Advertisement

The Neurobiology of Attention-Deficit/Hyperactivity Disorder

  • Samuel R. Chamberlain
    Affiliations
    Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
    Search for articles by this author
  • Trevor W. Robbins
    Affiliations
    Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
    Search for articles by this author
  • Barbara J. Sahakian
    Affiliations
    Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
    Search for articles by this author
      This special issue of Biological Psychiatry focuses on attention-deficit/hyperactivity disorder (ADHD), a highly heritable and disabling condition characterized by core behavioral symptoms of impulsivity, hyperactivity, and/or inattention (
      American Psychiatric Association
      ). Attention-deficit/hyperactivity disorder is the most prevalent neuropsychiatric disorder of childhood with a prevalence of 4% to 10%. It is often overlooked that some 40% to 60% of these children will still show clinically significant symptoms into adulthood. Attention-deficit/hyperactivity disorder should not be seen as an absolute bar to academic and social success. However, it has been associated with educational difficulties, increased criminality, substance abuse, family breakups, and driving accidents. The excess cost of the condition (in terms of education, occupational impairment, and medical treatment) was estimated at $30 billion in the United States in 2000 (
      • Birnbaum H.G.
      • Kessler R.C.
      • Lowe S.W.
      • Secnik K.
      • Greenberg P.E.
      • Leong S.A.
      • et al.
      Costs of attention deficit-hyperactivity disorder (ADHD) in the US: Excess costs of persons with ADHD and their family members in 2000.
      ). Given the disabling and prevalent nature of ADHD, it is important to further our understanding of the neural underpinnings of this condition and the mechanisms by which drug treatments exert their beneficial effects.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed. American Psychiatric Press, Washington, DC1994
        • Birnbaum H.G.
        • Kessler R.C.
        • Lowe S.W.
        • Secnik K.
        • Greenberg P.E.
        • Leong S.A.
        • et al.
        Costs of attention deficit-hyperactivity disorder (ADHD) in the US: Excess costs of persons with ADHD and their family members in 2000.
        Curr Med Res Opin. 2005; 21: 195-206
        • Biederman J.
        Attention-deficit/hyperactivity disorder: A selective overview.
        Biol Psychiatry. 2005; 57: 1215-1220
        • Arnsten A.F.
        Fundamentals of attention-deficit/hyperactivity disorder: Circuits and pathways.
        J Clin Psychiatry. 2006; 67: 7-12
        • Arnsten A.F.
        Stimulants: Therapeutic actions in ADHD.
        Neuropsychopharmacology. 2006; 31: 2376-2383
        • Robbins T.W.
        Chemistry of the mind: Neurochemical modulation of prefrontal cortical function.
        J Comp Neurol. 2005; 493: 140-146
        • Wilens T.E.
        Mechanism of action of agents used in attention-deficit/hyperactivity disorder.
        J Clin Psychiatry. 2006; 67: 32-38
        • Volkow N.D.
        Stimulant medications: How to minimize their reinforcing effects?.
        Am J Psychiatry. 2006; 163: 359-361
        • Bymaster F.P.
        • Katner J.S.
        • Nelson D.L.
        • Hemrick-Luecke S.K.
        • Threlkeld P.G.
        • Heiligenstein J.H.
        • et al.
        Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder.
        Neuropsychopharmacology. 2002; 27: 699-711
        • Wee S.
        • Woolverton W.L.
        Evaluation of the reinforcing effects of atomoxetine in monkeys: Comparison to methylphenidate and desipramine.
        Drug Alcohol Depend. 2004; 75: 271-276
        • Robertson M.M.
        Attention deficit hyperactivity disorder, tics and Tourette’s syndrome: The relationship and treatment implications.
        Eur Child Adolesc Psychiatry. 2006; 15: 1-11
        • Sangal R.B.
        • Owens J.
        • Allen A.J.
        • Sutton V.
        • Schuh K.
        • Kelsey D.
        Effects of atomoxetine and methylphenidate on sleep in children with ADHD.
        Sleep. 2006; 29: 1573-1585
        • Greenhill L.L.
        • Biederman J.
        • Boellner S.W.
        • Rugino T.A.
        • Sangal R.B.
        • Earl C.Q.
        • et al.
        A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder.
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 503-511
        • Duteil J.
        • Rambert F.A.
        • Pessonnier J.
        • Hermant J.F.
        • Gombert R.
        • Assous E.
        Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals.
        Eur J Pharmacol. 1990; 180: 49-58
        • Boonstra A.M.
        • Kooij J.J.
        • Oosterlaan J.
        • Sergeant J.A.
        • Buitelaar J.K.
        Does methylphenidate improve inhibition and other cognitive abilities in adults with childhood-onset ADHD?.
        J Clin Exp Neuropsychol. 2005; 27: 278-298
        • Eagle D.M.
        • Tufft M.R.
        • Goodchild H.L.
        • Robbins T.W.
        • Buitelaar J.K.
        Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol.
        Psychopharmacology (Berl). 2007; 192: 193-206
        • Chamberlain S.R.
        • Muller U.
        • Blackwell A.D.
        • Clark L.
        • Robbins T.W.
        • Sahakian B.J.
        Neurochemical modulation of response inhibition and probabilistic learning in humans.
        Science. 2006; 311: 861-863
        • Turner D.C.
        • Robbins T.W.
        • Aron A.R.
        • Dowson J.
        • Sahakian B.J.
        Cognitive enhancing effects of modafinil in healthy volunteers.
        Psychopharmacology (Berl). 2003; 165: 260-269
        • Aron A.R.
        • Dowson J.H.
        • Blackwell A.D.
        • Sahakian B.J.
        • Robbins T.W.
        Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2003; 54: 1465-1468
        • Turner D.C.
        • Clark L.
        • Dowson J.
        • Robbins T.W.
        • Sahakian B.J.
        Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2004; 55: 1031-1040
        • Chamberlain S.R.
        • del Campo N.
        • Dowson J.
        • Muller U.
        • Clark L.
        • Robbins T.W.
        • et al.
        Response inhibition in adults with attention-deficit hyperactivity disorder was improved by a single oral dose of atomoxetine.
        Biol Psychiatry. 2007 (in press)
        • Chamberlain S.R.
        • Sahakian B.J.
        The neuropsychiatry of impulsivity.
        Curr Opin Psychiatry. 2007; 20: 255-261
        • Dlugos A.M.
        • Freitag C.
        • Hohoff C.
        • McDonald J.
        • Cook E.H.
        • Deckert J.
        • et al.
        Norepinephrine transporter gene variation modulates acute response to D-amphetamine.
        Biol Psychiatry. 2007; 61: 1296-1305
        • Durston S.
        A review of the biological bases of ADHD: What have we learned from imaging studies?.
        Ment Retard Dev Disabil Res Rev. 2003; 9: 184-195
        • Seidman L.J.
        • Valera E.M.
        • Makris N.
        Structural brain imaging of attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2005; 57: 1263-1272
        • Castellanos F.X.
        • Lee P.P.
        • Sharp W.
        • Jeffries N.O.
        • Greenstein D.K.
        • Clasen L.S.
        • et al.
        Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.
        JAMA. 2002; 288: 1740-1748
        • Seidman L.J.
        • Valera E.M.
        • Makris N.
        • Monuteaux M.C.
        • Boriel D.L.
        • Kelkar K.
        • et al.
        Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.
        Biol Psychiatry. 2006; 60: 1071-1080
        • Biederman J.
        • Mick E.
        • Faraone S.V.
        Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type.
        Am J Psychiatry. 2000; 157: 816-818
        • Aron A.R.
        • Fletcher P.C.
        • Bullmore E.T.
        • Sahakian B.J.
        • Robbins T.W.
        Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans.
        Nat Neurosci. 2003; 6: 115-116
        • Chambers C.D.
        • Bellgrove M.A.
        • Stokes M.G.
        • Henderson T.R.
        • Garavan H.
        • Robertson I.H.
        • et al.
        Executive “brake failure” following deactivation of human frontal lobe.
        J Cogn Neurosci. 2006; 18: 444-455