Behavior Genetics

, Volume 37, Issue 1, pp 1–10 | Cite as

Animal Models and Human Neuropsychiatric Disorders

  • Gene S. Fisch
Original Paper


Humans have long distinguished themselves from other living organisms. Therefore, to make use of animal models for neuropsychiatric disorders, it is important to acknowledge what has changed historically. Darwin argued that there was continuity in mind between humans and nonhuman species, and animal experimental psychologists and others have debated the existence of consciousness and mentality in animals ever since. Those trained in the associationist tradition sought to eliminate the concept of mind in favor of an empiricial, behavioral approach; others trained in the introspectionist tradition sought to include mental abilities as an integral part of comparative animal psychology. The waning of behaviorism and ascendance of cognitive psychology in the mid-twentieth century renewed interest in the notion of consciousness and mind in nonhuman organisms, particularly as they related to learning impairment and neurobehavioral disorders. Moreover, advances in molecular genetics and technology facilitated development of genetically modified mouse strains that could be used to examine cognitive deficits and psychopathology. However, genetic modifications to individual genes that produce behavioral dysfunction in the mouse have not always provided clear results. In part, this is likely due to the influence of genes in addition to the targeted gene, sometimes resulting in paradoxical effects. I also examine other issues created by the use of nonhuman models of human disorders, including: language, the effect of background genetic strains, genetic-environmental interactions, and the problems associated with the complex genetics needed to produce similarly complex behavioral phenotypes.


Genetics Behavior Mouse models Transgenics Knockout mice Mental retardation Psychopathology 


  1. Althoff RR, Faraone SV, Rettew DC, Morley CP, Hudziak JJ (2005) Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder. Bipolar Disord 7:598–609PubMedCrossRefGoogle Scholar
  2. Anderson B (1994) Role for animal research in the investigation of human mental retardation. Am J Ment Retard 99:50–59PubMedGoogle Scholar
  3. Antshel KM, Fremont W, Roizen NJ, Shprintzen R, Higgins AM, Dhamoon A, Kates WR (2006) ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome. J Am Acad Child Adolesc Psychiatry 45(5):596–603PubMedCrossRefGoogle Scholar
  4. Bartels M, Rietveld MJ, Van Baal GC, Boomsma DI (2002) Heritability of educational achievement in 12-year-olds and the overlap with cognitive ability. Twin Res 5:544–553PubMedCrossRefGoogle Scholar
  5. Bearden CE, Jawad AF, Lynch DR, Monterossso JR, Sokol S, McDonald-McGinn DM, Saitta SC, Harris SE, Moss E, Wang PP, Zackai E, Emanuel BS, Simon TJ (2005) Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion Syndrome. Child Neuropsychol 11:109–117PubMedCrossRefGoogle Scholar
  6. Binet A, Henri V (1895) La Psychologie individuelle. Annee Psychol 2:411–465Google Scholar
  7. Boer F, Westenberg PM (1994) The factor structure of the Buss and Plomin EAS Temperament Survey (parental ratings) in a Dutch sample of elementary school children. J Pers Assess 62:537–551PubMedCrossRefGoogle Scholar
  8. Bouchard TJ Jr, Loehlin JC (2001) Genes, evolution, and personality. Behav Genet 31:243–273PubMedCrossRefGoogle Scholar
  9. Cattell JM (1890) Mental tests and measurements. Mind 15:373–380CrossRefGoogle Scholar
  10. Clement Y, Calatayud F, Belzung C (2002) Genetic basis of anxiety-like behaviour: a critical review. Brain Res Bull 57:57–71PubMedCrossRefGoogle Scholar
  11. Cooper RM, Zubek JP (1958) Effects of enriched and restricted early environments on the learning ability of bright and dull rats. Can J Psychol 12:159–164PubMedGoogle Scholar
  12. Cowan WM, Harter DH, Kandel ER (2000) The emergence of modern neuroscience: some implications for neurology and psychiatry. Annu Rev Neurosci 23:343–391PubMedCrossRefGoogle Scholar
  13. Crabbe JC, Wahlsten D, Dudek BC (1999) Genetics of mouse behavior: interactions with laboratory environment. Science 284:1670–1672PubMedCrossRefGoogle Scholar
  14. Craddock N, Owen MJ, O’Donovan MC (2006) The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry 11:446–458PubMedCrossRefGoogle Scholar
  15. Crawley JN, Paylor R (1997) A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm Behav 31:197–211PubMedCrossRefGoogle Scholar
  16. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R (1997) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacol (Berl) 132:107–124CrossRefGoogle Scholar
  17. Dalvi A, Lucki I (1999) Murine models of depression. Psychopharmacol (Berl) 147:4–6Google Scholar
  18. Darwin C (1872) The expression of the emotions in man and animals. John Murray, LondonGoogle Scholar
  19. Edamura K, Sasai H (1998) No self-injurious behavior was found in HPRT-deficient mice treated with 9-ethyladenine. Pharmacol Biochem Behav 61:175–179PubMedCrossRefGoogle Scholar
  20. Engle SJ, Stockelman MG, Chen J, Boivin G, Yum MN, Davies PM, Ying MY, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA (1996) Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc Natl Acad Sci USA 93:5307–5312PubMedCrossRefGoogle Scholar
  21. Estes WK, Koch S, MacCorquodale K, Meehl PE, Mueller CG, Schoenfeld WN, Verplanck WS (1954) Modern learning theory. Appletob-Centiry-Crofts, Inc., New YorkGoogle Scholar
  22. Flint J (2006) Transgenic mouse models and human psychiatric disease. In: Fisch GS, Flint J (eds) Transgenic and knockout models of neuropsychiatric disorders. Humana Press, Totowa, pp 25–44CrossRefGoogle Scholar
  23. Gardner H (1985) The mind’s new science: a history of the cognitive revolution. Basic Books, Inc., New YorkGoogle Scholar
  24. Hayes LJ, Delgado D (2006) Transgenic and knockout mouse models: the problem of language. In: Fisch GS, Flint J (eds) Transgenic and knockout models of neuropsychiatric disorders. Humana Press, Totowa, pp 45–68CrossRefGoogle Scholar
  25. Hettema JM, Neale MC, Myers JM, Prescott CA, Kendler KS (2006) A population-based twin study of the relationship between neuroticism and internalizing disorders. Am J Psychiatry 163:857–864PubMedCrossRefGoogle Scholar
  26. Holmes A, Cryan JF (2006) Modeling human anxiety and depression in mutant mice. In: Fisch GS, Flint J (eds) Transgenic and knockout models of neuropsychiatric disorders. Humana Press, Totowa, pp 237–264CrossRefGoogle Scholar
  27. Humby T, Wilkinson L (2006) If only they could talk: genetic mouse models for psychiatric disorders. In: Fisch GS, Flint J (eds) Transgenic and knockout models of neuropsychiatric disorders. Humana Press, Totowa, pp 69–84CrossRefGoogle Scholar
  28. Jefress LA (ed) (1951) Cerebral mechanisms in behavior. In: The Hixon symposium. Wiley, New YorkGoogle Scholar
  29. Jennings HS (1906) Behavior of lower organisms. Columbia University Press, New YorkGoogle Scholar
  30. Kallman FJ (1959) The genetics of mental illness. In: Arieti S (ed) American handbook of psychiatry. Basic Books, New YorkGoogle Scholar
  31. Kendler KS, Gatz M, Gardner CO, Pedersen NL (2006) A Swedish national twin study of lifetime major depression. Am J Psychiatry 163:109–114PubMedCrossRefGoogle Scholar
  32. Kordower JH, Gash DM (1988) Animal models of age- and disease-related cognitive decline: perspectives on the models and therapeutic strategies. Neurobiol Aging 9:685–689PubMedCrossRefGoogle Scholar
  33. Kraepelin E (1883) Compendium der Psychiatrie zum Gebrauche für Studirende und Aerzte. Abel Verlag, LeipzigGoogle Scholar
  34. Lejeune J, Gautier M, Turpin R (1959) Etudes des chromosomes somatiques de neuf enfants mongoliens. C R Acad Sci 248:1721Google Scholar
  35. Liu H, Abecasis GR, Heath SC, Knowles A, Demars S, Chen YJ, Roos JL, Rapoport JL, Gogos JA, Karayiorgou M (2002) Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc Natl Acad Sci USA 99:16859–16864PubMedCrossRefGoogle Scholar
  36. Lloyd Morgan C (1894). An introduction to comparative psychology. W. Scott, LondonGoogle Scholar
  37. Loeb J (1918/1973) Forced movements, tropisms, and animal conduct (reprinted 1973). Dover Publications, New YorkGoogle Scholar
  38. Lubbock J (1884) Ants, bees, and wasps. D. Appleton & Co, New YorkGoogle Scholar
  39. Lubs HA (1969) A marker X chromosome. Am J Hum Genet 21:231–244PubMedGoogle Scholar
  40. Luciano M, Wright MJ, Geffen GM, Geffen LB, Smith GA, Martin NG (2004) A genetic investigation of the covariation among inspection time, choice reaction time, and IQ subtest scores. Behav Genet 34:41–50PubMedCrossRefGoogle Scholar
  41. Mathiesen KS, Tambs K (1999) The EAS temperament questionnaire–factor structure, age trends, reliability, and stability in a Norwegian sample. J Child Psychol Psychiatry 40:431–439PubMedCrossRefGoogle Scholar
  42. McKinney WT Jr, Bunney WE Jr (1969) Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 21:240–248PubMedGoogle Scholar
  43. Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260CrossRefGoogle Scholar
  44. Morris RGM, Garrud P, Rawlins JNP, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nat (Lond) 297:681–683CrossRefGoogle Scholar
  45. Pavlov IP (1941) Lectures on conditioned reflexes. Conditioned reflexes and psychiatry (Trans. WH Gantt), vol II. International Publishing Co, New YorkGoogle Scholar
  46. Pham CT, MacIvor DM, Hug BA, Heusel JW, Ley TJ (1996) Long-range disruption of gene expression by a selectable marker cassette. Proc Natl Acad Sci USA 93:13090–13095PubMedCrossRefGoogle Scholar
  47. Plomin R (2001) The genetics of g in human and mouse. Nat Rev Neurosci 2:136–141PubMedCrossRefGoogle Scholar
  48. Plomin R (2003) General cognitive ability. In: Plomin R, deFries JC, Craig IW, McGuffin P (eds) Behavioral genetics in the postgenomic era. American Psychological Association, Washington, pp 183–202CrossRefGoogle Scholar
  49. Plomin R, Rowe DC (1977) A twin study of temperament in young children. J Psychol 97:107–113PubMedGoogle Scholar
  50. Plomin R, deFries JC, Craig IW, McGuffin P (2003) Behavior genetics. In: Plomin R, deFries JC, Craig IW, McGuffin P (eds) Behavioral genetics in the postgenomic era. American Psychological Association, Washington, pp 3–15CrossRefGoogle Scholar
  51. Posthuma D, Neale MC, Boomsma DI, de Geus EJ (2001) Are smarter brains running faster? Heritability of alpha peak frequency, IQ, and their interrelation. Behav Genet 31:567–579PubMedCrossRefGoogle Scholar
  52. Posthuma D, de Geus EJC, Boomsma DI (2003) Genetic contributions to anatomical, behavioral, and neurophsyiological indices of cognition. In: Plomin R, deFries JC, Craig IW, McGuffin P (eds) Behavioral genetics in the postgenomic era. American Psychological Association, Washington, pp 141–162CrossRefGoogle Scholar
  53. Rijli FM, Dolle P, Fraulob VML, Chambon P (1994) Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression. Dev Dyn 201:366–377PubMedGoogle Scholar
  54. Risch N et al (1999) A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 65:493–507PubMedCrossRefGoogle Scholar
  55. Romanes GS (1881) Animal intelligence. Kegan Paul Trench & Co, LondonGoogle Scholar
  56. Saudino KJ (2005) Behavioral genetics and child temperament. J Dev Behav Pediatr 26:214–223PubMedCrossRefGoogle Scholar
  57. Saudino KJ, McGuire S, Reiss D, Hetherington EM, Plomin R (1995) Parent ratings of EAS temperaments in twins, full siblings, half siblings, and step siblings. J Pers Soc Psychol 68:723–733PubMedCrossRefGoogle Scholar
  58. Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002) Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35:243–254PubMedCrossRefGoogle Scholar
  59. Sherrington C (1906/1947) The integrative action of the nervous system (reprinted 1947). Yale University Press, New HavenGoogle Scholar
  60. Silberg JL, Bulik CM (2005) The developmental association between eating disorders symptoms and symptoms of depression and anxiety in juvenile twin girls. J Child Psychol Psychiatry 46:1317–1326PubMedCrossRefGoogle Scholar
  61. Sobin C, Kiley-Brabeck K, Karayiorgou M (2005) Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome. Mol Psychiatry 10:553–562PubMedCrossRefGoogle Scholar
  62. Spearman CE (1904) ‘General intelligence,’ objectively determined and measured. Am J Psychol 15:201–293CrossRefGoogle Scholar
  63. The Dutch-Belgian Fragile X Consortium (1994) Fmr1 knockout mice: a model to study fragile X mental retardation. Cell 78:23–33Google Scholar
  64. Thompson R, Crinella FM, Yu J (1990) Brain mechanisms in problem solving and intelligence. Plenum, New YorkGoogle Scholar
  65. Tryon RC (1940) Genetic differences in maze-learning ability in rats. Yearbook Natl Soc Stud Educ 39:111–119Google Scholar
  66. Wolfer DP, Crusio WE, Lipp HP (2002) Knockout mice: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci 25:336–340PubMedCrossRefGoogle Scholar
  67. Wolfer DP, Litvin O, Morf S, Nitsch RM, Lipp HP, Wurbel H (2004) Laboratory animal welfare: cage enrichment and mouse behaviour. Nature 432:821–822PubMedCrossRefGoogle Scholar
  68. Wu CL, Melton DW (1993) Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3:235–240PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Yeshiva UniversityNew YorkUSA
  2. 2.CUNY/Lehman CollegeBronxUSA

Personalised recommendations