The Effect of Chronic Methylphenidate on Executive Function and Working Memory in Drug-NaÃ¯ve Children with Attention-Deficit Disorder
Background: The main problem in ADHD patients is disinhibition, while ADD patients mostly suffer from slow cognitive speed. Although studies have shown that children with ADHD have deficits in executive function and working memory, and that acute use of Methylphenidate improves these functions, less study has been done on ADD patients.
Methods: A four weeks, experimental, clinical trial was conducted with MPH 1 mg/kg/dose. Participants were 20 children aged 6-11 years with diagnosis ADD. Neuropsychological performance was assessed with scales taken from the Cambridge Neuropsychological Test Automated Battery.
Results: Methylphenidate improved problems in some aspects of Stocking of Cambridge test including minimum moves, mean subsequent thinking time and in mean moves, between errors, strategy and total error aspects of Spatial Working Memory. It had no effect on Spatial Span and Intra/Extra Dimensional subscales.
Conclusions: Studies show that ADHD patients have defect on all executive and working memory tests and acute and not chronic use of Methylphenidate improves their performance. This different effect of chronic Methylphenidate on ADD and ADHD patients is another sign of different brain involvements in these two subgroups.Â
Keywords: Attention Deficit Hyperactivity Disorder, Attention Deficit Disorder, Methylphenidate, Executive Function, Working Memory
2 Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiat 2005;57 (5):e404.
3 Nigg JT, Blaskey LG, Huang-Pollock CL, Rappley MD. Neuropsychological executive functions and DSM-IV ADHD subtypes. J Am Acad Child Adolesc Psychiatry. 2002;41(1):59-66.
4 Barkley RA, DuPaul GJ, McMurray MB. Comprehensive evaluation of attention deficit disorder with and without hyperactivity as defined by research criteria. J Consult Clin Psychol. 1990;58:775â€“89.
5 Bauermeister JJ, Matos M, Reina G, Salas CC, Martinez JV, Cumba E, et al. Comparison of the DSM-IV combined and inattentive types of ADHD in a school-based sample of Latino/Hispanic children. J Child Psychol Psychiatry. 2005 46(2):66-79
6 Kordon A, Kahl KG, Wahl K. New understanding of attention-deficit disorders-beyond the age-at-onset criterion of DSM-IV. Eur Arch Psychiatry Clin Neurosci. 2006;256 Suppl 1:i47â€“54.
7 Welsh MC, Pennington BF, Groisser DB. A normative-developmental study of executive function: A window of prefrontal function in children. Developmental Neuropsychology. 1991;7(2):131-49.
8 Beitchman JH. Development of psychopathology: Nature and nurture. J Can Acad Child Adolesc Psychiatry. 2002;15(2):96-7.
9 Maruff P, Burns CB, Tyler P, Currie BJ, Currie J. Neurological and cognitive abnormalities associated with chronic petrol sniffing. Brain 1998 121 ( Pt 10):1903-17.
10 Rhodes SM, Coghill DR, Matthews K. Acute neuropsychological effects of methylphenidate in stimulant drug-naive boys with ADHD II--broader executive and non-executive domains. J Child Psychol Psychiatry. 2006;47(11):1184-94.
11. Douglas V. Cognitive control processes in Attention-Deficit/Hyperactivity Disorder. In: Quay H, Hogan A, editors. Handbook of Disruptive Behavior Disorders: Springer US; 1999. p. 105-38.
12. Kempton S, Vance A, Maruff P, Luk E, Costin J, Pantelis C. Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children. Psychol Med 1999 29(3):527â€“38.
13. Rhodes SM, Coghill DR, Matthews K. Neuropsychological functioning in stimulant-naive boys with hyperkinetic disorder. Psychol Med. 2005;35(8):1109 -20.
14. Rhodes SM, Coghill DR, Matthews K. Methylphenidate restores visual memory, but not working memory function in attention deficit- hyperkinetic disorder. Psychopharmacology (Berl). 2004;175(3):319-30.
15 Chhabildas N, Pennington BF, Willcutt EG. A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD. J Abnorm Child Psychol. 2001 29(6):529â€“40.
16. Nigg JT. Is ADHD a disinhibitory disorder? . Psychol Bull. 2001;127(5):571-98.
17. Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW. Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci. 2000;20(6):Rc65.
18 Lou HC, Henriksen L, Bruhn P. Focal cerebral hypoperfusion in children with dysphasia and/or attention deficit disorder. Arch Neurol. 1984;41(8):825-9.
19 Lou HC, Henriksen L, Bruhn P, Borner H, Nielsen JB. Striatal dysfunction in attention deficit and hyperkinetic disorder. Arch Neurol. 1989 46(1):48-52.
20 Rapport MD, Denney CB, Chung KM, Hustace K. Internalizing behavior problems and scholastic achievement in children: Cognitive and behavioral pathways as mediators of outcome. J Clin Child Psychol. 2001;30(4):536-51.
21. Greenhill LL, Greenhill. Clinical effects of stimulant medication in ADHD. In: Solanto MN, Arnsten AFT, Castellanos FX, editors. Stimulant Drugs and ADHD. New York: Oxford University Press; 2001. p. 31â€“71.
22 Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, et al. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 2003;112(5):e404.
23. DeVito EE, Blackwell AD, Clark L, Kent L, Dezsery AM, Turner DC, et al. Methylphenidate improves response inhibition but not reflection-impulsivity in children with attention deficit hyperactivity disorder (ADHD). Psychopharmacology (Berl). 2008 202(1-3):531â€“9.
24. McBride PA, Anderson GM, Hertzig ME, Snow ME, Thompson SM, Khait VD, et al. Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psychiatry. 1998 37(7):737-76.
25. Garfinkel BD, Wender PH, Sloman L, O'Neill I. Tricyclic antidepressant and methylphenidate treatment of attention deficit disorder in children. J Am Acad Child Psychiatry. 1983; 22(4): 228-343.
26. Barkley RA. The inattentive type of ADHD as a distinct disorder: What remains to be done? . Clinical Psychology: Science and Practice. 2001;8:489â€“93.
27. Barkley RA, DuPaul GJ, McMurray MB. Attention deficit disorder with and without hyperactivity: Clinical response to three dose levels of methylphenidate. Pediatrics. 1991;87(4):519â€“31.
28. Milich R, Balentine AC, Lynam DR. ADHD combined type and ADHD predominantly inattentive type are distinct and unrelated disorders. Clinical Psychology: Science and Practice. 2001;8(4):463-88.
29. Weiss M, Worling D, Wasdell M. Chart review study of the inattentive and combined types of ADHD. J Atten Disord. 2003;7(1):1-9.
30 Luciana M, Nelson CA. The functional emergence of prefrontally-guided working memory systems in four-to-eight year old children. Neuropsychologia. 1998;36(3):273-93.
31 Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997b;121(1):65â€“ 94.
32 Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW. Effects of Methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl). 1997 131(2):196-206.
33 Coull JT, Middleton HC, Robbins TW, Sahakian BJ. Clonidine and diazepam have differential effects on tests of attention and learning. Psychopharmacology (Berl). 1995a 120(3):322â€“32.
34. Coull JT, Middleton HC, Robbins TW, Sahakian BJ. Contrasting effects of clonidine and diazepam on tests of working memory and Planning. Psychopharmacology (Berl). 1995b 120(3):311â€“21.
35. Jakala P, Riekkinen M, Sirvio J, Koivisto E, Kejonen K, Vanhanen M, et al. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology. 1999 20(5):460â€“70.
36 Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, et al. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: Implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology (Berl). 1999;146(4):482-91.
37 Goldberg MC, Mostofsky SH, Cutting LE, Mahone EM, Astor BC, Denckla MB, et al. Subtle executive impairment in children with autism and children with ADHD. J Autism Dev Disord. 2005 35(3):279-93.
38 Coghill DR, Rhodes SM, Matthews K. The Neuropsychological Effects of Chronic Methylphenidate on Drug-Naive Boys with Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry. 2007 62(9):954â€“62.
39. Mehta MA, Goodyer IM, Sahakian BJ. Methylphenidate improves working memory and set-shifting in AD/HD: relationships to baseline memory capacity. J Child Psychol Psychiatry. 2004;45(2):293-305.
40 Grodzinsky GM, Diamond R. Frontal lobe functioning in boys with ADHD. Developmental Neuropsychology. 1992;8(4):427-45.
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