The effects of alcohol on laboratory-measured impulsivity after l-Tryptophan depletion or loading
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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.
KeywordsSerotonin 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.
- 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
- 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
- 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
- Curzon G (1979) Relationship between plasma, CSF and brain tryptophan. J Neural Transm 15(Suppl):81–92Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- Dougherty DM, Mathias CW, Marsh DM, Jagar AA (2005b) Laboratory behavioral measures of impulsivity. Behav Res Meth Instrum Comput 37:82–90Google Scholar
- 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
- 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
- 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
- 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
- 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
- Keppel G (1991) Design and analysis: a researcher’s handbook. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- WIN, Weight-control Information Network (2006) Weight and waist measurement: Tools for adults. http://win.niddk.nih.gov/publications/tools.htm#bodymassindex. Accessed 1/31/07