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Gepubliceerd in: Journal of Autism and Developmental Disorders 12/2016

26-08-2016 | Brief Report

Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder

Auteurs: Ann Olincy, Audrey Blakeley-Smith, Lynn Johnson, William R. Kem, Robert Freedman

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 12/2016

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Abstract

Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor’s expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients’ attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect. Both patients perceived increased attention in their self-ratings. Alpha7-nicotinic receptor agonists, currently the target of drug development in schizophrenia and Alzheimer Disease, may also have positive clinical effects in autism spectrum disorder.
Literatuur
go back to reference Allen-Brady, K., Robison, R., Cannon, D., Varvil, T., Villalobos, M., et al. (2010). Genome-wide linkage in Utah autism pedigrees. Molecular Psychiatry, 15, 1006–1015.CrossRefPubMed Allen-Brady, K., Robison, R., Cannon, D., Varvil, T., Villalobos, M., et al. (2010). Genome-wide linkage in Utah autism pedigrees. Molecular Psychiatry, 15, 1006–1015.CrossRefPubMed
go back to reference Arnold, L. E., Aman, M. G., Holloway, J., Hurt, E., Bates, B., Xiaobai, L., et al. (2012). Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 22, 198–205.CrossRefPubMedPubMedCentral Arnold, L. E., Aman, M. G., Holloway, J., Hurt, E., Bates, B., Xiaobai, L., et al. (2012). Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 22, 198–205.CrossRefPubMedPubMedCentral
go back to reference Bacchelli, E., Battaglia, A., Cameil, C., Lomartire, S., Tancredi, R., Thomson, S., et al. (2015). Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. Amercian Journal of Medical Genetics Part A, 167A, 715–723.CrossRef Bacchelli, E., Battaglia, A., Cameil, C., Lomartire, S., Tancredi, R., Thomson, S., et al. (2015). Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. Amercian Journal of Medical Genetics Part A, 167A, 715–723.CrossRef
go back to reference Bejerot, S., & Nylander, L. (2003). Low prevalence of smoking in patients with autism spectrum disorders. Psychiatry Research, 119, 177–182.CrossRefPubMed Bejerot, S., & Nylander, L. (2003). Low prevalence of smoking in patients with autism spectrum disorders. Psychiatry Research, 119, 177–182.CrossRefPubMed
go back to reference Casey, J. P., Magalhaes, T., Conroy, J. M., Regan, R., Shah, N., Anney, R., et al. (2012). A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Human Genetics, 131, 565–579.CrossRefPubMed Casey, J. P., Magalhaes, T., Conroy, J. M., Regan, R., Shah, N., Anney, R., et al. (2012). A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Human Genetics, 131, 565–579.CrossRefPubMed
go back to reference Deutsch, S. L., Urbando, M. R., Neumann, S. A., Burket, J. A., & Katz, E. (2010). Cholinergic abnormalities in autism: Is there a rationale for selective nicotinic agonist interventions? Clinical Neuropharmacology, 33, 114–120.CrossRefPubMed Deutsch, S. L., Urbando, M. R., Neumann, S. A., Burket, J. A., & Katz, E. (2010). Cholinergic abnormalities in autism: Is there a rationale for selective nicotinic agonist interventions? Clinical Neuropharmacology, 33, 114–120.CrossRefPubMed
go back to reference Freedman, R. (2014). Alpha7-nicotinic receptor agonists for cognitive enhancement in schizophrenia. Annual Review of Medicine, 65, 245–256.CrossRefPubMed Freedman, R. (2014). Alpha7-nicotinic receptor agonists for cognitive enhancement in schizophrenia. Annual Review of Medicine, 65, 245–256.CrossRefPubMed
go back to reference Freedman, R., Coon, H., Myles-Worsley, M., Orr-Urtreger, A., Olincy, A., Davis, A., et al. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences, 94, 587–592.CrossRef Freedman, R., Coon, H., Myles-Worsley, M., Orr-Urtreger, A., Olincy, A., Davis, A., et al. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences, 94, 587–592.CrossRef
go back to reference Freedman, R., Olincy, A., Buchanan, R. W., Harris, J. G., Gold, J. M., Johnson, L., et al. (2008). Initial phase 2 trial of a nicotinic agonist in schizophrenia. American Journal of Psychiatry, 165, 1040–1047.CrossRefPubMedPubMedCentral Freedman, R., Olincy, A., Buchanan, R. W., Harris, J. G., Gold, J. M., Johnson, L., et al. (2008). Initial phase 2 trial of a nicotinic agonist in schizophrenia. American Journal of Psychiatry, 165, 1040–1047.CrossRefPubMedPubMedCentral
go back to reference Griffith, J., Hoffer, L. D., Adler, L. E., Zerbe, G. O., & Freedman, R. (1995). Effects of sound intensity on a midlatency evoked response to repeated auditory stimuli in schizophrenic and normal subjects. Psychophysiology, 32, 460–466.CrossRefPubMed Griffith, J., Hoffer, L. D., Adler, L. E., Zerbe, G. O., & Freedman, R. (1995). Effects of sound intensity on a midlatency evoked response to repeated auditory stimuli in schizophrenic and normal subjects. Psychophysiology, 32, 460–466.CrossRefPubMed
go back to reference Harris, J. G., Kongs, S., Allensworth, D. A., Sullivan, B., Zerbe, G., & Freedman, R. (2004). Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology, 29, 1378–1385.CrossRefPubMed Harris, J. G., Kongs, S., Allensworth, D. A., Sullivan, B., Zerbe, G., & Freedman, R. (2004). Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology, 29, 1378–1385.CrossRefPubMed
go back to reference Kemner, C., Oranje, B., Verbaten, M. N., & van Engeland, H. (2002). Normal P50 gating in children with autism. Journal of Clinical Psychiatry, 63, 214–217.CrossRefPubMed Kemner, C., Oranje, B., Verbaten, M. N., & van Engeland, H. (2002). Normal P50 gating in children with autism. Journal of Clinical Psychiatry, 63, 214–217.CrossRefPubMed
go back to reference Leonard, S., Gault, J., Hopkins, J., Logel, J., Vianzon, R., Short, M., et al. (2002). Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Archives of General Psychiatry, 59, 1085–1096.CrossRefPubMed Leonard, S., Gault, J., Hopkins, J., Logel, J., Vianzon, R., Short, M., et al. (2002). Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Archives of General Psychiatry, 59, 1085–1096.CrossRefPubMed
go back to reference Magnée, M. J. C. M., & Oranje, B. (2009). Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence for impaired brain connectivity? Neuropsychologia, 47, 1728–1732.CrossRefPubMed Magnée, M. J. C. M., & Oranje, B. (2009). Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence for impaired brain connectivity? Neuropsychologia, 47, 1728–1732.CrossRefPubMed
go back to reference Mayes, S. D., & Dickerson, S. (2008). WISC-IV and WIAT-II in children with high-functioning autism. Journal of Autism and Developmental Disorders, 3, 428–439.CrossRef Mayes, S. D., & Dickerson, S. (2008). WISC-IV and WIAT-II in children with high-functioning autism. Journal of Autism and Developmental Disorders, 3, 428–439.CrossRef
go back to reference Mostafavi, M., Hardy, P., & Arnold, L. E. (2016). Varenicline in autism: theory and case report of clinical and biochemical changes. Journal of Child and Adolescent Psychopharmacology,. doi:10.1002/ajmg.a.37795.PubMed Mostafavi, M., Hardy, P., & Arnold, L. E. (2016). Varenicline in autism: theory and case report of clinical and biochemical changes. Journal of Child and Adolescent Psychopharmacology,. doi:10.​1002/​ajmg.​a.​37795.PubMed
go back to reference Newhouse, P., Kellar, K., Aisen, P., White, H., Wesnes, K., Coderre, E., et al. (2012). Nicotine treatment of mild cognitive impairment. Neurology, 78, 91–101.CrossRefPubMedPubMedCentral Newhouse, P., Kellar, K., Aisen, P., White, H., Wesnes, K., Coderre, E., et al. (2012). Nicotine treatment of mild cognitive impairment. Neurology, 78, 91–101.CrossRefPubMedPubMedCentral
go back to reference Olincy, A., Harris, J. G., Johnson, L., Pender, V., Kongs, S., Allensworth, D., et al. (2006). Proof-of-concept trial of an α7-nicotinic agonist in schizophrenia. Archives of General Psychiatry, 63, 630–638.CrossRefPubMed Olincy, A., Harris, J. G., Johnson, L., Pender, V., Kongs, S., Allensworth, D., et al. (2006). Proof-of-concept trial of an α7-nicotinic agonist in schizophrenia. Archives of General Psychiatry, 63, 630–638.CrossRefPubMed
go back to reference Orekhova, E. V., Stroganova, T. A., Prokofyev, A. O., Nygren, G., Gillberg, C., & Elam, M. (2008). Sensory gating in young children with autism: Relation to age, IQ, and EEG gamma oscillations. Neuroscience Letters, 434, 218–223.CrossRefPubMed Orekhova, E. V., Stroganova, T. A., Prokofyev, A. O., Nygren, G., Gillberg, C., & Elam, M. (2008). Sensory gating in young children with autism: Relation to age, IQ, and EEG gamma oscillations. Neuroscience Letters, 434, 218–223.CrossRefPubMed
go back to reference Piazza, C., Hanley, G. P., & Fisher, W. W. (1996). Functional analysis and treatment of cigarette pica. Journal of Applied Behavior Analysis, 29, 437–450.CrossRefPubMedPubMedCentral Piazza, C., Hanley, G. P., & Fisher, W. W. (1996). Functional analysis and treatment of cigarette pica. Journal of Applied Behavior Analysis, 29, 437–450.CrossRefPubMedPubMedCentral
go back to reference Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., & Regan, R. (2010). Functional impact of global rare copynumber variation in autism spectrum disorders. Nature, 466, 368–372.CrossRefPubMedPubMedCentral Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., & Regan, R. (2010). Functional impact of global rare copynumber variation in autism spectrum disorders. Nature, 466, 368–372.CrossRefPubMedPubMedCentral
go back to reference Ray, M. A., Graham, A. J., Lee, M., Perry, R. H., Court, J. A., & Perry, E. K. (2005). Neuronal nicotinic acetylcholine receptor subunits in autism: An immunohistochemical investigation in the thalamus. Neurobiology of Disease, 19, 366–377.CrossRefPubMed Ray, M. A., Graham, A. J., Lee, M., Perry, R. H., Court, J. A., & Perry, E. K. (2005). Neuronal nicotinic acetylcholine receptor subunits in autism: An immunohistochemical investigation in the thalamus. Neurobiology of Disease, 19, 366–377.CrossRefPubMed
go back to reference Souliéres, I., Dawson, M., Gernsbacher, M. A., & Mottron, L. (2011). The level and nature of autistic intelligence II: What about Asperger Syndrome? PLoS One, 6, e25372.CrossRefPubMedPubMedCentral Souliéres, I., Dawson, M., Gernsbacher, M. A., & Mottron, L. (2011). The level and nature of autistic intelligence II: What about Asperger Syndrome? PLoS One, 6, e25372.CrossRefPubMedPubMedCentral
go back to reference Spek, A. A., Scholte, E. M., & Van Berckelaer-Onnes, I. A. (2011). Local information processing in adults with high functioning autism and Asperger Syndrome: The usefulness of neuropsychological tests and self-reports. Journal of Autism and Developmental Disorders, 41, 859–869.CrossRefPubMed Spek, A. A., Scholte, E. M., & Van Berckelaer-Onnes, I. A. (2011). Local information processing in adults with high functioning autism and Asperger Syndrome: The usefulness of neuropsychological tests and self-reports. Journal of Autism and Developmental Disorders, 41, 859–869.CrossRefPubMed
go back to reference Stroganova, T. A., Kozunov, V. V., Posikera, I. N., Galuta, I. A., Gratchev, V. V., & Orekhova, E. V. (2013). Autism spectrum disorder contributes to their atypical auditory behavior: An ERP study. PLoS One, 8(e69100), 1–23. Stroganova, T. A., Kozunov, V. V., Posikera, I. N., Galuta, I. A., Gratchev, V. V., & Orekhova, E. V. (2013). Autism spectrum disorder contributes to their atypical auditory behavior: An ERP study. PLoS One, 8(e69100), 1–23.
go back to reference Turner, M. A. (1999). Generating novel ideas: Fluency performance in high-functioning and learning disabled individuals with autism. Journal of Child Psychology and Psychiatry, 40, 189–201.CrossRefPubMed Turner, M. A. (1999). Generating novel ideas: Fluency performance in high-functioning and learning disabled individuals with autism. Journal of Child Psychology and Psychiatry, 40, 189–201.CrossRefPubMed
go back to reference Van Schalkwyk, G. I., Lewis, A. S., Qayyum, Z., Koslosky, K., Picciotto, M. R., & Volkmar, F. R. (2015). Reduction of aggressive episodes after repeated transdermal nicotine administration in a hospitalized adolescent with autism spectrum disorder. Journal of Autism and Developmental Disorders, 45, 3061–3066.CrossRefPubMedPubMedCentral Van Schalkwyk, G. I., Lewis, A. S., Qayyum, Z., Koslosky, K., Picciotto, M. R., & Volkmar, F. R. (2015). Reduction of aggressive episodes after repeated transdermal nicotine administration in a hospitalized adolescent with autism spectrum disorder. Journal of Autism and Developmental Disorders, 45, 3061–3066.CrossRefPubMedPubMedCentral
go back to reference Yasui, D. H., Scoles, H. A., Shin-ichi, H., Meguro-Horike, M., Dunaway, K. W., Schroeder, D. I., et al. (2011). 15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Human Molecular Genetics, 20, 4311–4323.CrossRefPubMedPubMedCentral Yasui, D. H., Scoles, H. A., Shin-ichi, H., Meguro-Horike, M., Dunaway, K. W., Schroeder, D. I., et al. (2011). 15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Human Molecular Genetics, 20, 4311–4323.CrossRefPubMedPubMedCentral
go back to reference Yoran-Hegesh, R., Kertzman, S., Vishne, T., Weizman, A., & Kotler, M. (2009). Neuropsychological mechanisms of digit symbol substitution test impairment in Asperger disorder. Psychiatry Research, 166, 35–45.CrossRefPubMed Yoran-Hegesh, R., Kertzman, S., Vishne, T., Weizman, A., & Kotler, M. (2009). Neuropsychological mechanisms of digit symbol substitution test impairment in Asperger disorder. Psychiatry Research, 166, 35–45.CrossRefPubMed
Metagegevens
Titel
Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder
Auteurs
Ann Olincy
Audrey Blakeley-Smith
Lynn Johnson
William R. Kem
Robert Freedman
Publicatiedatum
26-08-2016
Uitgeverij
Springer US
Gepubliceerd in
Journal of Autism and Developmental Disorders / Uitgave 12/2016
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI
https://doi.org/10.1007/s10803-016-2890-6

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