Reduced central nervous 5-HT neurotransmission in youth with ADHD influences ratings of a virtual opponents`extraversion a€“ Effects of trait-aggression

Abstract

Objective: Evidence from animal and human studies suggests that the neurobiology of aggressive behaviour and extraversion is linked with changes in serotonergic (5-HT) neurotransmission. The present study investigated the effects of diminished central nervous 5-HT neurotransmission following rapid tryptophan depletion (RTD) in youth diagnosed with attention deficit/hyperactivity disorder (ADHD). The study assessed the participants' opponent ratings after the experience of competing against a fictitious opponent in a competitive reaction time game (CRT) whilst under the influence of depletion/placebo. Method: 22 boys diagnosed with ADHD were subjected to a double-blind within-subject crossover-design, receiving RTD on one day, and on a further day a tryptophan balanced placebo. 4.5 hours after RTD/placebo intake they were subjected to provocation of aggressive behaviour using the CRT and asked to produce opponent ratings. Results: a€œLow aggressivea€ boys showed significantly higher extraversion ratings of their fictitious opponent compared to those of a€œhigh aggressivea€ boys under RTD versus placebo. Conclusion: The data support evidence that changes in 5-HT neurotransmission are involved in the neurobiological underpinnings of extraversion experienced by children and adolescents with ADHD. Future research with healthy controls and both genders is required to control for developmental and disorder-related effects.

Keywords

• Aggression; Serotonin; Rapid Tryptophan Depletion; ADHD; Opponent ratings

Kaynakça

1. Åsberg M, Träskman L, ThorenP. 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictor? Arch Gen Psychiatry 1976, 33:1193-1197.
2. Åsberg M, Schalling D, Träskman-Bendz L, Wagner A. Psychobiology of suicide, impulsivity and related phenomena. In MELTZER HY, eds. Psychopharmacology: third generation of progress, Raven Press, New York, Higley JD, Mehlmann PT, Poland RE et al. CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors. Biol Psychiatry 1996, 40: 1067
3. Mehlmann PT, Higley JD, Faucher L et al. Low CSF 5- HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry , 151: 1485-1491.
4. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC, American Psychiatric Press, 1994.
5. Herpertz-Dahlmann B, Konrad K, Herpertz SC. The Role of ADHD in the Etiology and Outcome of Antisocial Behavior and Psychopathy: In: Felthous AR, Sass H, eds. International Handbook on Psychopathic Disorders and the Law. (Bd. 1). John Wiley & Sons, England, 2007, 199–
6. Vloet TD, Herpertz S, Herpertz-Dahlmann B. Aetiology and life-course of conduct disorder in childhood: risk factors for the development of an antisocial personality disorder. Z Kinder Jugendpsychiatr Psychother. 2006, (2): 101-14.
7. Halperin JM, Sharma VSLJ, Schwartz ST, Matier K, Wornell G, Newcorn JH. Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder. Am J Psychiatry 1994, 151: 243
8. Halperin JM, Newcorn JH, Schwartz ST et al. Age- related changes in the association between serotonergic function and aggression in boys with ADHD. Biol Psychiatry 1997, 41: 682-689.

9. Pine DS, Coplan JD, Wasserman GA et al. Neuroendocrine response to fenfluramine challenge in boys. Arch Gen Psychiatry 1997; 54: 839-846.
10. Schulz KP, Newcorn JH, McKay KE et al. Relationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention- deficit/hyperactivity disorder. Psychiatry Res 2001, 101: 1
11. Stoff DM, Pasatiempo AP, Yeung JH, Cooper TB, Bridger WH, Rabinovich H. Neuroendocrine responses to challenge with D,L-fenfluramine and aggression in disruptive behavior disorders of children and adolescents. Psychiatry Res 1992, 43: 263-276.
12. Castellanos FX, Elia J, Kruesi MJet al. Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder. Psychiatry Res 1994, 52: 305-316.
13. Cohen DJ, Caparulo BK, Shaywitz BA, Bowers MB Jr. Dopamine neuropsychiatrically disturbed children. CSF homovanillic acid and 5-hydroxyindoleacetic acid. Arch Gen Psychiatry ; 34: 545-550. serotonin metabolism in Kruesi MJP, Rapoport JL, Hamburger S et al. Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Arch Gen Psychiatry 1990, 47: 426.
14. Kruesi MJP, Hibbs ED, Zahn TP et al. A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders: prediction by cerebrospinal homovanillic acid and autonomic measures? Arch Gen Psychiatry 1992, 49: 429-435. acid,
15. Shaywitz BA, Cohen DJ, Bowers MB Jr. CSF monoamine metabolites in children with minimal brain dysfunction: evidence for alteration of brain dopamine. A preliminary report. J Pediatr 1977, 90: 67-71.
16. Shetty T, Chase TN. Central monoamines and hyperkinase of childhood. Neurology 1976, 26: 1000
17. Stadler C, Schmeck K, Nowraty I, Müller WE, Poustka F. Platelet 5-HT uptake in boys with conduct disorder. Neuropsychobiology 2004, 50: 244-251.
18. Unis AS, Cook EH, Vincent JG et al. Platelet serotonin measures in adolescents with conduct disorder. Biol Psychiatry 1997, 42: 553-559.
19. LeMarquand DG, Pihl RO, Young SN et al. Tryptophan disinhibition Neuropsychopharmacology 1998, 19: 333-341. and males. in aggressive, adolescent
20. LeMarquand DG, Benkelfat C, Pihl RO, Palmour RM, Young SN. Behavioral disinhibition induced by tryptophan depletion multigenerational family histories of paternal alcoholism. Am J Psychiatry 1999, 156: 1771-1779. men with
21. Stadler C, Zepf FD, Demisch L, Schmitt M, Landgraf M, Poustka F. Influence of rapid tryptophan depletion on laboratory-provoked aggression in children with ADHD. Neuropsychobiology 2008, 56: 104-110.
22. Zepf FD, Stadler C, Demisch L, Schmitt M, Landgraf M, Poustka F. Serotonergic functioning and trait- impulsivity in attention-deficit/hyperactivity-disordered boys (ADHD): influence of rapid tryptophan depletion. Hum Psychopharmacol Clin Exp 2008, 23: 43-51.
23. Zepf FD, Holtmann M, Stadler C, Schmitt M, Poustka F. Diminished serotonergic functioning in hostile children with ADHD: Tryptophan Depletion increases behavioural inhibition. Pharmacopsychiatry 2008, 41: 60-65.
24. Zepf FD, Wöckel L, Poustka F, Holtmann M. Diminished 5-HT functioning in CBCL pediatric bipolar disorder profiled ADHD patients vs. normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance. Hum Psychopharmacol Clin Exp 2008, 23: 291-299.
25. Gessa GL, Biggio G, Fadda F, Corsini GU, Tagliamonte A. Effect of the oral administration of tryptophan-free amino acid mixtures on serum tryptophan, brain tryptophan and serotonin metabolism. J Neurochem ; 22: 869-870. Gessa GL, Biggio G, Fadda F, Corsini GU, Tagliamonte A. Tryptophan-free diet: a new means for rapidly decreasing brain tryptophan content and serotonin synthesis. Acta Vitaminol Enzymol 1975, 29: 72-78.
26. Moja EA, Stoff DM, Gessa GL, Castoldi D, Assereto R, Tofanetti O. Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man. Life Sci , 42: 1551-1556.
27. Biggio G, Fadda F, Fanni P, Tagliamonte A, Gessa GL. Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci 1974, 14: 1321-1329.
28. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 1990, 47: 411
29. Nishizawa S, Benkelfat C, Young SN et al. Differences in between males and females in rates of serotonin synthesis inhuman brain. Proc Natl Acad Sci U S A 1997, : 5308-5313.
30. Bjork JM, Dougherty DM, Moeller FG, Cherek DR, Swann AC. The effects of tryptophan depletion and loading on laboratory aggression in men: time course and a food-restricted control. Psychopharmacology (Berl) 1999, : 24-30.
31. Bjork JM, Dougherty DM, Moeller FG, Swann AC. Differential behavioral effects of plasma tryptophan depletion and loading in aggressive and nonaggressive men. Neuropsychopharmacology 2000, 22: 357-369.
32. Bond AJ, Wingrove J, Critchlow DG. Tryptophan depletion increases aggression in women during the premenstrual phase. Psychopharmacology (Berl) 2001, : 477-480.
33. Cleare AJ, Bond AJ. The effect of tryptophan depletion and enhancement on subjective and behavioural aggression in normal male subjects. Psychopharmacology 1995, 118: 81.
34. Dougherty DM, Bjork JM, Marsh DM, Moeller FG. Influence of trait hostility on tryptophan depletion-induced laboratory aggression. Psychiatry Res 2000, 88: 227-232.
35. Marsh DM, Dougherty DM, Moeller FG, Swann AC, Spiga R. Laboratory-measured aggressive behavior of women. Acute tryptophan depletion and augmentation. Neuropsychopharmacology 2002, 26: 660-671.
36. Moeller F, Dougherty D, Swann A, Collins D, Davis C, Cherek D. Tryptophan Depletion and aggressive responding in healthy males. Psychopharmacology 1996, : 97-113.
37. Pihl RO, Young SN, Harden P, Plotnick S, Chamberlain B, Ervin FR. Acute effect of altered tryptophan levels and alcohol on aggression in normal human males. Psychopharmacology 1995, 119: 353-360.
38. Salomon RM, Mazure CM, Delgado PL, Mendia P, Charney DS. Serotonin function in aggression: the effect of acute plasma trypophan depletion in aggressive patients. Biol Psychiatry 1994, 35: 570-572.
39. Walderhaug E, Lunde H, Nordvik JE, Landro NI, Refsum H, Magnusson A. Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology (Berl) 2002, 164: 385
40. Swanson JM, Volkow ND. Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD. Behav Brain Res 2002, 130: 73-78.
41. Demisch L, Kewitz A, Schmeck K et al. Methodology of rapid tryptophan depletion (RTD): impact of gender and body weight. Eur Arch Psychiatry Clin Neurosci 2002, 252 (Suppl. 2): I/25.
42. Pelham WE, Milich R, Cummings EM, Murphy DA, Schaughency EA, Greiner AR. Effects of background anger, provocation, and methylphenidate on emotional arousal and aggressive responding in attention-deficit hyperactivity disordered boys with and without concurrent aggressiveness. J Abnorm Child Psychol 1991, 19: 407
43. Bruning N. Entwicklung einer experimentellen Reaktionsprobe zur Erfassung von Aggression/Ärger bei 12jährigen. Unveröffentlichte Diplomarbeit. Johann Wolfgang Goethe Universität/Fachbereich Psychologie, Frankfurt am Main, 2000.
44. Buss AH, Perry M. The aggression questionnaire. Journal of Personality and Social Psychology 1992, 63: 459.
45. Hodapp V. Fragebogen zum Umgang mit anderen Personen Universität/Fachbereich Differentielle Psychologie und Psychologische Diagnostik, Frankfurt am Main, 2001. Wolfgang Goethe
46. Psychologie/Abteilung Eysenck SBG, Eysenck HJ. Impulsiveness and venturesomeness: their position in a dimensional system of personality description. Psychological Report 1978, 43: 1255.
47. Eysenck SBG, Eysenck HJ. Impulsiveness and venturesomeness in children. Pers Individ Dif 1980, 1: 73
48. Stadler C, Janke W. Concurrent validity of the German version of S.B. Eysenck´s impulsiveness questionnaire for children. Pers Individ Dif 2002, 35: 51-58.
49. Russo S, Kema IP, Bosker F, Haavik J, Korf J. Tryptophan as an evolutionary conserved signal to brain serotonin: implications. World J Biol Psychiatry 2007, 13: 1-11.
50. Epub ahead of print] evidence and psychiatric Flory JD, Newcorn JH, Miller C, Harty S, Halperin JM. Serotonergic function in children with attention deficit/hyperactivity disorder: relationship to later onset antisocial personality disorder. Br J Psychiatry 2007, 190: 414.
51. Kewitz A. Biochemische Untersuchungen zur Optimierung des »Rapid Tryptophan Depletion-Test« (RTD): Eine physiologische Methode zur akuten Vermidnerung der zentralnervösen Serotonin-Synthese in der Dissertationsarbeit, J. W. Goethe Universität, Frankfurt am Main, 2002. Forschung. Medizinische
52. Zepf FD, Poustka F. 5-HT functioning and aggression in children with ADHD and disruptive behavior disorders. Hum Psychopharmacol Clin Exp 2008, 23: 437-438.
53. Zepf FD, Wöckel L, Poustka F, Holtmann M. Dietary tryptophan depletion according to body weight - A new treatment option in acute mania? 2008. Medical Hypotheses 2009;72:47-48.
54. Marks DJ, Miller SR, Schulz KP, Newcorn JH, Halperin JM. The interaction of psychosocial adversity and biological risk in childhood aggression. Psychiatry Res , 151: 221-230. Zepf FD, Gaber TJ, Baurmann D, Bubenzer S, Konrad K, Herpertz-Dahlmann B, Stadler C, Poustka F, Wöckel L. Serotonergic neurotransmission and lapses of attention in children hyperactivity influences Neuropsychopharmacol 2010, 13: 933-941. deficit disorder: attentional tryptophan performance. Int J
55. Zepf FD, Holtmann M, Stadler C, Magnus S, Wöckel L, neurotransmission and mood self-ratings in children and adolescents with ADHD: no clear effect of rapid tryptophan Clinical and Experimental 2009, 24: 87-49- HT depletion. Human Psychopharmacology:
56. Zepf FD, Holtmann M, Stadler C, Wöckel L, Poustka F. Reduced serotonergic functioning changes heart rate in ADHD. Journal of Neural Transmission 2009, 116: 105