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Animal Models and Human Neuropsychiatric Disorders

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Abstract

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.

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References

  • Althoff RR, Faraone SV, Rettew DC, Morley CP, Hudziak JJ (2005) Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder. Bipolar Disord 7:598–609

    Article  PubMed  CAS  Google Scholar 

  • Anderson B (1994) Role for animal research in the investigation of human mental retardation. Am J Ment Retard 99:50–59

    PubMed  CAS  Google Scholar 

  • 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):596–603

    Article  PubMed  Google Scholar 

  • 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 5:544–553

    Article  PubMed  Google Scholar 

  • 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 11:109–117

    Article  PubMed  Google Scholar 

  • Binet A, Henri V (1895) La Psychologie individuelle. Annee Psychol 2:411–465

    Google Scholar 

  • 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 62:537–551

    Article  PubMed  CAS  Google Scholar 

  • Bouchard TJ Jr, Loehlin JC (2001) Genes, evolution, and personality. Behav Genet 31:243–273

    Article  PubMed  Google Scholar 

  • Cattell JM (1890) Mental tests and measurements. Mind 15:373–380

    Article  Google Scholar 

  • Clement Y, Calatayud F, Belzung C (2002) Genetic basis of anxiety-like behaviour: a critical review. Brain Res Bull 57:57–71

    Article  PubMed  Google Scholar 

  • Cooper RM, Zubek JP (1958) Effects of enriched and restricted early environments on the learning ability of bright and dull rats. Can J Psychol 12:159–164

    PubMed  CAS  Google Scholar 

  • Cowan WM, Harter DH, Kandel ER (2000) The emergence of modern neuroscience: some implications for neurology and psychiatry. Annu Rev Neurosci 23:343–391

    Article  PubMed  CAS  Google Scholar 

  • Crabbe JC, Wahlsten D, Dudek BC (1999) Genetics of mouse behavior: interactions with laboratory environment. Science 284:1670–1672

    Article  PubMed  CAS  Google Scholar 

  • 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 11:446–458

    Article  PubMed  CAS  Google Scholar 

  • 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 31:197–211

    Article  PubMed  CAS  Google Scholar 

  • 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) 132:107–124

    Article  CAS  Google Scholar 

  • Dalvi A, Lucki I (1999) Murine models of depression. Psychopharmacol (Berl) 147:4–6

    Google Scholar 

  • Darwin C (1872) The expression of the emotions in man and animals. John Murray, London

    Google Scholar 

  • Edamura K, Sasai H (1998) No self-injurious behavior was found in HPRT-deficient mice treated with 9-ethyladenine. Pharmacol Biochem Behav 61:175–179

    Article  PubMed  CAS  Google Scholar 

  • 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 93:5307–5312

    Article  PubMed  CAS  Google Scholar 

  • Estes WK, Koch S, MacCorquodale K, Meehl PE, Mueller CG, Schoenfeld WN, Verplanck WS (1954) Modern learning theory. Appletob-Centiry-Crofts, Inc., New York

    Google Scholar 

  • 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 25–44

    Chapter  Google Scholar 

  • Gardner H (1985) The mind’s new science: a history of the cognitive revolution. Basic Books, Inc., New York

    Google Scholar 

  • 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 45–68

    Chapter  Google Scholar 

  • 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 163:857–864

    Article  PubMed  Google Scholar 

  • 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 237–264

    Chapter  Google Scholar 

  • 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 69–84

    Chapter  Google Scholar 

  • Jefress LA (ed) (1951) Cerebral mechanisms in behavior. In: The Hixon symposium. Wiley, New York

  • Jennings HS (1906) Behavior of lower organisms. Columbia University Press, New York

    Google Scholar 

  • Kallman FJ (1959) The genetics of mental illness. In: Arieti S (ed) American handbook of psychiatry. Basic Books, New York

    Google Scholar 

  • Kendler KS, Gatz M, Gardner CO, Pedersen NL (2006) A Swedish national twin study of lifetime major depression. Am J Psychiatry 163:109–114

    Article  PubMed  Google Scholar 

  • Kordower JH, Gash DM (1988) Animal models of age- and disease-related cognitive decline: perspectives on the models and therapeutic strategies. Neurobiol Aging 9:685–689

    Article  PubMed  CAS  Google Scholar 

  • Kraepelin E (1883) Compendium der Psychiatrie zum Gebrauche für Studirende und Aerzte. Abel Verlag, Leipzig

    Google Scholar 

  • Lejeune J, Gautier M, Turpin R (1959) Etudes des chromosomes somatiques de neuf enfants mongoliens. C R Acad Sci 248:1721

    CAS  Google Scholar 

  • 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 99:16859–16864

    Article  PubMed  CAS  Google Scholar 

  • Lloyd Morgan C (1894). An introduction to comparative psychology. W. Scott, London

    Google Scholar 

  • Loeb J (1918/1973) Forced movements, tropisms, and animal conduct (reprinted 1973). Dover Publications, New York

  • Lubbock J (1884) Ants, bees, and wasps. D. Appleton & Co, New York

    Google Scholar 

  • Lubs HA (1969) A marker X chromosome. Am J Hum Genet 21:231–244

    PubMed  CAS  Google Scholar 

  • 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 34:41–50

    Article  PubMed  Google Scholar 

  • Mathiesen KS, Tambs K (1999) The EAS temperament questionnaire–factor structure, age trends, reliability, and stability in a Norwegian sample. J Child Psychol Psychiatry 40:431–439

    Article  PubMed  CAS  Google Scholar 

  • McKinney WT Jr, Bunney WE Jr (1969) Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 21:240–248

    PubMed  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260

    Article  Google Scholar 

  • Morris RGM, Garrud P, Rawlins JNP, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nat (Lond) 297:681–683

    Article  CAS  Google Scholar 

  • Pavlov IP (1941) Lectures on conditioned reflexes. Conditioned reflexes and psychiatry (Trans. WH Gantt), vol II. International Publishing Co, New York

  • 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 93:13090–13095

    Article  PubMed  CAS  Google Scholar 

  • Plomin R (2001) The genetics of g in human and mouse. Nat Rev Neurosci 2:136–141

    Article  PubMed  CAS  Google Scholar 

  • 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 183–202

    Chapter  Google Scholar 

  • Plomin R, Rowe DC (1977) A twin study of temperament in young children. J Psychol 97:107–113

    PubMed  CAS  Google Scholar 

  • 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 3–15

    Chapter  Google Scholar 

  • 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 31:567–579

    Article  PubMed  CAS  Google Scholar 

  • 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 141–162

    Chapter  Google Scholar 

  • 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 201:366–377

    PubMed  CAS  Google Scholar 

  • Risch N et al (1999) A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 65:493–507

    Article  PubMed  CAS  Google Scholar 

  • Romanes GS (1881) Animal intelligence. Kegan Paul Trench & Co, London

    Google Scholar 

  • Saudino KJ (2005) Behavioral genetics and child temperament. J Dev Behav Pediatr 26:214–223

    Article  PubMed  Google Scholar 

  • 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 68:723–733

    Article  PubMed  CAS  Google Scholar 

  • 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 35:243–254

    Article  PubMed  CAS  Google Scholar 

  • Sherrington C (1906/1947) The integrative action of the nervous system (reprinted 1947). Yale University Press, New Haven

  • 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 46:1317–1326

    Article  PubMed  Google Scholar 

  • 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 10:553–562

    Article  PubMed  CAS  Google Scholar 

  • Spearman CE (1904) ‘General intelligence,’ objectively determined and measured. Am J Psychol 15:201–293

    Article  Google Scholar 

  • The Dutch-Belgian Fragile X Consortium (1994) Fmr1 knockout mice: a model to study fragile X mental retardation. Cell 78:23–33

    Google Scholar 

  • Thompson R, Crinella FM, Yu J (1990) Brain mechanisms in problem solving and intelligence. Plenum, New York

    Google Scholar 

  • Tryon RC (1940) Genetic differences in maze-learning ability in rats. Yearbook Natl Soc Stud Educ 39:111–119

    Google Scholar 

  • Wolfer DP, Crusio WE, Lipp HP (2002) Knockout mice: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci 25:336–340

    Article  PubMed  CAS  Google Scholar 

  • Wolfer DP, Litvin O, Morf S, Nitsch RM, Lipp HP, Wurbel H (2004) Laboratory animal welfare: cage enrichment and mouse behaviour. Nature 432:821–822

    Article  PubMed  CAS  Google Scholar 

  • Wu CL, Melton DW (1993) Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3:235–240

    Article  PubMed  CAS  Google Scholar 

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Fisch, G.S. Animal Models and Human Neuropsychiatric Disorders. Behav Genet 37, 1–10 (2007). https://doi.org/10.1007/s10519-006-9117-0

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