medigraphic.com
ISSN 0185-3325 (Print)
Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2001, Number 3

<< Back Next >>

Salud Mental 2001; 24 (3)

Neurobiology of autism: An update

Weidenheim KM

Language: Spanish
References: 43
Page: 3-9
PDF size: 127.76 Kb.


ABSTRACT

Consideration of available studies suggests that many cases of autism are caused by a neurodevelopmental disorder. In other cases, a known disease entity is found, either during life or at autopsy. A common factor linking primary idiopathic autism with double syndrome cases having autistic behavior may be malfunction in specific neuroanatomic systems, defects in which give rise to the clinically defined autistic symptomatology. The available evidence suggests that the limbic system is abnormal in most cases of autism, and that the hippocampus, basal forebrain, cingulate and orbitofrontal cortices are specifically involved. Evidence for neocortical involvement is less strong; additional investigations will be necessary to define the role of neocortical pathology observed in some, but not all, individuals with autism. Similarly, the role of the thalamus and hypothalamus and their subdivisions needs to be better defined. The role of the cerebellum in the causation of autistic symptoms is controversial. However, the consistency of the findings of the Boston group suggest that additional study, especially studies focused on the connections of the cerebellum to the diencephalic and telencephalic structures, is warranted. The evidence, then, suggests that autism is a disorder of connectivity, often but not exclusively arising during the gestational period and ongoing degeneration of involved neural systems may occur in some individuals. Since different investigators, who study different populations of autistic individuals, have found involvement of multiple neuroanatomic sites, neural network(s) may be involved in pathogenesis of this complex behavior. A defect at any point in the network could produce autistic behavior, and differences in the specific network defect between individuals might account for observed differences in clinical phenotype. The recent identification of abnormalities in serotonin synthesis in autistic individuals suggests that serotonergic systems are likely involved (23). However, the complexity of the brain’s circuitry, especially in the limbic system (56), and the presence of multiple neurotransmitters in any given anatomic site in the brain, suggests that investigations of additional neurotransmitter systems might be useful as well. While autism is now accepted to be an intrinsic disorder of the brain, much additional work needs to be done to elucidate the precise biochemical and physiologic defects that lead to the observed pathologic changes. Application of basic neuroscience methods to clinical material will hopefully elucidate the pathogenesis of this disorder and lead to effective therapy.


REFERENCES

  1. AHLSEN G, ROSENGREN L, BELFRAGE M, PALM A, HAGLID K, HAMBERGER A, GILLBERG C: Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry, 33:734-743, 1993.

  2. AMERICAN PSYCHIATRIC ASSOCIATION: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, 1994.

  3. AMIR RE, VAN DEN VEYVER IB, WAN M, TRAN CQ,FRANCKE U, ZOGHBI HY: Rett Syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23:185-188, 2000.

  4. ARMSTRONG DD: Review of Rett Syndrome. J Neuropathol Exp Neurol, 56:843-849, 1997.

  5. ASPERGER H (translated by Frith, U): Autistic psychopathology in childhood. Reprinted in Frith U (ed). Autism and Asperger Syndrome. Cambridge University Press, 37-92, Cambridge, 1991.

  6. BACHEVALIER J, MERJANIAN PM: The contribution of medial temporal lobe structures in infantile autism: a neurobehavioral study in primates. In: Bauman ML, Kemper TL (eds). The Neurobiology of Autism. The Johns Hopkins University Press, 146-169, Baltimore, 1994.

  7. BAILEY A, LUTHERT P, BOLTON P, LE COUTEUR A, RUTTER M, HARDING B: Autism and megalencephaly. Lancet, 341:1225-1226, 1993.

  8. BAILEY A, LUTHERT P, DEAN A, HARDING B, JANOTA I, MONTGOMERY M, RUTTER M, LANTOS P: A clinicopathological study of autism. Brain, 121:889-905, 1998.

  9. BARON-COHEN S, RING HA, BULLMORE ET, WHEELWRIGHT S, ASHWIN C, WILLIAMS SC: The amygdala theory of autism. Neurosci Biobehav Rev, 24:355- 364, 2000.

  10. BAUMAN M, KEMPER TL: Histoanatomic observations of the brain in early infantile autism. Neurol, 35:866-874, 1985.

  11. BAUMAN ML, KEMPER TL: Abnormal cerebellar circuitry in autism? Neurol, 39 (Suppl 1):186, 1989.

  12. BAUMAN ML, KEMPER TL: Developmental cerebellar abnormalities: a consistent finding in early infantile autism. Neurol, 36 (Suppl 1):190, 1986.

  13. BAUMAN ML, KEMPER TL: Is autism a progressive process? Neurol, 48 (Suppl):A285, 1997.

  14. BAUMAN ML, KEMPER TL: Limbic and cerebellar abnormalities—consistent findings in infantile autism. J Neuropathol Exp Neurol, 47:369, 1988.

  15. BAUMAN ML, KEMPER TL: Limbic involvement in a second case of early infantile autism. Neurol, 37 (Suppl 1):147, 1987.

  16. BAUMAN ML, KEMPER TL: Neuroanatomic observations of the brain in autism. In: Bauman ML, Kemper TL (eds). The Neurobiology of Autism. The Johns Hopkins University Press, 119-145, Baltimore, 1994.

  17. BAUMAN ML, KEMPER TL: The brain in infantile autism: a histoanatomic case report. Neurol, 34 (Suppl 1):275, 1984.

  18. BAUMAN ML: Microscopic neuroanatomic abnormalities in autism. Pediatrics, 87 (Suppl):791-796, 1991.

  19. BERTHIER ML: Corticocallosal anomalies in Asperger’s syndrome. Am J Roentgenol, 162:236-237, 1994.

  20. BLUE ME, NAIDU S, JOHNSTON MV: Development of aminoacid receptors in frontal cortex from girls with Rett Syndrome. Ann Neurol, 45:541-545, 1999.

  21. BRYSON SE, CLARK BS, SMITH IM: First report of a Canadian epidemiological study of autistic syndromes. J Child Psychol Psychiatry, 29:433-445, 1988.

  22. CHEN RZ, AKBARIAN S, TUDOR M, JAENISCH R: Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nature Genetics, 27:327-31, 2001.0

  23. CHUGANI DC, MUZIK O, BEHEN M, ROTHERMEL R, JANISSE JJ, LEE J, CHUGANI HT: Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol, 45:287-295, 1999.

  24. COLEMAN PD, ROMANO J, LAPHAM L, SIMON W: Cell counts in cerebral cortex of an autistic patient. J Autism Dev Disorders, 15:245-255, 1985.

  25. COURCHESNE E, MULLER RA, SAITOH O: Brain weight in autism: normal in the majority of cases, megalencephalic in rare cases. Neurology, 52:1057-1059, 1999.

  26. COURCHESNE E, PRESS GA, YEUNG-COURCHESNE R: Parietal lobe abnormalities detected with MR in patients with infantile autism. Am J Roentgenol, 160:387-393, 1993.

  27. COURCHESNE E, TOWNSEND J, SAITOH O: The brain in infantile autism: posterior fossa structures are abnormal. Neurology, 44:214-223, 1997.

  28. DAMASIO AR, MAURER RG: A neurological model for childhood autism. Arch Neurol, 35:777-786, 1978.

  29. DARBY JH: Neuropathologic aspects of psychosis in childhood. J Autism Child Schiz, 6:339-352, 1976.

  30. EGAAS B, COURCHESNE E, SAITOH O: Reduced size of corpus callosum in autism. Arch Neurol, 52:794-801, 1995.

  31. FILIPEK PA: Quantitative MRI in autism: the cerebellar vermis. Current Opinion Neurol, 2:134-138, 1995.

  32. FOLSTEIN SE, PIVEN J: Etiology of autism: genetic influences. Pediatrics, 87 (Suppl):767-773, 1991.

  33. GAFFNEY GR, KUPERMAN S, TSAI LY, MINCHIN S: Morphological evidence for brainstem involvement in infantile autism. Biol Psychiatry, 24:578-586, 1988.

  34. GILCHRIST A, GREEN J, COX A, BURTON D, RUTTER M, LE COUTEUR A: Development and current functioning in adolescents with Asperger syndrome: a comparative study. J Child Psychol Psychiatry, 42:227-240, 2001.

  35. GILLBERG C: Subgroups in autism: are there behavioral0 0phenotypes typical of underlying medical conditions? J Intel Disabil Res, 36:201-214, 1992.

  36. GILLBERG C, COLEMAN M: The Biology of the Autistic Syndromes. The Lavenham Press Ltd, 3rd ed, Lavenham, 2000.

  37. GUERIN P, LYON G, BARTHELEMY C, SOSTAK E, CHEVROLLIER V, GARREAU B, LELORD G: Neuropathological study of a case of autistic syndrome with severe mental retardation. Develop Med Child Neurol, 38:203- 211, 1996.0

  38. GUY J, HENDRICH B, HOLMES M, MARTIN JE, BIRD A: A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nature Genetics, 27:322-326, 2001.

  39. HAGBERG B: Rett’s syndrome: prevalence and impact on progressive severe mental retardation in girls. Acta Paediatr Scand, 74:405, 1985.

  40. HASHIMOTO T, MURAKAWA K, MIYAZAKI M,TAYAMA M, KURODA Y: Magnetic resonance imaging of the brain structures in the posterior fossa in retarded autistic children. Acta Paediatr, 81:1030-1034, 1992.

  41. HASHIMOTO T, TAYAMA M, MIYAZAKI M, SAKURAMA N, YOSHIMOTO T, MURAKAWA K, KURODA Y: Reduced brainstem size in children with autism. Brain Dev, 14:94-97, 1992.

  42. HAZNEDAR M, BUCHSBAUM MS, WEI TC, HOF PR, CARTWRIGHT C, BIENSTOCK CA, HOLLANDER E: Limbic circuitry I patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry, 147:1994-2001, 2000.

  43. HEATH RG, DEMPSY CW, FONTANA CJ, MYERS WA: Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biol Psychiat, 13:501-529, 1978.




2020     |     www.medigraphic.com