Skip to main content
    • Aa
    • Aa

Noradrenergic Moderation of Working Memory Impairments in Adults with Autism Spectrum Disorder

  • Kimberly E. Bodner (a1), David Q. Beversdorf (a1) (a2), Sanjida S. Saklayen (a3) and Shawn E. Christ (a1)

In addition to having difficulties with social communications, individuals with an autism spectrum disorder (ASD) often also experience impairment in higher-order, executive skills. The present study examined the effects of pharmacological modulation of the norepinephrine system on the severity of such impairments. A sample of 14 high-functioning adults with ASD and a demographically-matched comparison group of 13 typically developing individuals participated. An AX continuous performance test (AX-CPT) was used to evaluate working memory and inhibitory control. AX-CPT performance was assessed following administration of a single dose of propranolol (a beta adrenergic antagonist) and following placebo (sugar pill) administration. Individuals with ASD performed more poorly than non-ASD individuals in the working memory condition (BX trials). Importantly, administration of propranolol attenuated this impairment, with the ASD group performing significantly better in the propranolol condition than the placebo condition. Working memory performance of the non-ASD group was unaffected by propranolol/placebo administration. No group or medication effects were observed for the inhibition condition (AY trials). The present findings suggest that norepinephrine may play a role in some, but not necessarily all, cognitive impairments associated with ASD. Additional research is needed to fully understand whether this role is primarily causal or compensatory in nature. (JINS, 2012, 18, 556–564)

Corresponding author
Correspondence and reprint requests to: Shawn E. Christ, Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65203. E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

N. Adleman , V. Menon , C. Blasey , C. White , I. Warsofsky , G. Glover , A. Reiss (2002). A developmental fMRI study of the Stroop color-word task. Neuroimage, 16, 6175. doi:10.1006/nimg.2001.1046

J.K. Alexander , A. Hillier , R.M. Smith , M.E. Tivarus , D.Q. Beversdorf (2007). Beta-adrenergic modulation of cognitive flexibility during stress. Journal of Cognitive Neuroscience, 19, 468478. doi:10.1162/jocn.2007.19.3.468

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (Fourth Edition-Revised). Washington, DC: APA.

A.F. Arnsten (1998). Catecholamine modulation of prefrontal cortical cognitive function. Trends in Cognitive Sciences, 2, 436447. doi:10.1016/S1364-6613(98)01240-6

A.F. Arnsten , B.M. Li (2005). Neurobiology of executive functions: Catecholamine influences on prefrontal cortical functions. Biological Psychiatry, 57, 13771384. doi:10.1016/j.biopsych.2004.08.019

G. Aston-Jones , J. Rajkowski , J. Cohen (1999). Role of locus coeruleus in attention and behavioral flexibility. Biological Psychiatry, 46, 13091320. doi:10.1016/S0006-3223(99)00140-7

D.M. Barch , C.S. Carter , A.W. MacDonald , T.S. Braver , J.D. Cohen (2003). Context-processing deficits in schizophrenia: Diagnostic specificity, 4-week course, and relationships to clinical symptoms. Journal of Abnormal Psychology, 112, 132143. doi:10.1037/0021-843X.112.1.132

C. Barthelemy , N. Bruneau , J.M. Cottet-Eymard , J. Domenech-Jouve , B. Garreau , G. Lelord , L. Pyrin (1988). Urinary free and conjugated catecholamines and metabolites in autistic children. Journal of Autism and Developmental Disorders, 18, 583591. doi:10.1007/BF02211876

C.W. Berridge , B.D. Waterhouse (2003). The locus coeruleus-noradrenergic system: Modulation of behavioral state and state-dependent cognitive processes. Brain Research Reviews, 42, 3384. doi:10.1016 /S0165-0173(03)00143-7

D.Q. Beversdorf , A.L. Carpenter , R.F. Miller , J.S. Cios , A. Hillier (2008). Effect of propranolol on verbal problem solving in autism spectrum disorder. Neurocase, 14, 378. doi:10.1080/13554790802368661

B. Buchsbaum , S. Greer , W. Chang , K. Berman (2005). Meta-analysis of neuroimaging studies of the Wisconsin Card-Sorting Task and component processes. Human Brain Mapping, 25, 3545. doi:10.1002/hbm.20128

H.L. Campbell , M.E. Tivarus , A. Hillier , D.Q. Beversdorf (2008). Increased task difficulty results in greater impact of noradrenergic modulation of cognitive flexibility. Pharmacology Biochemistry and Behavior, 88, 222229. doi:10.1016/j.pbb.2007.08.003

S.E. Christ , D.D. Holt , D.A. White , L. Green (2007). Inhibitory control in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 37, 11551165. doi:10.1007/s10803-006-0259-y

S.E. Christ , L.E. Kester , K.E. Bodner , J.H. Miles (2011). Evidence for selective inhibitory impairment in individuals with autism spectrum disorder. Neuropsychology, 25, 690701. doi:10.1037/a0024256

D. Chugani , O. Muzik , R. Rothermel , M. Behen , P. Chakraborty , T. Mangner , H.T. Chugani (1997). Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Annals of Neurology, 42, 666669. doi:10.1111/j.1460-9568.1997.tb01635.x

J.T. Coull , C.D. Frith , R.J. Dolan , R.S. Frackowiak , P.M. Grasby (1997). The neural correlates of the noradrenergic modulation of human attention, arousal and learning. European Journal of Neuroscience, 9, 589598. doi:10.1111/j.1460-9568.1997.tb01635.x

J.T. Coull , H.C. Middleton , T.W. Robbins , B.J. Sahakian (1995a). Clonidine and diazepam have differential effects on tests of attention and learning. Psychopharmacology, 120, 322332. doi:10.1007/BF02311180

J.T. Coull , H.C. Middleton , T.W. Robbins , B.J. Sahakian (1995b). Contrasting effects of clonidine and diazepam on tests of working memory and planning. Psychopharmacology, 120, 311321. doi:10.1007/BF02311179

A.R. Damasio , R.G. Maurer (1978). A neurological model for childhood autism. Archives of Neurology, 35, 777786. doi:10.1001/archneur.1978.00500360001001

D. Dhossche , H. Applegate , A. Abraham , P. Maertens , L. Bland , A. Bencsath , J. Martinez (2002). Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: Stimulus for a GABA hypothesis of autism. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 8(8), PR1PR6. Retrieved from

E. Hill (2004). Executive dysfunction in autism. Trends in Cognitive Science, 8, 2632. doi:10.1016/j.tics.2003.11.003

P. Jäkälä , M. Riekkinen , J. Sirviö , E. Koivisto , K. Kejonen , M. Vanhanen , P. Riekkinen (1999). Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology, 20, 460470. doi:10.1016/S0893-133X(98)00127-4

C.A. Jaselskis , E.H. Cook Jr., K.E. Fletcher , B.L. Leventhal (1992). Clonidine treatment of hyperactive and impulsive children with autistic disorder. Journal of Clinical Psychopharmacology, 12, 322327. doi:10.1097/00004714-199210000-00005

R.M. Joseph , L.M. McGrath , H. Tager-Flusberg (2005). Executive dysfunction and its relation to language ability in verbal school-age children with autism. Developmental Neuropsychology, 27, 361378. doi:10.1207/s15326942dn2703_4

M.A. Just , V. Cherkassky , T. Keller , R.K. Kana , N.J. Minshew (2007). Functional and anatomical cortical underconnectivity in autism: Evidence from an fMRI study of an executive function task and corpus callosum morphometry. Cerebral Cortex, 17, 951961. doi:10.1093/cercor/bhl006

B.J. Kelley , K.R. Yeager , T.H. Pepper , D.Q. Beversdorf (2005). Cognitive impairment in acute cocaine withdrawal. Cognitive & Behavioral Neurology, 18, 108112. doi:10.1097/01.wnn.0000160823.61201.20

B.J. Kelley , K.R. Yeager , T.H. Pepper , R.A. Bornstein , D.Q. Beversdorf (2007). The effect of propranolol on cognitive flexibility and memory in acute cocaine withdrawal. Neurocase, 13, 320327. doi:10.1080/13554790701846148

L. Kenworthy , B. Yerys , L. Anthony , G. Wallace (2008). Understanding executive control in autism spectrum disorders in the lab and in the real world. Neuropsychology Review, 18, 320338. doi:10.1007/s11065-008-9077-7

H. Koshino , P.A. Carpenter , N.J. Minshew , V.L. Cherkassky , T.A. Keller , M.A. Just (2005). Functional connectivity in an fMRI working memory task in high-functioning autism. Neuroimage, 24, 810821. doi:10.1016/j.neuroimage.2004.09.028

H. Koshino , R.K. Kana , T.A. Keller , V.L. Cherkassky , N.J. Minshew , M.A. Just (2008). fMRI investigation of working memory for faces in autism: Visual coding and underconnectivity with frontal areas. Cerebral Cortex, 18, 289300. doi:10.1093/cercor/bhm054

C.R. Lake , M.G. Ziegler , D.L. Murphy (1977). Increased norepinephrine levels and decreased dopamine-beta-hydroxylase activity in primary autism. Archives of General Psychiatry, 34, 553556. doi:10.1001/archpsyc.1977.01770170063005

J. Levitt , R. Blanton , S. Smalley , P. Thompson , D. Guthrie , J. McCracken , A.W. Toga (2003). Cortical sulcal maps in autism. Cerebral Cortex, 13, 728735. doi:10.1093/cercor/13.7.728

C. Lord , M. Rutter , A. Le Couteur (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, 659685. doi:10.1007/BF02172145

M. Martchek , S. Thevarkunnel , M. Bauman , G. Blatt , T. Kemper (2006). Lack of evidence of neuropathology in the locus coeruleus in autism. Acta Neuropathologica, 111, 497499. doi:10.1007/s00401-006-0061-0

B. Milner , M. Petrides (1984). Behavioural effects of frontal-lobe lesions in man. Trends in Neurosciences, 7, 403407. doi:10.1016/S0166-2236(84)80143-5

R.B. Minderaa , G.M. Anderson , F.R. Volkmar , G.W. Akkerhuis , D.J. Cohen (1994). Noradrenergic and adrenergic functioning in autism. Biological Psychiatry, 36, 237241. doi:10.1016/0006-3223(94)90605-X

R. Muhle , S.V. Trentacoste , I. Rapin (2004). The genetics of autism. Pediatrics, 113, e472e486. doi:10.1542/peds.113.5.e472

S.M. Myers , C.P. Johnson (2007). Management of children with autism spectrum disorders. Pediatrics, 120, 11621182. doi:10.1542/peds.2007-2362

A. Narayanan , C.A. White , S. Saklayen , M.J. Scaduto , A.L. Carpenter , A. Abduljalil , D.Q. Beversdorf (2010). Effect of propranolol on functional connectivity in autism spectrum disorder: A pilot study. Brain Imaging and Behavior, 4, 189197. doi:10.1007/s11682-010-9098-8

T. Nickl-Jockschat , U. Habel , T. Maria Michel , J. Manning , A.R. Laird , P.T. Fox , S.B. Eickhoff (2011). Brain structure anomalies in autism spectrum disorder: A meta-analysis of VBM studies using anatomic likelihood estimation. Human Brain Mapping , doi:10.1002/hbm.21299 [Epub ahead of print]

T. Ohnishi , H. Matsuda , T. Hashimoto , T. Kunihiro , M. Nishikawa , T. Uema , M. Sasaki (2000). Abnormal regional blood flow in childhood autism. Brain, 123, 18381844. doi:10.1093/brain/123.9.1838

A. Owen , K. McMillan , A. Laird , E. Bullmore (2005). N-back working memory paradigm: A meta-analysis of normative functional neuroimaging studies. Human Brain Mapping, 25, 4659. doi:10.1002/hbm.20131

S. Ozonoff , D. Strayer , W.M. McMahon , F. Fillouz (1994). Executive function abilities in autism: An informational processing approach. Journal of Child Psychology & Psychiatry, 35, 10151031. doi:10.1111/j.1469-7610.1994.tb01807.x

B.F. Pennington , S. Ozonoff (1996). Executive functions and developmental psychopathology. Journal of Child Psychology & Psychiatry, 37, 5187. doi:10.1111/j.1469-7610.1996.tb01380.x

D.J. Posey , J.I. Puntney , T.M. Sasher , D.L. Kem , C.J. McDougle (2004). Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: A retrospective analysis of 80 cases. Journal of Child and Adolescent Psychopharmacology, 14, 233241. doi:10.1089/1044546041649084

A.E. Purcell , O.H. Jeon , A.W. Zimmerman , M.E. Blue , J. Pevsner (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology, 57, 16181628. Retrieved from

I. Rapin , R. Katzman (1998). Neurobiology of autism. Annals of Neurology, 43, 714. doi:10.1002/ana.410430106

J.J. Ratey , J. Bemporad , P. Sorgi , P. Bick , S. Polakoff , G. O'Driscoll , E. Mikkelsen (1987). Open trial effects of beta-blockers on speech and social behaviors in 8 autistic adults. Journal of Autism and Developmental Disorders, 17, 439446. doi:10.1007/BF01487073

C.A. Riccio , C.R. Reynolds , P. Lowe , J.J. Moore (2002). The continuous performance test: A window on the neural substrates for attention? Archives of Clinical Neuropsychology, 17, 235272. doi:10.1016/S0887-6177(01)00111-1

H.E. Rosvold , A.F. Mirsky , I. Sarason , E.D. Bransome , L.H. Beck (1956). A continuous performance test of brain damage. Journal of Consulting Psychology, 20, 343350. doi:10.1037/h0043220

J. Russell (1997). Autism as an executive disorder. Oxford: Oxford University Press.

C.H. Salmond , M. de Haan , K.J. Friston , D.G. Gadian , F. Vargha-Khadem (2003). Investigating individual differences in brain abnormalities in autism. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 358(1430), 405413. doi:10.1098/rstb.2002.1210

T. Shallice (1982). Specific impairments of planning. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 298, 199209. doi:10.1098/rstb.1982.0082

S.D. Steele , N.J. Minshew , B. Luna , J.A. Sweeney (2007). Spatial working memory deficits in autism. Journal of Autism and Developmental Disorders, 37, 605612. doi:10.1007/s10803-006-0202-2

D.T. Stuss , D.F. Benson (1986). The frontal lobes. New York: Raven.

D.L. Williams , G. Goldstein , N.J. Minshew (2006). The profile of memory function in children with autism. Neuropsychology, 20, 2129. doi:10.1037/0894-4105.20.1.21

D.L. Williams , G. Goldstein , P.A. Carpenter , N.J. Minshew (2005). Verbal and spatial working memory in autism. Journal of Autism and Developmental Disorders, 35, 747756. doi:10.1007/s10803-005-0021-x

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *