Skip to main content
PMC home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 Feb 28;358(1430):303–314. doi: 10.1098/rstb.2002.1198

Identifying neurocognitive phenotypes in autism.

Helen Tager-Flusberg 1, Robert M Joseph 1
PMCID: PMC1201482  NIHMSID: NIHMS4242  PMID: 12639328

Abstract

Autism is a complex disorder that is heterogeneous both in its phenotypic expression and its etiology. The search for genes associated with autism and the neurobiological mechanisms that underlie its behavioural symptoms has been hampered by this heterogeneity. Recent studies indicate that within autism, there may be distinct subgroups that can be defined based on differences in neurocognitive profiles. This paper presents evidence for two kinds of subtypes in autism that are defined on the basis of language profiles and on the basis of cognitive profiles. The implications for genetic and neurobiological studies of these subgroups are discussed, with special reference to evidence relating these cognitive phenotypes to volumetric studies of brain size and organization in autism.

Full Text

The Full Text of this article is available as a PDF (236.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amir R. E., Van den Veyver I. B., Wan M., Tran C. Q., Francke U., Zoghbi H. Y. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185–188. doi: 10.1038/13810. [DOI] [PubMed] [Google Scholar]
  2. Bailey A., Le Couteur A., Gottesman I., Bolton P., Simonoff E., Yuzda E., Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995 Jan;25(1):63–77. doi: 10.1017/s0033291700028099. [DOI] [PubMed] [Google Scholar]
  3. Bailey A., Palferman S., Heavey L., Le Couteur A. Autism: the phenotype in relatives. J Autism Dev Disord. 1998 Oct;28(5):369–392. doi: 10.1023/a:1026048320785. [DOI] [PubMed] [Google Scholar]
  4. Bailey A., Phillips W., Rutter M. Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. J Child Psychol Psychiatry. 1996 Jan;37(1):89–126. doi: 10.1111/j.1469-7610.1996.tb01381.x. [DOI] [PubMed] [Google Scholar]
  5. Bartak L., Rutter M., Cox A. A comparative study of infantile autism and specific development receptive language disorder. I. The children. Br J Psychiatry. 1975 Feb;126:127–145. doi: 10.1192/bjp.126.2.127. [DOI] [PubMed] [Google Scholar]
  6. Bartlett Christopher W., Flax Judy F., Logue Mark W., Vieland Veronica J., Bassett Anne S., Tallal Paula, Brzustowicz Linda M. A major susceptibility locus for specific language impairment is located on 13q21. Am J Hum Genet. 2002 Jun 4;71(1):45–55. doi: 10.1086/341095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barton M., Volkmar F. How commonly are known medical conditions associated with autism? J Autism Dev Disord. 1998 Aug;28(4):273–278. doi: 10.1023/a:1026052417561. [DOI] [PubMed] [Google Scholar]
  8. Bedore L. M., Leonard L. B. Specific language impairment and grammatical morphology: a discriminant function analysis. J Speech Lang Hear Res. 1998 Oct;41(5):1185–1192. doi: 10.1044/jslhr.4105.1185. [DOI] [PubMed] [Google Scholar]
  9. Bishop Dorothy V. M., Norbury Courtenay Frazier. Exploring the borderlands of autistic disorder and specific language impairment: a study using standardised diagnostic instruments. J Child Psychol Psychiatry. 2002 Oct;43(7):917–929. doi: 10.1111/1469-7610.00114. [DOI] [PubMed] [Google Scholar]
  10. Bolton P., Macdonald H., Pickles A., Rios P., Goode S., Crowson M., Bailey A., Rutter M. A case-control family history study of autism. J Child Psychol Psychiatry. 1994 Jul;35(5):877–900. doi: 10.1111/j.1469-7610.1994.tb02300.x. [DOI] [PubMed] [Google Scholar]
  11. Clark M. M., Plante E. Morphology of the inferior frontal gyrus in developmentally language-disordered adults. Brain Lang. 1998 Feb 1;61(2):288–303. doi: 10.1006/brln.1997.1864. [DOI] [PubMed] [Google Scholar]
  12. Cohen I. L. An artificial neural network analogue of learning in autism. Biol Psychiatry. 1994 Jul 1;36(1):5–20. doi: 10.1016/0006-3223(94)90057-4. [DOI] [PubMed] [Google Scholar]
  13. Davidovitch M., Patterson B., Gartside P. Head circumference measurements in children with autism. J Child Neurol. 1996 Sep;11(5):389–393. doi: 10.1177/088307389601100509. [DOI] [PubMed] [Google Scholar]
  14. Dawson Geraldine, Webb Sara, Schellenberg Gerard D., Dager Stephen, Friedman Seth, Aylward Elizabeth, Richards Todd. Defining the broader phenotype of autism: genetic, brain, and behavioral perspectives. Dev Psychopathol. 2002 Summer;14(3):581–611. doi: 10.1017/s0954579402003103. [DOI] [PubMed] [Google Scholar]
  15. Dollaghan C., Campbell T. F. Nonword repetition and child language impairment. J Speech Lang Hear Res. 1998 Oct;41(5):1136–1146. doi: 10.1044/jslhr.4105.1136. [DOI] [PubMed] [Google Scholar]
  16. Elgar K., Campbell R. Annotation: the cognitive neuroscience of face recognition: implications for developmental disorders. J Child Psychol Psychiatry. 2001 Sep;42(6):705–717. doi: 10.1111/1469-7610.00767. [DOI] [PubMed] [Google Scholar]
  17. Ellis Weismer S., Tomblin J. B., Zhang X., Buckwalter P., Chynoweth J. G., Jones M. Nonword repetition performance in school-age children with and without language impairment. J Speech Lang Hear Res. 2000 Aug;43(4):865–878. doi: 10.1044/jslhr.4304.865. [DOI] [PubMed] [Google Scholar]
  18. Fidler D. J., Bailey J. N., Smalley S. L. Macrocephaly in autism and other pervasive developmental disorders. Dev Med Child Neurol. 2000 Nov;42(11):737–740. doi: 10.1017/s0012162200001365. [DOI] [PubMed] [Google Scholar]
  19. Filipek P. A., Richelme C., Kennedy D. N., Caviness V. S., Jr The young adult human brain: an MRI-based morphometric analysis. Cereb Cortex. 1994 Jul-Aug;4(4):344–360. doi: 10.1093/cercor/4.4.344. [DOI] [PubMed] [Google Scholar]
  20. Fisher S. E., Vargha-Khadem F., Watkins K. E., Monaco A. P., Pembrey M. E. Localisation of a gene implicated in a severe speech and language disorder. Nat Genet. 1998 Feb;18(2):168–170. doi: 10.1038/ng0298-168. [DOI] [PubMed] [Google Scholar]
  21. Folstein S. E., Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet. 2001 Dec;2(12):943–955. doi: 10.1038/35103559. [DOI] [PubMed] [Google Scholar]
  22. Folstein S., Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry. 1977 Sep;18(4):297–321. doi: 10.1111/j.1469-7610.1977.tb00443.x. [DOI] [PubMed] [Google Scholar]
  23. Fombonne E., Bolton P., Prior J., Jordan H., Rutter M. A family study of autism: cognitive patterns and levels in parents and siblings. J Child Psychol Psychiatry. 1997 Sep;38(6):667–683. doi: 10.1111/j.1469-7610.1997.tb01694.x. [DOI] [PubMed] [Google Scholar]
  24. Fombonne E., Rogé B., Claverie J., Courty S., Frémolle J. Microcephaly and macrocephaly in autism. J Autism Dev Disord. 1999 Apr;29(2):113–119. doi: 10.1023/a:1023036509476. [DOI] [PubMed] [Google Scholar]
  25. Fombonne E. The epidemiology of autism: a review. Psychol Med. 1999 Jul;29(4):769–786. doi: 10.1017/s0033291799008508. [DOI] [PubMed] [Google Scholar]
  26. Frith U., Happé F. Autism: beyond "theory of mind". Cognition. 1994 Apr-Jun;50(1-3):115–132. doi: 10.1016/0010-0277(94)90024-8. [DOI] [PubMed] [Google Scholar]
  27. Gauger L. M., Lombardino L. J., Leonard C. M. Brain morphology in children with specific language impairment. J Speech Lang Hear Res. 1997 Dec;40(6):1272–1284. doi: 10.1044/jslhr.4006.1272. [DOI] [PubMed] [Google Scholar]
  28. Happé F. Autism: cognitive deficit or cognitive style? Trends Cogn Sci. 1999 Jun;3(6):216–222. doi: 10.1016/s1364-6613(99)01318-2. [DOI] [PubMed] [Google Scholar]
  29. Herbert Martha R., Harris Gordon J., Adrien Kristen T., Ziegler David A., Makris Nikos, Kennedy Dave N., Lange Nicholas T., Chabris Chris F., Bakardjiev Anna, Hodgson James. Abnormal asymmetry in language association cortex in autism. Ann Neurol. 2002 Nov;52(5):588–596. doi: 10.1002/ana.10349. [DOI] [PubMed] [Google Scholar]
  30. Jernigan T. L., Hesselink J. R., Sowell E., Tallal P. A. Cerebral structure on magnetic resonance imaging in language- and learning-impaired children. Arch Neurol. 1991 May;48(5):539–545. doi: 10.1001/archneur.1991.00530170103028. [DOI] [PubMed] [Google Scholar]
  31. Joseph Robert M., Tager-Flusberg Helen, Lord Catherine. Cognitive profiles and social-communicative functioning in children with autism spectrum disorder. J Child Psychol Psychiatry. 2002 Sep;43(6):807–821. doi: 10.1111/1469-7610.00092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kennedy D. N., Lange N., Makris N., Bates J., Meyer J., Caviness V. S., Jr Gyri of the human neocortex: an MRI-based analysis of volume and variance. Cereb Cortex. 1998 Jun;8(4):372–384. doi: 10.1093/cercor/8.4.372. [DOI] [PubMed] [Google Scholar]
  33. Kjelgaard Margaret M., Tager-Flusberg Helen. An Investigation of Language Impairment in Autism: Implications for Genetic Subgroups. Lang Cogn Process. 2001 Apr 1;16(2-3):287–308. doi: 10.1080/01690960042000058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lainhart J. E., Piven J., Wzorek M., Landa R., Santangelo S. L., Coon H., Folstein S. E. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):282–290. doi: 10.1097/00004583-199702000-00019. [DOI] [PubMed] [Google Scholar]
  35. Lamb J. A., Moore J., Bailey A., Monaco A. P. Autism: recent molecular genetic advances. Hum Mol Genet. 2000 Apr 12;9(6):861–868. doi: 10.1093/hmg/9.6.861. [DOI] [PubMed] [Google Scholar]
  36. Le Couteur A., Bailey A., Goode S., Pickles A., Robertson S., Gottesman I., Rutter M. A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry. 1996 Oct;37(7):785–801. doi: 10.1111/j.1469-7610.1996.tb01475.x. [DOI] [PubMed] [Google Scholar]
  37. Leboyer M., Bellivier F., Nosten-Bertrand M., Jouvent R., Pauls D., Mallet J. Psychiatric genetics: search for phenotypes. Trends Neurosci. 1998 Mar;21(3):102–105. doi: 10.1016/s0166-2236(97)01187-9. [DOI] [PubMed] [Google Scholar]
  38. Lincoln A. J., Courchesne E., Kilman B. A., Elmasian R., Allen M. A study of intellectual abilities in high-functioning people with autism. J Autism Dev Disord. 1988 Dec;18(4):505–524. doi: 10.1007/BF02211870. [DOI] [PubMed] [Google Scholar]
  39. Lord C., Risi S., Lambrecht L., Cook E. H., Jr, Leventhal B. L., DiLavore P. C., Pickles A., Rutter M. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000 Jun;30(3):205–223. [PubMed] [Google Scholar]
  40. Lord C., Rutter M., Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994 Oct;24(5):659–685. doi: 10.1007/BF02172145. [DOI] [PubMed] [Google Scholar]
  41. Mahoney W. J., Szatmari P., MacLean J. E., Bryson S. E., Bartolucci G., Walter S. D., Jones M. B., Zwaigenbaum L. Reliability and accuracy of differentiating pervasive developmental disorder subtypes. J Am Acad Child Adolesc Psychiatry. 1998 Mar;37(3):278–285. doi: 10.1097/00004583-199803000-00012. [DOI] [PubMed] [Google Scholar]
  42. Marchman V. A., Wulfeck B., Ellis Weismer S. Morphological productivity in children with normal language and SLI: a study of the English past tense. J Speech Lang Hear Res. 1999 Feb;42(1):206–219. doi: 10.1044/jslhr.4201.206. [DOI] [PubMed] [Google Scholar]
  43. Meaburn E., Dale P. S., Craig I. W., Plomin R. Language-impaired children: No sign of the FOXP2 mutation. Neuroreport. 2002 Jun 12;13(8):1075–1077. doi: 10.1097/00001756-200206120-00020. [DOI] [PubMed] [Google Scholar]
  44. Miles J. H., Hillman R. E. Value of a clinical morphology examination in autism. Am J Med Genet. 2000 Apr 10;91(4):245–253. [PubMed] [Google Scholar]
  45. Newbury D. F., Bonora E., Lamb J. A., Fisher S. E., Lai C. S. L., Baird G., Jannoun L., Slonims V., Stott C. M., Merricks M. J. FOXP2 is not a major susceptibility gene for autism or specific language impairment. Am J Hum Genet. 2002 Mar 13;70(5):1318–1327. doi: 10.1086/339931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Pickles A., Bolton P., Macdonald H., Bailey A., Le Couteur A., Sim C. H., Rutter M. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism. Am J Hum Genet. 1995 Sep;57(3):717–726. [PMC free article] [PubMed] [Google Scholar]
  47. Pinker S. Talk of genetics and vice versa. Nature. 2001 Oct 4;413(6855):465–466. doi: 10.1038/35097173. [DOI] [PubMed] [Google Scholar]
  48. Piven J., Arndt S., Bailey J., Andreasen N. Regional brain enlargement in autism: a magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 1996 Apr;35(4):530–536. doi: 10.1097/00004583-199604000-00020. [DOI] [PubMed] [Google Scholar]
  49. Piven J., Palmer P., Landa R., Santangelo S., Jacobi D., Childress D. Personality and language characteristics in parents from multiple-incidence autism families. Am J Med Genet. 1997 Jul 25;74(4):398–411. [PubMed] [Google Scholar]
  50. Plaisted K., O'Riordan M., Baron-Cohen S. Enhanced discrimination of novel, highly similar stimuli by adults with autism during a perceptual learning task. J Child Psychol Psychiatry. 1998 Jul;39(5):765–775. [PubMed] [Google Scholar]
  51. Plante E., Swisher L., Vance R., Rapcsak S. MRI findings in boys with specific language impairment. Brain Lang. 1991 Jul;41(1):52–66. doi: 10.1016/0093-934x(91)90110-m. [DOI] [PubMed] [Google Scholar]
  52. Prior M., Eisenmajer R., Leekam S., Wing L., Gould J., Ong B., Dowe D. Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders. J Child Psychol Psychiatry. 1998 Sep;39(6):893–902. [PubMed] [Google Scholar]
  53. Rapin I., Dunn M. Language disorders in children with autism. Semin Pediatr Neurol. 1997 Jun;4(2):86–92. doi: 10.1016/s1071-9091(97)80024-1. [DOI] [PubMed] [Google Scholar]
  54. Rapin I. Understanding childhood language disorders. Curr Opin Pediatr. 1998 Dec;10(6):561–566. doi: 10.1097/00008480-199810060-00004. [DOI] [PubMed] [Google Scholar]
  55. Rice M. L., Wexler K., Cleave P. L. Specific language impairment as a period of extended optional infinitive. J Speech Hear Res. 1995 Aug;38(4):850–863. doi: 10.1044/jshr.3804.850. [DOI] [PubMed] [Google Scholar]
  56. Rice M. L., Wexler K. Toward tense as a clinical marker of specific language impairment in English-speaking children. J Speech Hear Res. 1996 Dec;39(6):1239–1257. doi: 10.1044/jshr.3906.1239. [DOI] [PubMed] [Google Scholar]
  57. Risch N., Spiker D., Lotspeich L., Nouri N., Hinds D., Hallmayer J., Kalaydjieva L., McCague P., Dimiceli S., Pitts T. A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet. 1999 Aug;65(2):493–507. doi: 10.1086/302497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rosser E. M., Kaariainen H., Hurst J. A., Baraitser M., Hall C. M., Clayton P., Leonard J. V. Three patients with the osteochondrodysplasia and hypertrichosis syndrome--Cantu syndrome. Clin Dysmorphol. 1998 Apr;7(2):79–85. doi: 10.1097/00019605-199804000-00001. [DOI] [PubMed] [Google Scholar]
  59. Rutter M., Bailey A., Bolton P., Le Couteur A. Autism and known medical conditions: myth and substance. J Child Psychol Psychiatry. 1994 Feb;35(2):311–322. doi: 10.1111/j.1469-7610.1994.tb01164.x. [DOI] [PubMed] [Google Scholar]
  60. Rutter M. Genetic studies of autism: from the 1970s into the millennium. J Abnorm Child Psychol. 2000 Feb;28(1):3–14. doi: 10.1023/a:1005113900068. [DOI] [PubMed] [Google Scholar]
  61. Siegel D. J., Minshew N. J., Goldstein G. Wechsler IQ profiles in diagnosis of high-functioning autism. J Autism Dev Disord. 1996 Aug;26(4):389–406. doi: 10.1007/BF02172825. [DOI] [PubMed] [Google Scholar]
  62. Stevenson R. E., Schroer R. J., Skinner C., Fender D., Simensen R. J. Autism and macrocephaly. Lancet. 1997 Jun 14;349(9067):1744–1745. doi: 10.1016/S0140-6736(05)62956-X. [DOI] [PubMed] [Google Scholar]
  63. Szatmari P. Heterogeneity and the genetics of autism. J Psychiatry Neurosci. 1999 Mar;24(2):159–165. [PMC free article] [PubMed] [Google Scholar]
  64. Tager-Flusberg H. A psychological approach to understanding the social and language impairments in autism. Int Rev Psychiatry. 1999 Nov;11(4):325–334. doi: 10.1080/09540269974203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wassink Thomas H., Piven Joseph, Vieland Veronica J., Pietila Jennifer, Goedken Rhinda J., Folstein Susan E., Sheffield Val C. Evaluation of FOXP2 as an autism susceptibility gene. Am J Med Genet. 2002 Jul 8;114(5):566–569. doi: 10.1002/ajmg.10415. [DOI] [PubMed] [Google Scholar]
  66. Woodhouse W., Bailey A., Rutter M., Bolton P., Baird G., Le Couteur A. Head circumference in autism and other pervasive developmental disorders. J Child Psychol Psychiatry. 1996 Sep;37(6):665–671. doi: 10.1111/j.1469-7610.1996.tb01458.x. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES