Psychopharmacology

, Volume 233, Issue 7, pp 1171–1178 | Cite as

Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study

  • Rachel M. Zamzow
  • Bradley J. Ferguson
  • Janine P. Stichter
  • Eric C. Porges
  • Alexandra S. Ragsdale
  • Morgan L. Lewis
  • David Q. Beversdorf
Original Investigation

Abstract

Rationale

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges.

Objectives

The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug’s effects.

Methods

In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration.

Results

Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response.

Conclusions

Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

Keywords

Autism Propranolol Conversational reciprocity Noradrenergic Autonomic Anxiety 

References

  1. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press, WashingtonGoogle Scholar
  2. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Press, WashingtonGoogle Scholar
  3. Bal E, Harden E, Lamb D, Van Hecke AV, Denver JW, Porges SW (2010) Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state. J Autism Dev Disord 40:358–370CrossRefPubMedGoogle Scholar
  4. Beck AT, Epstein N, Brown G, Steer RA (1988) An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56:893–897CrossRefPubMedGoogle Scholar
  5. Bellini S (2004) Social skill deficits and anxiety in high-functioning adolescents with autism spectrum disorders. Focus Autism Other Dev Stud 19:78–86CrossRefGoogle Scholar
  6. Berntson GG, Cacioppo JT, Quigley KS (1993) Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications. Psychophysiology 30:183–196CrossRefPubMedGoogle Scholar
  7. Beversdorf DQ, Carpenter AL, Miller RF, Cios JS, Hillier A (2008) Effect of propranolol on verbal problem solving in autism spectrum disorder. Neurocase 14:378–383CrossRefPubMedGoogle Scholar
  8. Beversdorf DQ, Saklayen S, Higgins KF, Bodner KE, Kanne SM, Christ SE (2011) Effect of propranolol on word fluency in autism. Cogn Behav Neurol 24:11–17CrossRefPubMedGoogle Scholar
  9. Bodner KE, Beversdorf DQ, Saklayen SS, Christ SE (2012) Noradrenergic moderation of working memory impairments in adults with autism spectrum disorder. J Int Neuropsychol Soc 18:556–564CrossRefPubMedGoogle Scholar
  10. Charney DS, Redmond D (1983) Neurobiological mechanisms in human anxiety evidence supporting central noradrenergic hyperactivity. Neuropharmacology 22:1531–1536CrossRefPubMedGoogle Scholar
  11. Cook EH, Leventhal BL, Heller W, Metz J, Wainwright M, Freedman DX (1990) Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine levels and intelligence. J Neuropsychiatry Clin Neurosci 2:268–274CrossRefPubMedGoogle Scholar
  12. Dadds M, MacDonald E, Cauchi A, Williams K, Levy F, Brennan J (2014) Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord 44:521–531CrossRefPubMedGoogle Scholar
  13. Damasio AR (1996) The somatic marker hypothesis and the possible functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci 351:1413–1420CrossRefPubMedGoogle Scholar
  14. Dawson ME, Schell AM, Filion DL (2007) The electrodermal system. In: Cacioppo JT, Tassinary LG, Berntson GG (eds) The handbook of psychophysiology, 3rd edn. Cambridge University Press, New York, pp 159–181Google Scholar
  15. Erickson C, Posey D, Stigler K, Mullett J, Katschke A, McDougle C (2007) A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 191:141–147CrossRefGoogle Scholar
  16. Erickson C, Veenstra-Vanderweele J, Melmed R, McCracken J, Ginsberg L, Sikich L et al (2014) STX209 (Arbaclofen) for autism spectrum disorders: an 8-week open-label study. J Autism Dev Disord 44:958–964CrossRefPubMedGoogle Scholar
  17. Faigel HC (1991) The effect of beta blockade on stress-induced cognitive dysfunction in adolescents. Clin Pediatr 30:441–445CrossRefGoogle Scholar
  18. Farmer C, Thurm A, Grant P (2013) Pharmacotherapy for the core symptoms in autistic disorder: current status of the research. Drugs 73:303–314CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gaus V (2011) Adult Asperger syndrome and the utility of cognitive-behavioral therapy. J Contemp Psychother 41:47–56CrossRefGoogle Scholar
  20. Geschwind DH (2009) Advances in autism. Annu Rev Med 60:367–380CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gillott A, Furniss F, Walter A (2001) Anxiety in high-functioning children with autism. Autism 5:277–286CrossRefPubMedGoogle Scholar
  22. Gillott A, Standen PJ (2007) Levels of anxiety and sources of stress in adults with autism. J Intellect Disabil 11:359–370CrossRefPubMedGoogle Scholar
  23. Guy L, Souders M, Bradstreet L, DeLussey C, Herrington J (2014) Brief report: emotion regulation and respiratory sinus arrhythmia in autism spectrum disorder. J Autism Dev Disord 44:2614–2620CrossRefPubMedGoogle Scholar
  24. Hasselmo ME, Linster C, Patil M, Ma D, Cekic M (1997) Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio. J Neurophysiol 77:3326–3339PubMedGoogle Scholar
  25. Hirstein W, Iversen P, Ramachandran VS (2001) Autonomic responses of autistic children to people and objects. Proc R Soc Lond B Biol 268:1883–1888CrossRefGoogle Scholar
  26. Heilman KJ, Bal E, Bazhenova OV, Sorokin Y, Perlman SB, Hanley MC et al (2008) Physiological responses to social and physical challenges in children: quantifying mechanisms supporting social engagement and mobilization behaviors. Dev Psychobiol 50:171–182CrossRefPubMedGoogle Scholar
  27. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L et al (2007) Oxytocin increases retention of social cognition in autism. Biol Psychiatry 61:498–503CrossRefPubMedGoogle Scholar
  28. Judd CM, Kenny DA, McClelland GH (2001) Estimating and testing mediation and moderation in within-subjects designs. Psychol Methods 6:115–134CrossRefPubMedGoogle Scholar
  29. Kerns CM, Maddox BB, Kendall PC, Rump K, Berry L, Schultz RT et al (2015) Brief measures of anxiety in non-treatment-seeking youth with autism spectrum disorder. Autism 19(8):969–979. doi:10.1177/1362361314558465 CrossRefPubMedGoogle Scholar
  30. Lader M (1988) β-adrenoceptor antagonists in neuropsychiatry: an update. J Clin Psychiatry 49:213–223PubMedGoogle Scholar
  31. Lake C, Ziegler MG, Murphy DL (1977) Increased norepinephrine levels and decreased dopamine-β-hydroxylase activity in primary autism. Arch Gen Psychiatry 34:553–556CrossRefPubMedGoogle Scholar
  32. Launay J, Bursztejn C, Ferrari P, Dreux C, Braconnier A, Zarifian E et al (1987) Catecholamines metabolism in infantile autism: a controlled study of 22 autistic children. J Autism Dev Disord 17:333–347CrossRefPubMedGoogle Scholar
  33. Lewis GF, Furman SA, McCool MF, Porges SW (2012) Statistical strategies to quantify respiratory sinus arrhythmia: are commonly used metrics equivalent? Biol Psychol 89:349–364CrossRefPubMedPubMedCentralGoogle Scholar
  34. Lord C, Rutter M, Couteur A (1994) Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24:659–685CrossRefPubMedGoogle Scholar
  35. Minderaa RB, Anderson GM, Volkmar FR, Akkerhuis GW, Cohen DJ (1994) Noradrenergic and adrenergic functioning in autism. Biol Psychiatry 36:237–241CrossRefPubMedGoogle Scholar
  36. Ming X, Julu PO, Brimacombe M, Connor S, Daniels ML (2005) Reduced cardiac parasympathetic activity in children with autism. Brain Dev 27:509–516CrossRefPubMedGoogle Scholar
  37. Montoya AK, Hayes AF (2015) Two condition within-participant statistical mediation analysis: a path-analytic framework., Under review Google Scholar
  38. Myers SM, Johnson CP (2007) Management of children with autism spectrum disorders. Pediatrics 120:1162–1182CrossRefPubMedGoogle Scholar
  39. Narayanan A, White C, Saklayen S, Scaduto M, Carpenter A, Abduljalil A et al (2010) Effect of propranolol on functional connectivity in autism spectrum disorder: a pilot study. Brain Imaging Behav 4:189–197CrossRefPubMedPubMedCentralGoogle Scholar
  40. Neuhaus E, Bernier R, Beauchaine T (2014) Brief report: social skills, internalizing and externalizing symptoms, and respiratory sinus arrhythmia in autism. J Autism Dev Disord 44:730–737CrossRefPubMedGoogle Scholar
  41. Patriquin MA, Scarpa A, Friedman BH, Porges SW (2013) Respiratory sinus arrhythmia: a marker for positive social functioning and receptive language skills in children with autism spectrum disorders. Dev Psychobiol 55:101–112CrossRefPubMedGoogle Scholar
  42. Pitzalis MV, Mastropasqua F, Massari F, Passantino A, Totaro P, Forleo C et al (1998) β-blocker effects on respiratory sinus arrhythmia and baroreflex gain in normal subjects. Chest 114:185–191CrossRefPubMedGoogle Scholar
  43. Porges SW (1985) Method and apparatus for evaluating rhythmic oscillations in aperiodic physiological response systems. Patent Number: 4,510,944. U.S. Patent Office, WashingtonGoogle Scholar
  44. Porges SW (1995) Cardiac vagal tone: a physiological index of stress. Neurosci Biobehav Rev 19:225–233CrossRefPubMedGoogle Scholar
  45. Porges SW (2005) The vagus: a mediator of behavioral and physiologic features. In: Bauman ML, Kemper TL (eds) The neurobiology of autism, 2nd edn. The Johns Hopkins University Press, Baltimore, pp 65–78Google Scholar
  46. Porges SW (2007) The polyvagal perspective. Biol Psychol 74:116–143CrossRefPubMedPubMedCentralGoogle Scholar
  47. Porges SW, Bohrer RE (1990) Analyses of periodic processes in psychophysiological research. In: Cacioppo JT, Tassinary LG (eds) Principles of psychophysiology: physical, social, and inferential elements. Cambridge University Press, New York, pp 708–753Google Scholar
  48. Ratey JJ, Bemporad J, Sorgi P, Bick P, Polakoff S, O’Driscoll G et al (1987) Brief report: open trial effects of beta-blockers on speech and social behaviors in 8 autistic adults. J Autism Dev Disord 17:439–446CrossRefPubMedGoogle Scholar
  49. Schaaf RC, Benevides TW, Leiby BE, Sendecki JA (2013) Autonomic dysregulation during sensory stimulation in children with autism spectrum disorder. J Autism Dev Disord 45:461–472CrossRefGoogle Scholar
  50. Spence SH (1998) A measure of anxiety symptoms among children. Behav Res Ther 36:545–566CrossRefPubMedGoogle Scholar
  51. Stichter JP, Herzog MJ, O’Connor KV, Schmidt C (2012) A preliminary examination of a general social outcome measure. Assess Eff Interv 38:40–52CrossRefGoogle Scholar
  52. Tordjman S, McBride PA, Hertzig ME, Snow ME, Anderson GM, Hall LM et al (1997) Plasma β-endorphin, adrenocorticotropin hormone, and cortisol in autism. J Child Psychol Psychiatry 38:705–715CrossRefPubMedGoogle Scholar
  53. Volkmar FR (2001) Pharmacological interventions in autism: theoretical and practical issues. J Clin Child Adolesc 30:80–87CrossRefGoogle Scholar
  54. Ward MM, Mefford IN, Parker SD, Chesney MA, Taylor CB, Keegan DL et al (1983) Epinephrine and norepinephrine responses in continuously collected human plasma to a series of stressors. Psychosom Med 45:471–486CrossRefPubMedGoogle Scholar
  55. Wechsler D (1999) Wechsler abbreviated scale of intelligence. The Psychological Coorporation, San AntonioGoogle Scholar
  56. Young NJ, Findling RL (2015) An update on pharmacotherapy for autism spectrum disorder in children and adolescents. Curr Opin Psychiatry 28:91–101Google Scholar
  57. Zamzow RM, Christ SE, Saklayen SS, Moffitt AJ, Bodner KE, Higgins KF et al (2014) Effect of propranolol on facial scanning in autism spectrum disorder: a preliminary investigation. J Clin Exp Neuropsychol 36:431–445CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Interdisciplinary Neuroscience Program, University of MissouriColumbiaUSA
  2. 2.Department of Special EducationUniversity of MissouriColumbiaUSA
  3. 3.Center for Cognitive Aging and Memory (CAM), Institute on Aging, McKnight Brain Institute, Department of Aging and Geriatric ResearchUniversity of FloridaGainesvilleUSA
  4. 4.Department of Biological SciencesUniversity of MissouriColumbiaUSA
  5. 5.Department of Psychological SciencesUniversity of MissouriColumbiaUSA
  6. 6.William and Nancy Thompson Endowed Chair in Radiology, Departments of Radiology and Neurology, and the Thompson Center for Autism and Neurodevelopmental DisordersUniversity of MissouriColumbiaUSA
  7. 7.Department of Radiology, DC069.10University of Missouri Health CareColumbiaUSA

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