Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-02T23:54:08.839Z Has data issue: false hasContentIssue false
  • English
  • Français

Autism Clinical Trials: Biological and Medical Issues in Patient Selection and Treatment Response

Published online by Cambridge University Press:  07 November 2014

George M. Anderson ,
Andrew W. Zimmerman ,
Natacha Akshoomoff  and
Diane C. Chugani
Get access Rights & Permissions [Opens in a new window]

Abstract

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.

Type
Review Article
Information
CNS Spectrums , Volume 9 , Issue 1 , January 2004 , pp. 57 - 64
Copyright
Copyright © Cambridge University Press 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.CAN Consensus Group. Autism screening and diagnostic evaluation: CAN consensus statement. CNS Spectr. 1998;3:40–49.CrossRefGoogle Scholar
2.Miles, JH, Hillman, RE. Value of a clinical morphology examination in autism. Am J Med Genet. 2000;91:245–253.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
3.Haas, RH, Townsend, J, Courchesne, E, et al.Neurologic abnormalities in infantile autism. J Child Neurol. 1996;11:84–92.CrossRefGoogle ScholarPubMed
4.Rapin, I. Appropriate investigations for clinical care versus research in children with autism. Brain Dev. 1999;21:152–156.CrossRefGoogle ScholarPubMed
5.Comi, AM, Zimmerman, AW, Frye, VH, et al.Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol. 1999;14:388–394.CrossRefGoogle ScholarPubMed
6.Filipek, PA, Accardo, PJ, Ashwal, S, et al.Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 2000;55:468–479.CrossRefGoogle Scholar
7.Wassink, TH, Piven, J, Patil, SR. Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet. 2001;11:57–63.CrossRefGoogle Scholar
8.Gillberg, C, Coleman, M. The Biology of the Autistic Syndromes. 3rd ed. London, England: MacKeith Press; 2000:262–268.Google Scholar
9.Tuchman, R. Treatment of seizure disorders and EEG abnormalities in children with autism spectrum disorders. J Autism Dev Disord. 2000;30:485–489.CrossRefGoogle ScholarPubMed
10.Giovanardi-Rossi, P, Posar, A, Parmeggiani, A. Epilepsy in adolescents and young adults with autistic disorder. Brain Dev. 2000;22:102–106.CrossRefGoogle Scholar
11.Shinnar, S, Rapin, I, Arnold, S, et al.Language regression in childhood. Pediatr Neurol. 2001;24:183–189.CrossRefGoogle ScholarPubMed
12.Hollander, E, Dolgoff-Kaspar, R, Cartwright, C, Rawitt, R, Novotny, S. An open trial of divalproex sodium in autism spectrum disorder. J Clin Psychiatry. 2001:62:530–534.CrossRefGoogle Scholar
13.Thirumalai, SS, Shubin, RA, Robinson, R. Rapid eye movement sleep behavior disorder in children with autism. J Child Neurol. 2002;17:173–178.CrossRefGoogle ScholarPubMed
14.Klin, A, Jones, W, Schultz, R, et al.Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism. Arch Gen Psychiatry. 2002;59:809–816.CrossRefGoogle ScholarPubMed
15.Bruneau, N, Roux, S, Adrien, J, Barthelemy, C. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave-T complex). Clin Neurophysiol. 1999;110:1927–1934.CrossRefGoogle ScholarPubMed
16.Boatman, D, Vining, EP, Freeman, J, Carson, B. Auditory processing studied prospectively in two hemidecortication patients. J Child Neurol. 2003;18:228–232.CrossRefGoogle Scholar
17.Ceponiene, R, Lepisto, T, Shestakova, A, et al.Speech sound-selective auditory impairment in infantile autism: can perceive but will not attend. Proc Natl Acad Sci USA. 2003;100:5567–5572.CrossRefGoogle Scholar
18.Hirstein, W, Iversen, P, Ramachandran, VS. Autonomic responses of autistic children to people and objects. Proc R Soc Lond B Biol Sci. 2001;268:1.CrossRefGoogle ScholarPubMed
19.Tordjman, S, Anderson, GM, McBride, PA, et al.Plasma B-endorphin, adrenocorticotropin hormone, and cortisol in autism. J Child Psychol Psychiatr. 1997;38:705–715.CrossRefGoogle ScholarPubMed
20.Belmonte, M, Cook, EH, Anderson, GM, et al.Directions for autism research and targets for therapy. Mol Psychiatry. In press.Google Scholar
21.Chugani, DC, Muzik, O, Behen, ME, et al.Developmental changes in brain serotonin synthesis capacity in autistic and non-autistic children. Ann Neurol. 1999;45:287–295.3.0.CO;2-9>CrossRefGoogle Scholar
22.Chugani, DC, Muzik, O. alpha-[C-11]Methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism.. J Cerebral Blood Flow Matab. 2000;20:2–9.CrossRefGoogle Scholar
23.Diksic, M, Young, SN. Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem. 2001;78:1185–1200.CrossRefGoogle ScholarPubMed
24.Shoaf, SE, Carson, RE, Hommer, D, et al., The suitability of 11 C-alpha-methyl-L-tryptophan as a tracer for serotonin synthesis. J Cerebral Blood Flow Matab. 2000;120:244–252.CrossRefGoogle Scholar
25.Chugani, DC, Muzik, O, Juhasz, C, et al.Postnatal maturation of human GABAA receptors measured with positron emission tomography. Ann Neurol. 2001;49:618–626.CrossRefGoogle ScholarPubMed
26.Pfund, Z, Chugani, DC, Behen, ME, et al.Abnormalities of GABAA receptors measured with [C-11]flumazenil PET in autistic children. Abstr Soc Neurosci. 2001;27:879.2.Google Scholar
27.Schultz, RT, Gauthier, I, Klin, A, et al.Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. Arch Gen Psychiatry. 2000;57:331–340.CrossRefGoogle ScholarPubMed
28.Pierce, K, Muller, RA, Ambrose, J, et al.Face processing occurs outside the fusiform ‘face area’ in autism: evidence from functional MRI. Brain. 200;124:2059–2073.Google Scholar
29.Courchesne, E, Karns, C, Davis, HR, et al.Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology. 2001;57:245–254.CrossRefGoogle ScholarPubMed
30.Courchesne, E, Saitoh, O, Yeung-Courchesne, R, et al.Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. Am J Roentgenol. 1994;162:123–130.CrossRefGoogle ScholarPubMed
31.Courchesne, E, Townsend, J, Saitoh, O. The brain in infantile autism: posterior fossa structures are abnormal. Neurology. 1994;44:214–223.CrossRefGoogle ScholarPubMed
32.Courchesne, E, Yeung-Courchesne, R, Press, GA, Hesselink, JR, Jernigan, TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318:1349–1354.CrossRefGoogle ScholarPubMed
33.Gaffney, GR, Tsai, LY, Kuperman, S, Minchin, S. Cerebellar structure in autism. Am J Dis Child. 1987;141:1330–1332.Google ScholarPubMed
34.Hashimoto, T, Tayama, M, Murakawa, K, et al.Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord. 1995;25:1–18.CrossRefGoogle ScholarPubMed
35.Levitt, J, Blanton, R, Capetillo-Cunliffe, L, Guthrie, D, Toga, A, McCracken, J. Cerebellar vermis lobules VIII-X in autism. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23:625–633.CrossRefGoogle ScholarPubMed
36.Murakami, JW, Courchesne, E, Press, GA, Yeung-Courchesne, R, Hesselink, JR. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol. 1989;46:689–694.CrossRefGoogle ScholarPubMed
37.Hardan, AY, Minshew, NJ, Harenski, K, Keshavan, MS. Poserior fossa magnetic resonance imaging in autism. J Am Acad Child Adolesc Psychiatry. 2001;40:666–672.CrossRefGoogle Scholar
38.Piven, J, Saliba, K, Bailey, J, Arndt, S. An MRI study of autism: the cerebellum revisited. Neurology. 1997;49:546–551.CrossRefGoogle ScholarPubMed
39.Egaas, B, Courchesne, E, Saitoh, O. Reduced size of corpus callosum in autism. Arch Neurol. 1995;52:794–801.CrossRefGoogle ScholarPubMed
40.Manes, F, Piven, J, Vrancic, D, Nanclares, V, Plebst, C, Starkstein, SE. An MRI study of the corpus callosum and cerebellum in mentally retarded autistic individuals. J Neuropsychiatry Clin Neurosci. 1999;11:470–474.CrossRefGoogle ScholarPubMed
41.Piven, J, Bailey, J, Ranson, BJ, Arndt, S. An MRI study of the corpus callosum in autism. Am J Psychiatry. 1997;154:1051–1055.Google ScholarPubMed
42.Haznedar, MM, Buchsbaum, MS, Wei, T-C, et al.Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonace imaging. Am J Psychiatry. 2000;157:1994–2001.CrossRefGoogle Scholar
43.Aylward, EH, Minshew, NJ, Field, K, Sparks, BF, Singh, N. Effect of age on brain volume and head circumference in autism. Neurology. 2002;59:175–183.CrossRefGoogle ScholarPubMed
44.Howard, M. Convergent neuroanatomic and behavioural evidence of an amygdala hypothesis of autism. Neuroreport. 2000;11:2931–2935.CrossRefGoogle ScholarPubMed
45.Pierce, K, Müller, RA, Ambrose, J, Allen, G, Courchesne, E. Face processing occurs outside the fusiform ‘face area’ in autism: evidence from functional MRI. Brain. 2001;124:2059–2073.CrossRefGoogle ScholarPubMed
46.Saitoh, O, Karns, C, Courchesne, E. Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism. Brain. 2001;124:1317–1324.CrossRefGoogle ScholarPubMed
47.Gaffney, GR, Kuperman, S, Tsai, LY, Minchin, S. Forebrain structure in infantile autism. J Am Acad Child Adolesc Psychiatry. 1989;28:534–537.CrossRefGoogle ScholarPubMed
48.Jacobson, R, Le Couteur, A, Howlin, P, Rutter, M. Selective subcortical abnormalities in autism. Psychol Med. 1988;18:39–48.CrossRefGoogle ScholarPubMed
49.Rosenbloom, S, Campbell, M, George, AE, et al.High resolution CT scanning in infantile autism: a quantitative approach. J Am Acad Child Psychiatry. 1984;23:72–77.CrossRefGoogle ScholarPubMed
50.Carper, RA, Moses, P, Tigue, ZD, Courchesne, E. Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage. 2002;16:1038–1051.CrossRefGoogle ScholarPubMed
51.Sparks, BF, Friedman, SD, Shaw, DW, et al.Brain structural abnormalities in young children with autism spectrum disorder. Neurology. 2002;59:184–192.CrossRefGoogle ScholarPubMed
52.Akshoomoff, N, Lord, C, Lincoln, AJ, et al.Outcome classification of preschoolers with autism spectrum disorders using MRI brain measures. J Am Acad Child Adolesc Psychiatry. In press.Google Scholar
53.Anderson, GM, Cohen, DJ. Neurochemistry of childhood psychiatric disorders. In: Lewis, M, ed. Child and Adolescent Psychiatry: A Comprehensive Textbook. 3rd ed. Baltimore, Md: Williams and Wilkins; 2002:47–60.Google Scholar
54.Cook, EH Jr.Brief report: pathophysiology of autism: neurochemistry. J Autism Dev Disord. 1996;26:221–225.CrossRefGoogle ScholarPubMed
55.Anderson, GM. Genetics of childhood disorders: XLV. Autism, Part 4: serotonin in autism. J Am Acad Child Adolesc Psychiatry. 2002;41:1513–1516.CrossRefGoogle ScholarPubMed
56.Martin, A, Koenig, K, Anderson, GM, Scahill, L. Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective, open-label study. J Autism Dev Disord. In press.Google Scholar
57.McBride, AP, Anderson, GM, Hertzig, ME, et al.Serotonergic responsivity in male young adults with autistic disorder. Arch Gen Psychiatry. 1989;46:213–221.CrossRefGoogle ScholarPubMed
58.Novotny, S, Hollander, E, Allen, A, et al.Increased growth hormone response to sumatriptan challenge in adult autistic disorders. Psychiatry Res. 2000;94:173–177.CrossRefGoogle ScholarPubMed
59.Storck, T, von Brevern, MC, Behrens, CK, Scheel, J, Bach, A. Transcriptomics in predictive toxicology. Curr Opin Drug Discov Devel. 2002;5:90–97.Google ScholarPubMed
60.Wasinger, VC, Corthals, GL. Proteomic tools for biomedicine. J Chromatogr. 2002:771:33–48.Google ScholarPubMed
61.Watkins, SM, German, JB. Toward the implementation of metabolomic assessments of human health and nutrition. Curr Opin Biotechnol. 2002;13:512–516.CrossRefGoogle ScholarPubMed
62.Oesterheld, JR, Flockhart, DA. Pharmacokinetics II: cytochrome P450-mediated drug interactions. In: Martin, A, Scahill, L, Charney, DS, Leckman, JF, eds. Pediatric Psychopharmacology. New York, NY: Oxford University Press; 2003:54–66.Google Scholar
63.Anderson, GM, Cook, EH. Pharmacogenetics: promise and potential in child and adolescent psychiatry. Child Adolesc Psychiatr Clin N Am. 2000;9:23–42.CrossRefGoogle ScholarPubMed
64.Veenstra-VanderWeele, J, Anderson, GM, Cook, EH Jr, Pharmacogenetics and the serotonin system: Initial studies and future directions. Eur J Pharmacol. 2001;410:165–181.CrossRefGoogle Scholar