A., Kesler, S., Chang, M., et al. (2004). An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome. Journal of Neuroscience, 24, 5009–5015.PubMedGoogle Scholar
  109. Reveley, A. M., Reveley, M. A., Chitkara, B. & Clifford, C. (1984). The genetic basis of cerebral ventricular volume. Psychiatry Research, 13, 261–266.PubMedGoogle Scholar
  110. Rosas, H. D., Goodman, J., Chen, Y. I., Jenkins, B. G., Kennedy, D. N., Makris, N., et al. (2001). Striatal volume loss in HD as measured by MRI and the influence of CAG repeat. Neurology, 57, 1025–1028.PubMedGoogle Scholar
  111. Rosas, H. D., Koroshetz, W. J., Chen, Y. I., Skeuse, C., Vangel, M., Cudkowicz, M. E., et al. (2003). Evidence for more widespread cerebral pathology in early HD: An MRI-based morphometric analysis. Neurology, 60, 1615–1620.PubMedGoogle Scholar
  112. Rosas, H. D., Hevelone, N. D., Zaleta, A. K., Greve, D. N., Salat, D. H., & Fischl B. (2005). Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology, 65, 745–747.PubMedGoogle Scholar
  113. Santos, K. F., Mazzola, T. N., & Carvalho, H. F. (2005). The prima donna of epigenetics: The regulation of gene expression by DNA methylation. Brazilian Journal of Medical and Biological Research, 38, 1531–1541.PubMedGoogle Scholar
  114. Scamvougeras, A., Kigar, D. L., Jones, D., Weinberger, D. R., & Witelson, S. F. (2003). Size of the human corpus callosum is genetically determined: an MRI study in mono and dizygotic twins. Neuroscience Letters, 338, 91–94.PubMedGoogle Scholar
  115. Schmitt, J. E., Eliez, S., Warsofsky, I. S., Bellugi, U., & Reiss, A. L. (2001a). Enlarged cerebellar vermis in Williams syndrome. Journal of Psychiatric Research, 35, 225–229.PubMedGoogle Scholar
  116. Schmitt, J. E., Eliez, S., Warsofsky, I. S., Bellugi, U., & Reiss, A. L. (2001b). Corpus callosum morphology of Williams syndrome: Relation to genetics and behavior. Developmental Medicine and Child Neurology, 43, 155–159.PubMedGoogle Scholar
  117. Schmitt, J. E., Watts, K., Eliez, S., Bellugi, U., Galaburda, A. M., & Reiss, A. L. (2002). Increased gyrification in Williams syndrome: Evidence using 3D MRI methods. Developmental Medicine and Child Neurology, 44, 292–295.PubMedGoogle Scholar
  118. Simon, T. J., Ding, L., Bish, J. P., McDonald-McGinn, D. M., Zackai, E. H., & Gee J. (2005). Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study. Neuroimage, 25, 169–180.PubMedGoogle Scholar
  119. Sowell, E. R., Trauner, D. A., Gamst, A., & Jernigan, T. L. (2002). Development of cortical and subcortical brain structures in childhood and adolescence: A structural MRI study. Developmental Medicine and Child Neurology, 44, 4–16.PubMedGoogle Scholar
  120. Sugama, S., Bingham, P. M., Wang, P. P., Moss, E. M., Kobayashi, H., & Eto Y. (2000). Morphometry of the head of the caudate nucleus in patients with velocardiofacial syndrome (del 22q11.2). Acta Paediatrica, 89, 546–549.PubMedGoogle Scholar
  121. Sullivan, E. V., Pfefferbaum, A., Swan, G. E., & Carmelli D. (2001). Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment. Hippocampus, 11, 754–762.PubMedGoogle Scholar
  122. Sullivan, E. V., Rosenbloom, M., Serventi, K. L., & Pfefferbaum, A. (2004). Effects of age and sex on volumes of the thalamus, pons, and cortex. Neurobiology of Aging, 25, 185–192.PubMedGoogle Scholar
  123. Swillen, A., Devriendt, K., Legius, E., Prinzie, P., Vogels, A., Ghesquiere, P., et al. (1999). The behavioural phenotype in velo-cardio-facial syndrome (VCFS): From infancy to adolescence. Genetic Counseling, 10, 79–88.PubMedGoogle Scholar
  124. Szeszko, P. R., Lipsky, R., Mentschel, C., Robinson, D., Gunduz-Bruce, H., Sevy, S., et al. (2005). Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Molecular Psychiatry, 10, 631–636.PubMedGoogle Scholar
  125. Teipel, S. J., Schapiro, M. B., Alexander, G. E., Krasuski, J. S., Horwitz, B., Hoehne, C., et al. (2003). Relation of corpus callosum and hippocampal size to age in nondemented adults with Down’s syndrome. American Journal of Psychiatry, 160, 1870–1878.PubMedGoogle Scholar
  126. Teipel, S. J., Alexander, G. E., Schapiro, M. B., Moller, H. J., Rapoport, S. I., & Hampel H. (2004). Age-related cortical grey matter reductions in non-demented Down’s syndrome adults determined by MRI with voxel-based morphometry. Brain, 127, 811–824.PubMedGoogle Scholar
  127. Thieben, M. J., Duggins, A. J., Good, C. D., Gomes, L., Mahant, N., Richards, F., et al. (2002). The distribution of structural neuropathology in pre-clinical Huntington’s disease. Brain, 125, 1815–1828.PubMedGoogle Scholar
  128. Thompson, P. M., Cannon, T. D., Narr, K. L., van Erp, T., Poutanen, V. P., Huttunen, M., et al. (2001). Genetic influences on brain structure. Nature Neuroscience, 4, 1253–1258.PubMedGoogle Scholar
  129. Thompson, P. M., Lee, A. D., Dutton, R. A., Geaga, J. A., Hayashi, K. M., Eckert, M. A., et al. (2005). Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. Journal of Neuroscience, 25, 4146–4158.PubMedGoogle Scholar
  130. Toga, A. W., & Thompson, P. M. (2004). Genetics of Brain Structure and Intelligence. Annual Review of Neuroscience, 28, 1–23.Google Scholar
  131. Toga, A. W., Thompson, P. M., & Sowell, E. R. (2006). Mapping brain maturation. Trends in Neurosciences, 29, 148–159.PubMedGoogle Scholar
  132. Tomaiuolo, F., Di Paola, M., Caravale, B., Vicari, S., Petrides, M., & Caltagirone C. (2002). Morphology and morphometry of the corpus callosum in Williams syndrome: A T1-weighted MRI study. Neuroreport, 13, 2281–2284.PubMedGoogle Scholar
  133. van Amelsvoort, T., Daly, E., Henry, J., Robertson, D., Nguyen, V., Owen, M., et al. (2004). Brain anatomy in adults with velocardiofacial syndrome with and without schizophrenia: preliminary results of a structural magnetic resonance imaging study. Archives of General Psychiatry, 61, 1085–1096.PubMedGoogle Scholar
  134. Vargha-Khadem, F., Watkins, K., Alcock, K., Fletcher, P., & Passingham, R. (1995). Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proceedings of the National Academy of Sciences of the United States of America, 92, 930–933.PubMedGoogle Scholar
  135. Vink, J. M., & Boomsma, D. I. (2002). Gene finding strategies. Biological Psychology, 61, 53–71.PubMedGoogle Scholar
  136. Wang, P. P., Hesselink, J. R., Jernigan, T. L., Doherty, S., & Bellugi, U. (1992). Specific neurobehavioral profile of Williams’ syndrome is associated with neocerebellar hemispheric preservation. Neurology, 42, 1999–2002.PubMedGoogle Scholar
  137. Watkins, K. E., Vargha-Khadem, F., Ashburner, J., Passingham, R. E., Connelly, A., Friston, K. J., et al. (2002). MRI analysis of an inherited speech and language disorder: structural brain abnormalities. Brain, 125, 465–478.PubMedGoogle Scholar
  138. Weickert, C. S., Hyde, T. M., Lipska, B. K., Herman, M. M., Weinberger, D. R., & Kleinman, J. E. (2003). Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Molecular Psychiatry, 8, 592–610.PubMedGoogle Scholar
  139. Weis, S., Weber, G., Neuhold, A., & Rett, A. (1991). Down syndrome: MR quantification of brain structures and comparison with normal control subjects. AJNR American Journal of Neuroradiology, 12, 1207–1211.PubMedGoogle Scholar
  140. White, N. S., Alkire, M. T., & Haier, R. J. (2003). A voxel-based morphometric study of nondemented adults with Down Syndrome. Neuroimage, 20, 393–403.PubMedGoogle Scholar
  141. White, T., Andreasen, N. C., & Nopoulos P. (2002). Brain volumes and surface morphology in monozygotic twins. Cerebral Cortex, 12, 486–493.PubMedGoogle Scholar
  142. Woods, R. P., Freimer, N. B., De Young, J. A., Fears, S. C., Sicotte, N. L., Service, S. K., et al. (2006). Normal Variants of Microcephalin and ASPM Do Not Account for Brain Size Variability. Human Molecular Genetics, 15, 2025–2029.PubMedGoogle Scholar
  143. Wright, I. C., Sham, P., Murray, R. M., Weinberger, D. R., & Bullmore, E. T. (2002). Genetic contributions to regional variability in human brain structure: methods and preliminary results. Neuroimage, 17, 256–271.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jiska S. Peper
    • 1
  • Marcel P. Zwiers
    • 2
    • 3
  • Dorret I. Boomsma
    • 4
  • Reneacute S. Kahn
    • 5
  • Hilleke E. Hulshoff Pol
    • 5
  1. 1.Department of PsychiatryUniversity Medical CenterUtrechtThe Netherlands
  2. 2.F.C. Donders Center for Cognitive NeuroscienceNijmegenNetherlands
  3. 3.Psychiatry DepartmentRadboud University, Nijmegen Medical CenterNijmegenNetherlands
  4. 4.Department of Biological PsychologyVrije UniversiteitAmsterdamNetherlands
  5. 5.Department of PsychiatryRudolf Magnus Institute of Neuroscience, University Medical CenterUtrechtNetherlands

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