, Volume 193, Issue 1, pp 137–150 | Cite as

The effects of alcohol on laboratory-measured impulsivity after l-Tryptophan depletion or loading

  • Donald M. DoughertyEmail author
  • Dawn M. Marsh
  • Charles W. Mathias
  • Michael A. Dawes
  • Don M. Bradley
  • Chris J. Morgan
  • Abdulla A.-B. Badawy
Original Investigation



Indirect evidence supports a link between serotonergic activity and individual differences in the behavioral response to alcohol, but few studies have experimentally demonstrated that an individual’s biological state can influence the sensitivity to alcohol-induced behaviors.


Our purpose was to temporarily modify serotonin synthesis in healthy individuals to determine how altered biological states may interact with alcohol administration to affect impulsive behavior.

Materials and methods

In a repeated-measures design, 18 normal controls consumed a 50-g l-tryptophan (Trp) depleting (ATD) or loading (ATL) amino-acid beverage that temporarily decreased or increased (respectively) serotonin synthesis before receiving either a moderate dose of alcohol (0.65 g/kg) or placebo. All participants completed three impulsivity testing sessions on each of the five experimental days. Session one was a baseline session. Session two included testing after ATD-only or ATL-only. Session three included: (1) placebo after ATL (ATL+PBO); (2) placebo after ATD (ATD+PBO); (3) alcohol after ATL (ATL+ALC); (4) alcohol after ATD (ATD+ALC); and (5) Alcohol-only conditions. Impulsivity was assessed using the Immediate Memory Task (Dougherty et al., Behav Res Methods Instrum Comput 34:391–398, 2002), a continuous performance test yielding commission errors that have been previously validated as a component of impulsive behavior.


Primary findings were that ATD-only increased impulsive responding compared to ATL-only, and ATD+ALC increased commission errors to levels higher than either the ATL+ALC or Alcohol-only conditions.


These findings demonstrate that reduced serotonin synthesis can produce increased impulsivity even among non-impulsive normal controls, and that the behavioral effects of alcohol are, in part, dependent on this biological state.


Serotonin l-tryptophan depletion Alcohol Impulsivity Humans 



We thank Lauren Kirschbaum, T. Dorina Papageorgiou, and David Trotter for assisting with data collection for this study. A preliminary account of part of this work was presented at the British Association for Psychopharmacology meeting (Dougherty et al. 2004). None of the authors have a financial relationship with the funding agency of this study. This study was approved and conducted in compliance with the University of Texas Health Science Center at Houston’s Institutional Review Board in accordance with the ethical standards of the 1964 Declaration of Helsinki and current laws in the United States. While the authors Dougherty, Marsh, and Mathias were affiliated with the University of Texas Health Science Center at Houston during the data collection for this study, they have since relocated to the Wake Forest University School of Medicine.


  1. Allen TJ, Moeller FG, Rhoades HR, Cherek DR (1998) Impulsivity and history of drug dependence. Drug Alcohol Depend 50:137–145PubMedCrossRefGoogle Scholar
  2. Asberg M, Traskman L, Thoren P (1976) 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictor. Arch Gen Psychiatry 33:1193–1197PubMedGoogle Scholar
  3. Asberg M, Nordstrom P, Traskman-Bendz L (1986) Cerebrospinal fluid studies in suicide: an overview. Ann N Y Acad Sci 487:243–255PubMedCrossRefGoogle Scholar
  4. Badawy AA-B (1998) Alcohol, aggression and serotonin: metabolic aspects. Alcohol Alcohol 33:66–72PubMedGoogle Scholar
  5. Badawy AA-B (2003) Alcohol and violence and the possible role of serotonin. Crim Behav Ment Health 13:31–44PubMedCrossRefGoogle Scholar
  6. Badawy AA, Morgan CJ, Lovett JW, Bradley DM, Thomas R (1995) Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression. Pharmacopsychiatry 28:93–97PubMedCrossRefGoogle Scholar
  7. Badawy AA-B, Morgan CJ, Llewelyn MB, Albuquerque, SRJ, Farmer A (2005) Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome. J Psychopharmacol 19:385–391PubMedCrossRefGoogle Scholar
  8. Ballenger JC, Goodwin FK, Major LF, Brown GL (1979) Alcohol and central serotonin metabolism in man. Arch Gen Psychiatry 36:224–227PubMedGoogle Scholar
  9. Banki CM (1981) Factors influencing monoamine metabolites and tryptophan in patients with alcohol dependence. J Neural Transm 50:89–101PubMedCrossRefGoogle Scholar
  10. Banki CM, Arato M (1983) Amine metabolites, neuroendocrine findings, and personality dimensions as correlates of suicidal behavior. Psychiatry Res 10:253–261PubMedCrossRefGoogle Scholar
  11. Barkley RA (1991) The ecological validity of laboratory and analogue assessment methods of ADHD symptoms. J Abnorm Child Psychol 19:149–178PubMedCrossRefGoogle Scholar
  12. Barratt ES, Patton JH (1983) Impulsivity: cognitive, behavioral and psychophysiological correlates. In: Zuckerman M (ed) Biological bases of sensation seeking, impulsivity, and anxiety. Lawrence Earlbaum Associates, Hillsdale, NJ, pp 77–121Google Scholar
  13. Beale IL, Matthew PJ, Oliver S, Cornballis MC (1987) Performance of disabled and normal readers on the Continuous Performance Test. J Abnorm Child Psychol 15:229–238PubMedCrossRefGoogle Scholar
  14. Benkelfat C, Ellenbogen MA, Dean P, Palmour RM, Young SN (1994) Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. Arch Gen Psychiatry 51:687–697PubMedGoogle Scholar
  15. Berney A, Sookman D, Leyton M, Young SN, Benkelfat C (2006) Lack of effects on core obsessive-compulsive symptoms of tryptophan depletion during symptom provocation in remitted obsessive-compulsive disorder patients. Biol Psychiatry 59:853–857PubMedCrossRefGoogle Scholar
  16. Bhatti T, Gillin JC, Seifritz E, Moore P, Clark C, Golshan S, Stahl S, Rapaport M, Kelsoe J (1998) Effects of a tryptophan-free amino acid drink challenge on normal human sleep electroencephalogram and mood. Biol Psychiatry 43:52–59PubMedCrossRefGoogle Scholar
  17. Biggio G, Fadda F, Fanni P, Tagliamonte A, Gessa GL (1974) Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci 14:1321–1329PubMedCrossRefGoogle Scholar
  18. Bjork JM, Dougherty DM, Moeller FG, Cherek DR, Swann AC (1999) The effects of tryptophan depletion and loading on laboratory aggression in men: time course and a food-restricted control. Psychopharmacology 142:24–30PubMedCrossRefGoogle Scholar
  19. Bjork JM, Dougherty DM, Moeller FG, Swann AC (2000) Differential behavioral effects of plasma tryptophan depletion and loading in aggressive and nonaggressive men. Neuropsychopharmacology 22:357–369PubMedCrossRefGoogle Scholar
  20. Booij L, van der Does AJ, Riedel WJ (2003) Monoamine depletion in psychiatric and healthy populations: review. Mol Psychiatry 88:951–973CrossRefGoogle Scholar
  21. Booij L, van der Does AJ, Haffmans PM, Riedel WJ (2005) Acute tryptophan depletion as a model of depressive relapse: behavioural specificity and ethical considerations. J Affect Disord 86:305–311PubMedCrossRefGoogle Scholar
  22. Borg S, Kvande H, Liljeberg P, Mossberg D, Valverius P (1985) 5-Hydroxyindoleacetic acid in cerebrospinal fluid in alcoholic patients under different clinical conditions. Alcohol 2:415–418PubMedCrossRefGoogle Scholar
  23. Brown GL, Ballanger JC, Minichiello MD, Goodwin FK (1979) Human aggression and its relationship to cerebrospinal fluid 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, and homovanillic acid. In: Sandler M (ed) Psychopharmacology of aggression. Raven, New York, pp 131–148Google Scholar
  24. Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK (1982) Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 139:741–746PubMedGoogle Scholar
  25. Buss AH, Perry M (1992) The Aggression Questionnaire. J Pers Soc Psychol 63:452–459PubMedCrossRefGoogle Scholar
  26. Cappiello A, Sernyak MJ, Malison RT, McDougle CJ, Heninger GR, Price LH (1997) Effects of acute tryptophan depletion in lithium-remitted manic patients: a pilot study. Biol Psychiatry 42:1076–1078PubMedCrossRefGoogle Scholar
  27. Carlsson A, Lindqvist M (1978) Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino acids in rat brain. Naunyn Schmiedebergs Arch Pharmacol 303:157–164PubMedCrossRefGoogle Scholar
  28. Carpenter LL, Anderson GA, Pelton GH, Gudin JA, Kirwin PDS, Price LH, Heninger GR, McDougal CJ (1998) Tryptophan depletion during continuous CSF sampling in healthy human subjects. Neuropsychopharmacology 19:26–35PubMedCrossRefGoogle Scholar
  29. Carver CS, Miller CJ (2006) Relations of serotonin function to personality: current views and a key methodological issue. Psychiatry Res 144:1–15PubMedCrossRefGoogle Scholar
  30. Chambers RA, Taylor JR, Potenza MN (2003) Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 160:1041–1052PubMedCrossRefGoogle Scholar
  31. Cherek DR, Moeller FG, Schnapp W, Dougherty DM (1997) Studies of violent and nonviolent male parolees: I. Laboratory and psychometric measurements of aggression. Biol Psychiatry 41:514–522PubMedCrossRefGoogle Scholar
  32. Cleare AJ, Bond AJ (1995) The effect of tryptophan depletion and enhancement on subjective and behavioral aggression in normal healthy male subjects. Psychopharmacology 118:72–81PubMedCrossRefGoogle Scholar
  33. Coccaro EF, Berman ME, Kavoussi RJ (1997) Assessment of life history of aggression: development and psychometric characteristics. Psychiatry Res 73:147–157PubMedCrossRefGoogle Scholar
  34. Cornblatt BA, Risch NJ, Faris G, Friedman D, Erlenmeyer-Kimling L (1988) The Continuous Performance Test: Identical Pairs Version (CPT-IP) I. New findings about sustained attention in normal families. Psychiatry Res 26:223–238PubMedCrossRefGoogle Scholar
  35. Crean J, Richards JB, deWit H (2002) Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism. Behav Brain Res 15:349–357CrossRefGoogle Scholar
  36. Curzon G (1979) Relationship between plasma, CSF and brain tryptophan. J Neural Transm 15(Suppl):81–92Google Scholar
  37. de Wit H, Crean J, Richards JB (2000) Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans. Behav Neurosci 114:830–837PubMedCrossRefGoogle Scholar
  38. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR (1990) Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47:411–418PubMedGoogle Scholar
  39. Dougherty DM, Marsh DM (2003) Immediate and Delayed Memory Tasks (IMT/DMT 2.0): a research tool for studying attention, memory, and impulsive behavior (Manual). Neurobehavioral Research Laboratory and Clinic, University of Texas Health Science Center at Houston, Houston, TexasGoogle Scholar
  40. Dougherty DM, Bjork JM, Bennett RH, Moeller FG (1999a) The effects of a cumulative alcohol dosing procedure on laboratory aggression in men and women. J Stud Alcohol 60:322–329PubMedGoogle Scholar
  41. Dougherty DM, Bjork JM, Marsh DM, Moeller FG (1999b) Influence of trait hostility on tryptophan depletion-induced laboratory aggression. Psychiatry Res 88:227–232PubMedCrossRefGoogle Scholar
  42. Dougherty DM, Moeller FG, Bjork JM, Marsh DM (1999c) Plasma l-tryptophan depletion and aggression. Adv Exp Med Biol 467:57–65PubMedGoogle Scholar
  43. Dougherty DM, Moeller FG, Bjork JM, Marsh DM (1999d) Plasma l-tryptophan depletion and aggression. In: Huether G, Kochen W, Simat TJ, Steinhart H (eds) Tryptophan, serotonin and melatonin: basic aspects and applications. Kluwer Academic/Plenum, New York, pp 57–65Google Scholar
  44. Dougherty DM, Moeller FG, Steinberg JL, Marsh DM, Hines SE, Bjork JM (1999e) Alcohol increases commission error rates for a continuous performance test. Alcohol Clin Exp Res 23:1342–1351PubMedGoogle Scholar
  45. Dougherty DM, Marsh DM, Moeller FG, Chokshi RV, Rosen VC (2000) The effects of moderate and high doses of alcohol on attention, impulsivity, discriminability, and response bias in immediate and delayed memory task performance. Alcohol Clin Exp Res 24:1702–1711PubMedCrossRefGoogle Scholar
  46. Dougherty DM, Marsh DM, Mathias CW (2002) Immediate and Delayed Memory Tasks: a computerized measure of memory, attention, and impulsivity. Behav Res Meth Instrum Comput 34:391–398Google Scholar
  47. Dougherty DM, Bjork JM, Harper RA, Marsh DM, Moeller FG, Mathias CW (2003a) Behavioral impulsivity paradigms: a comparison in hospitalized adolescents with disruptive behavior disorders. J Child Psychol Psychiatry 44:1145–1157PubMedCrossRefGoogle Scholar
  48. Dougherty DM, Bjork JM, Harper RA, Mathias CW, Moeller FG, Marsh DM (2003b) Validation of the Immediate and Delayed Memory Tasks in hospitalized adolescents with disruptive behavior disorders. Psychol Rec 53:509–532Google Scholar
  49. Dougherty DM, Marsh DM, Mathias CW, Morgan CJ, Bradley DM, Badawy AA-B (2004) Impulsive behaviour differences following combined alcohol and l-tryptophan depletion/loading manipulation. J Psychopharmacol 18(Suppl to No 3):A32Google Scholar
  50. Dougherty DM, Marsh DM, Mathias CW, Swann AC (2005a) Bipolar disorder and substance abuse: the conceptualization and role of impulsivity. Psychiatric Times 22:32–35Google Scholar
  51. Dougherty DM, Mathias CW, Marsh DM, Jagar AA (2005b) Laboratory behavioral measures of impulsivity. Behav Res Meth Instrum Comput 37:82–90Google Scholar
  52. Drummond PD (2005) Effect of tryptophan depletion on symptoms of motion sickness in migraineurs. Neurology 65:620–622PubMedCrossRefGoogle Scholar
  53. Dufour MC (1999) What is moderate drinking? Defining “drinks” and drinking levels. Alcohol Res Health 23:5–14PubMedGoogle Scholar
  54. Dykman RA, Ackerman PT, Oglesby DM (1979) Selective and sustained attention in hyperactive, learning-disabled and normal boys. J Nerv Ment Dis 167:288–297PubMedCrossRefGoogle Scholar
  55. Eckardt MJ, File SE, Gessa GL, Grant KA, Guerri C, Hoffman PL, Kalant H, Koob GF, Li TK, Tabakoff B (1998) Effects of moderate alcohol consumption on the central nervous system. Alcohol Clin Exp Res 22:998–1040PubMedCrossRefGoogle Scholar
  56. Erickson CK, Matchett JA (1975) Correlation of brain amine changes with ethanol-induced sleep time in mice. In: Gross MM (ed) Alcohol intoxication and withdrawal. Experimental studies II. Plenum, New York, pp 419–430Google Scholar
  57. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology 146:348–361PubMedCrossRefGoogle Scholar
  58. Feola TW, de Wit H, Richards JB (2000) Effects of d-amphetamine and alcohol on a measure of behavioral inhibition in rats. Behav Neurosci 114:838–848PubMedCrossRefGoogle Scholar
  59. Fernstrom JD (1983) Role of precursor availability in control of monoamine biosynthesis in brain. Physiol Rev 63:484–546PubMedGoogle Scholar
  60. Fernstrom JD, Wurtman RJ (1972) Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178:414–416PubMedCrossRefGoogle Scholar
  61. First MB, Gibbon M, Spitzer RL, Williams JBW, Benjamin L (1997) Structured clinical interview for DSM-IV Axis II Personality Disorders (SCID-II). Biometrics Research, New York State Psychiatric Institute, NYGoogle Scholar
  62. First MB, Spitzer RL, Gibbon M, Williams JBW (2001) Structured clinical interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute, NYGoogle Scholar
  63. Gessa GL, Biggio G, Fadda F, Corsini GU, Tagliamonte A (1974) Effect of the oral administration of tryptophan-free amino acid mixtures on serum tryptophan, brain tryptophan and serotonin metabolism. J Neurochem 22:869–870PubMedCrossRefGoogle Scholar
  64. Giancola PR (2002) Irritability, acute alcohol consumption and aggressive behavior in men and women. Drug Alcohol Depend 68:263–274PubMedCrossRefGoogle Scholar
  65. Guimarães APM, Zeni C, Polanczyk GV, Genro JP, Roman T, Rohde LA, Hutz MH (2006) Serotonin genes and attention deficit/hyperactivity disorder in a brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys. Am J Med Genet Part B, Sep 6; [Epub ahead of print]Google Scholar
  66. Halperin JM, Wolf LE, Pascualvaca D, Newcorn JH, Healey JM, O’Brien JD, Morganstein A, Young J (1988) Differential assessment of attention and impulsivity in children. J Am Acad Child Adolesc Psych 27:326–329CrossRefGoogle Scholar
  67. Halperin JM, Wolf LE, Greenblatt ER, Young G (1991) Subtype analysis of commission errors on the continuous performance test. Dev Neuropsychol 7:207–217CrossRefGoogle Scholar
  68. Higley JD (2001) Individual differences in alcohol-induced aggression: a nonhuman primate model. Alcohol Res Health 25:12–19PubMedGoogle Scholar
  69. Hindmarch I, Kerr JS, Sherwood N (1991) The effects of alcohol and other drugs on psychomotor performance and cognitive function. Alcohol 26:71–79Google Scholar
  70. Keppel G (1991) Design and analysis: a researcher’s handbook. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
  71. Kruesi MJ (1989) Cruelty to animals and CSF 5-HIAA (letter). Psychiatry Res 28:115–116PubMedCrossRefGoogle Scholar
  72. Kruesi MJ, Rapoport JL, Hamburger S, Hibbs E, Potter WZ, Lenane M, Brown GL (1990) Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescent. Arch Gen Psychiatry 47(5):419–426PubMedGoogle Scholar
  73. Kruesi MJ, Hibbs ED, Zahn TP, Keysor CS, Manburger SD, Bartko JJ, Rapoport JL (1992) A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures? Arch Gen Psychiatry 49(6):429–435PubMedGoogle Scholar
  74. LeMarquand DG, Pihl RO, Young SN, Tremblay RE, Seguin JR, Palmour RM, Benkelfat C (1998) Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males. Neuropsychopharmacology 19:333–341PubMedGoogle Scholar
  75. LeMarquand DG, Benkelfat C, Pihl RO, Palmour RM, Young SN (1999) Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism. Am J Psychiatry 156:1771–1779PubMedGoogle Scholar
  76. Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Faraone SV (2007) Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B Neuropsychiatr Genet 144(1):14–19Google Scholar
  77. Lidberg L, Tuck JR, Asberg M, Scalia-Tomba GP, Bertilsson L (1985) Homicide, suicide and CSF 5-HIAA. Acta Psychiatr Scand 71(3):230–236PubMedCrossRefGoogle Scholar
  78. Limson R, Goldman D, Roy A, Lamparski D, Ravitz B, Adinoff B, Linnoila M (1991) Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls. Arch Gen Psychiatry 48:437–441PubMedGoogle Scholar
  79. López-Ibor JJ Jr, Saiz-Ruiz J, de los Cobos JCP (1985) Biological correlations of suicide and aggressivity in major depressions (with melancholia): 5-hydroxyindoleacetic acid and cortisol in cerebral spinal fluid, dexamethasone suppression test and therapeutic response to 5-hydroxytryptophan. Neuropsychobiology 14:67–74PubMedCrossRefGoogle Scholar
  80. Marsh DM, Dougherty DM, Moeller FG, Swann AC, Spiga R (2002) Laboratory-measured aggressive behavior of women: acute tryptophan depletion and augmentation. Neuropsychopharmacology 26:660–671PubMedCrossRefGoogle Scholar
  81. Mathias CW, Dougherty DM, Marsh DM, Moeller FG, Hicks LR, Dasher K, Bar-Eli L (2002) Laboratory measures of impulsivity: a comparison of women with or without childhood aggression. Psychol Rec 52:289–303Google Scholar
  82. Menkes DB, Coates DC, Fawcett JP (1994) Acute tryptophan depletion aggravates premenstrual syndrome. J Affect Disord 32:37–44PubMedCrossRefGoogle Scholar
  83. Miller HE, Deakin JF, Anderson IM (2000) Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers. Br J Psychiatry 176:182–188PubMedCrossRefGoogle Scholar
  84. Moeller FG, Dougherty DM (2001) Antisocial personality disorder, alcohol and aggression. Alcohol Res Health 25:5–11PubMedGoogle Scholar
  85. Moja EA, Antinoro E, Cesa-Bianchi M, Gessa GL (1984) Increase in stage 4 sleep after ingestion of a tryptophan-free diet in humans. Pharmacol Res Commun 16:909–914PubMedCrossRefGoogle Scholar
  86. Moja EA, Restani P, Corsini E, Stacchezzini MC, Asserto R, Galli CL (1991) Cycloheximide blocks the fall of plasma and tissue tryptophan levels after tryptophan-free amino acid mixtures. Life Sci 49:1121–1128PubMedCrossRefGoogle Scholar
  87. Moss HB (1987) Serotonergic activity and disinhibitory psychopathy in alcoholism. Med Hypotheses 23:353–361PubMedCrossRefGoogle Scholar
  88. Mulvihill LE, Skilling TA, Vogel-Sprott M (1997) Alcohol and the ability to inhibit behavior in men and women. J Stud Alcohol 58:600–605PubMedGoogle Scholar
  89. Munafo MR, Hayward G, Harmer C (2006) Selective processing of social threat cues following acute tryptophan depletion. J Psychopharmacol 20:33–39PubMedCrossRefGoogle Scholar
  90. Murphy FC, Smith KA, Cowen PJ, Robbins TW, Sahakian BJ (2002) The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology 163:42–53PubMedCrossRefGoogle Scholar
  91. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M (1997) Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci USA 94:5308–5313PubMedCrossRefGoogle Scholar
  92. Oosterlaan J, Logan GD, Sergeant JA (1998) Response inhibition in AD/HD, CD, comorbid AD/HD+CD, anxious, and control children: a meta-analysis of studies with the stop task. J Child Psychol Psychiatry 39:411–425PubMedCrossRefGoogle Scholar
  93. Ortner CNM, MacDonald TK, Olmstead M (2003) Alcohol intoxication reduces impulsivity in the delay-discounting paradigm. Alcohol Alcohol 38:151–156PubMedGoogle Scholar
  94. O’Toole K, Abramowitz A, Morris R, Dulcan MK (1997) Effects of methylphenidate and nonverbal learning in children with attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psych 36:531–538CrossRefGoogle Scholar
  95. Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt Impulsiveness Scale. J Clin Psychol 51:768–774PubMedCrossRefGoogle Scholar
  96. Pihl RO, Young SN, Harden P, Plotnick S, Chamberlain B, Ervin FR (1995) Acute effect of altered tryptophan levels and alcohol on aggression in normal human males. Psychopharmacology 119:353–360PubMedCrossRefGoogle Scholar
  97. Reilly JG, McTavish SFB, Young AH (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. J Psychopharmacol 11:381–392PubMedCrossRefGoogle Scholar
  98. Richards JB, Zhang L, Mitchell SH, de Wit H (1999) Delay or probability discounting in a model of impulsive behavior: effect of alcohol. J Exp Anal Behav 71:121–143PubMedCrossRefGoogle Scholar
  99. Riedel WJ, Sobczak S, Schmitt JA (2003) Tryptophan modulation and cognition. Adv Exp Med Biol 527:207–213PubMedGoogle Scholar
  100. Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ, Robbins TW (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146:482–491PubMedCrossRefGoogle Scholar
  101. Roiser JP, Muller U, Clark L, Sahakian BJ (2006) The effects of acute tryptophan depletion and serotonin transporter polymorphism on emotional processing in memory and attention. Int J Neuropsychopharmacol August 8, pp 1–13 [Epub ahead of print]Google Scholar
  102. Rouanet H, Lepine D (1970) Comparison between treatments in a repeated-measurement design: ANOVA and multivariate methods. Br J Math Stat Psychol 23:147–163Google Scholar
  103. Roy A, Linnoila M (1989) CSF studies on alcoholism and related behaviors. Prog Neuro-psychopharmacol Biol Psychiatry 13:505–511CrossRefGoogle Scholar
  104. Rubinsztein JS, Rogers RD, Riedel WJ, Mehta MA, Robbins TW, Sahakian BJ (2001) Acute dietary tryptophan depletion impairs maintenance of “affective set” and delayed visual recognition in healthy volunteers. Psychopharmacology 154:319–326PubMedCrossRefGoogle Scholar
  105. Sharma RP, Shapiro LE, Kamath SK, Soll EA, Watanabe MD, Davis JM (1997) Acute dietary tryptophan depletion: effects on schizophrenic positive and negative symptoms. Neuropsychobiology 35:5–10PubMedCrossRefGoogle Scholar
  106. Smith SE, Pihl RO, Young SN, Ervin FR (1987) A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males. Psychopharmacology 91:451–457PubMedCrossRefGoogle Scholar
  107. Stancampiano R, Melis F, Sarias L, Cocco S, Cugusi C, Fadda F (1997) Acute administration of a tryptophan-free amino acid mixture decreases 5-HT release in rat hippocampus in vivo. Reg Integ Comparat Physiol 41:R991–R994Google Scholar
  108. Swann AC, Anderson J, Dougherty DM, Moeller FG (2001) Measurement of inter-episode impulsivity in bipolar disorder: a preliminary report. Psychiatry Res 101:195–197PubMedCrossRefGoogle Scholar
  109. Sykes DH, Douglas VI, Weiss G, Minde KK (1971) Attention in hyperactive children and the effect of methylphenidate (Ritalin). J Child Psychol Psychiatry 12:129–139PubMedCrossRefGoogle Scholar
  110. Sykes DH, Douglas VI, Morgenstern G (1973) Sustained attention in hyperactive children. J Child Psychol Psychiatry 14:213–220PubMedCrossRefGoogle Scholar
  111. Taylor SP (1967) Aggressive behavior and physiological arousal as a function of provocation and the tendency to inhibit aggression. J Person 35:297–310PubMedCrossRefGoogle Scholar
  112. Taylor SP (1983) Alcohol and human physical aggression. In: Gottheil E, Druley KA, Skoloday TE, Waxman HM (eds) Alcohol, drug abuse and aggression. Charles C Thomas, Springfield, IL, pp 280–291Google Scholar
  113. Thompson LL, Whitmore EA, Raymond KM, Crowley TJ (2006) Measuring impulsivity in adolescents with serious substance and conduct problems. Assessment 13:3–15PubMedCrossRefGoogle Scholar
  114. Virkkunen M, Kallio E, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M (1994a) Personality profiles and state aggressiveness in Finnish alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 51:28–33PubMedGoogle Scholar
  115. Virkkunen M, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M (1994b) CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 51:20–27PubMedGoogle Scholar
  116. Walderhaug E, Lunde H, Nordvik JE, Landrø NI, Refsum H, Magnusson A (2002) Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology 164:385–391PubMedCrossRefGoogle Scholar
  117. Weltzin TE, Fernstrom MH, Fernstrom JD, Neuberger SK, Kaye WH (1995) Acute tryptophan depletion and increased food intake and irritability in bulimia nervosa. Am J Psychiatry 152:1668–1671PubMedGoogle Scholar
  118. Williams WA, Shoaf SE, Hommer D, Rawlings R, Linnoila M (1999) Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers. J Neurochem 72:1641–1647PubMedCrossRefGoogle Scholar
  119. WIN, Weight-control Information Network (2006) Weight and waist measurement: Tools for adults. Accessed 1/31/07
  120. Wolfe BE, Metzger ED, Jimerson DC (1995) Comparison of the effects of amino acid mixture and placebo on plasma tryptophan to large neutral amino acid ratio. Life Sci 56:1395–1400PubMedCrossRefGoogle Scholar
  121. Young SN (1993) The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatry Neurosci 18:235–244PubMedGoogle Scholar
  122. Young SN, Gauthier S (1981) Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid, and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid. J Neurol Neurosurg Psychiatry 44:323–327PubMedCrossRefGoogle Scholar
  123. Young SN, Ervin FR (1984) Cerebrospinal fluid measurements suggest precursor availability and sex are involved in the control of biogenic amine metabolism in a primate. J Neurochem 42:1570–1573PubMedCrossRefGoogle Scholar
  124. Young SN, Leyton M (2002) The role of serotonin in human mood and social interaction: insight from altered tryptophan levels. Pharmacol Biochem Behav 71:857–865PubMedCrossRefGoogle Scholar
  125. Young SN, Smith SE, Pihl RO, Ervin FR (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology 87:173–177PubMedCrossRefGoogle Scholar
  126. Young SN, Ervin FR, Pihl RO, Finn P (1989) Biochemical aspects of tryptophan depletion in primates. Psychopharmacology 98:508–511PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Donald M. Dougherty
    • 1
    Email author
  • Dawn M. Marsh
    • 1
  • Charles W. Mathias
    • 1
  • Michael A. Dawes
    • 1
  • Don M. Bradley
    • 2
  • Chris J. Morgan
    • 3
  • Abdulla A.-B. Badawy
    • 4
  1. 1.Neurobehavioral Research Laboratory and Clinic, Department of Psychiatry and Behavioral MedicineWake Forest University Health SciencesWinston-SalemUSA
  2. 2.Department of Medical Biochemistry, College of MedicineCardiff UniversityCardiffUK
  3. 3.Department of Medical BiochemistryUniversity Hospital of WalesCardiffUK
  4. 4.The Cardiff School of Health SciencesUniversity of Wales Institute Cardiff (UWIC)CardiffUK

Personalised recommendations