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Journal of Autism and Developmental Disorders

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01-11-2014 | Brief Report

Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

Auteurs: Lawrence K. Fung, Robin A. Libove, Jennifer Phillips, Francois Haddad, Antonio Y. Hardan

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 11/2014

Abstract

The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.

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Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985). Psychometric characteristics of the aberrant behavior checklist. American Journal of Mental Deficiency, 89, 492–502.PubMed

APA. (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (4th ed.). Washington, DC: American Psychiatric Association.

Constantino, J. N., et al. (2003). Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 33, 427–433.PubMedCrossRef

Ebisch, S. J., et al. (2011). Altered intrinsic functional connectivity of anterior and posterior insula regions in high-functioning participants with autism spectrum disorder. Human Brain Mapping, 32, 1013–1028. doi:10.1002/hbm.21085.PubMedCrossRef

Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Rooney, R. J., Patel, D. H., & Thuras, P. D. (2010). mRNA and protein levels for GABAAalpha4, alpha5, beta1 and GABABR1 receptors are altered in brains from subjects with autism. Journal of Autism and Developmental Disorders, 40, 743–750. doi:10.1007/s10803-009-0924-z.PubMedCrossRefPubMedCentral

Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Rustan, O. G., Rooney, R. J., & Thuras, P. D. (2014). Downregulation of GABA receptor protein subunits alpha6, beta2, delta, epsilon, gamma2, theta, and rho2 in superior frontal cortex of subjects with autism. Journal of Autism and Developmental Disorders,. doi:10.1007/s10803-014-2078-x.PubMed

Fido, A., & Al-Saad, S. (2008). Olanzapine in the treatment of behavioral problems associated with autism: an open-label trial in Kuwait. Medical Principles and Practice, 17, 415–418. doi:10.1159/000141508.PubMedCrossRef

Gai, X., et al. (2012). Rare structural variation of synapse and neurotransmission genes in autism. Molecular Psychiatry, 17, 402–411. doi:10.1038/mp.2011.10.PubMedCrossRefPubMedCentral

Gogolla, N., Leblanc, J. J., Quast, K. B., Sudhof, T. C., Fagiolini, M., & Hensch, T. K. (2009). Common circuit defect of excitatory-inhibitory balance in mouse models of autism. Journal of Neurodevelopment Disorders, 1, 172–181. doi:10.1007/s11689-009-9023-x.CrossRef

Hosie, A. M., Wilkins, M. E., da Silva, H. M., & Smart, T. G. (2006). Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature, 444, 486–489.PubMedCrossRef

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., & Hudspeth, A. J. (2013). Principles of Neural Science (5th ed.). McGraw Hill Companies: New York.

Kemner, C., Willemsen-Swinkels, S. H., de Jonge, M., Tuynman-Qua, H., & van Engeland, H. (2002). Open-label study of olanzapine in children with pervasive developmental disorder. Journal of Clinical Psychopharmacology, 22, 455–460.PubMedCrossRef

Kostakis, E., et al. (2013). The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional N-methyl D-aspartate receptors to the cell surface via a noncanonical, G protein, and Ca2 + -dependent mechanism. Molecular Pharmacology, 84, 261–274. doi:10.1124/mol.113.085696.PubMedCrossRefPubMedCentral

Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.PubMedCrossRef

Lord, C., et al. (2000). The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.PubMedCrossRef

Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., & Paul, S. M. (1986). Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science, 232, 1004–1007.PubMedCrossRef

Marx, C. E., et al. (2009). Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology, 34, 1885–1903. doi:10.1038/npp.2009.26.PubMedCrossRefPubMedCentral

McDougle, C. J., et al. (1997). Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 685–693. doi:10.1097/00004583-199705000-00020.PubMedCrossRef

Mendez, M. A., et al. (2012). The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [(11)C]Ro15-4513 positron emission tomography study. Neuropharmacology,. doi:10.1016/j.neuropharm.2012.04.008.PubMed

Naylor, J., et al. (2010). Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction. Circulation Research, 106, 1507–1515. doi:10.1161/CIRCRESAHA.110.219329.PubMedCrossRefPubMedCentral

Oblak, A., Gibbs, T. T., & Blatt, G. J. (2009). Decreased GABA(A) receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Research, 2, 205–219. doi:10.1002/aur.88.PubMedCrossRefPubMedCentral

O’Roak, B. J., et al. (2011). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genetics, 43, 585–589. doi:10.1038/ng.835.PubMedCrossRefPubMedCentral

Osuji, I. J., Vera-Bolanos, E., Carmody, T. J., & Brown, E. S. (2010). Pregnenolone for cognition and mood in dual diagnosis patients. Psychiatry Research, 178, 309–312. doi:10.1016/j.psychres.2009.09.006.PubMedCrossRef

Ritsner, M. S., et al. (2010). Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. Journal of Clinical Psychiatry, 71, 1351–1362. doi:10.4088/JCP.09m05031yel.PubMedCrossRef

Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2, 255–267.CrossRef

Siever, L. J. (2008). Neurobiology of aggression and violence. American Journal of Psychiatry, 165, 429–442. doi:10.1176/appi.ajp.2008.07111774.PubMedCrossRefPubMedCentral

Solomon, M., et al. (2013). The development of the neural substrates of cognitive control in adolescents with autism spectrum disorders. Biological Psychiatry,. doi:10.1016/j.biopsych.2013.08.036.

Sparrow, S., Balla, D. A., & Cinchetti, D. (2005). Vineland Adaptive Behavior Scales. Bloomington: IN, Pearson Education Inc.

Sripada, R. K., Marx, C. E., King, A. P., Rampton, J. C., Ho, S. S., & Liberzon, I. (2013). Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biological Psychiatry, 73, 1045–1053. doi:10.1016/j.biopsych.2012.12.008.PubMedCrossRefPubMedCentral

Stigler, K. A., Mullett, J. E., Erickson, C. A., Posey, D. J., & McDougle, C. J. (2012). Paliperidone for irritability in adolescents and young adults with autistic disorder. Psychopharmacology (Berl), 223, 237–245. doi:10.1007/s00213-012-2711-3.CrossRef

Stigler, K. A., et al. (2009). Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 14-week, prospective, open-label study. Journal of Child and Adolescent Psychopharmacology, 19, 265–274. doi:10.1089/cap.2008.093.PubMedCrossRefPubMedCentral

Tomchek, S. D., & Dunn, W. (2007). Sensory processing in children with and without autism: a comparative study using the short sensory profile. The American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association, 61, 190–200.CrossRef

Titel: Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder
Auteurs: Lawrence K. Fung
Robin A. Libove
Jennifer Phillips
Francois Haddad
Antonio Y. Hardan
Publicatiedatum: 01-11-2014
Uitgeverij: Springer US
Gepubliceerd in: Journal of Autism and Developmental Disorders / Uitgave 11/2014
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI: https://doi.org/10.1007/s10803-014-2144-4

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