Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism

This study investigated the effects of acute serotonin depletion on two measures of impulsive behavior in healthy men with a family history of alcoholism. Serotonin has been implicated in several forms of impulsive behavior, as well as in the etiology of Type II alcoholism. The present study was designed to determine if an acute disturbance of serotonin function would increase impulsive responding on two behavioral indices of impulsivity, and whether this effect would be greater in individuals with a genetic predisposition to alcoholism. Forty healthy men, half of whom had an alcoholic father, participated in a two-session study. Subjects ingested a tryptophan-depleting diet on one session and a balanced diet on the other session, and completed tasks measuring behavioral inhibition and delay discounting. Tryptophan depletion impaired performance on the behavioral inhibition task in the males with a positive family history, relative to the males without alcoholic relatives, whereas it improved behavioral inhibition in the family history negative group. Tryptophan depletion had negligible effects on mood, and it did not alter performance on the delay discounting task. The results provide partial support for the hypothesis that impulsive behavior is related to low serotonin function, and further suggests that the role of serotonin depends on genetic factors related to alcoholism. The results complement the results of a parallel study investigating the effects of serotonin depletion on a similar behavioral inhibition procedure in rats. Parallel studies in rats and humans are important to validate the large body of neurobiological research with non-human species to humans.

[1]  R. Tannock,et al.  Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[2]  H. de Wit,et al.  Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans. , 2000, Behavioral neuroscience.

[3]  W. Riedel,et al.  Specificity of the tryptophan depletion method , 1999, Psychopharmacology.

[4]  C. McDougle,et al.  Tryptophan Depletion During Continuous CSF Sampling in Healthy Human Subjects , 1998, Neuropsychopharmacology.

[5]  Gordon D. Logan,et al.  Effects of methylphenidate on inhibitory control in hyperactive children , 1989, Journal of abnormal child psychology.

[6]  H. de Wit,et al.  Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats , 1999, Psychopharmacology.

[7]  G. Logan,et al.  Inhibitory Control, Impulsiveness, and Attention Deficit Hyperactivity Disorder , 2022 .

[8]  G. Aghajanian,et al.  Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. , 1990, Archives of general psychiatry.

[9]  R. Salomon,et al.  Lack of behavioral effects of monoamine depletion in healthy subjects , 1997, Biological Psychiatry.

[10]  W. J. Riedel,et al.  Acute dietary tryptophan depletion impairs maintenance of "affective set" and delayed visual recognition in healthy volunteers , 2001, Psychopharmacology.

[11]  J. Turkkan,et al.  Alcohol and drug use by college males as a function of family alcoholism history. , 1990, Alcoholism, clinical and experimental research.

[12]  C. M. Bradshaw,et al.  Quantification of Steady-State Operant Behavior , 1982 .

[13]  B. Bergum,et al.  Attention and performance IX , 1982 .

[14]  C. Robert Cloninger,et al.  Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. , 1981, Archives of general psychiatry.

[15]  G. Ainslie Specious reward: a behavioral theory of impulsiveness and impulse control. , 1975, Psychological bulletin.

[16]  M. Vergnes,et al.  Tryptophan Deprivation: Effects on Mouse-killing and Reactivity in the Rat , 1981, Pharmacology Biochemistry and Behavior.

[17]  M Linnoila,et al.  Brain serotonin, type II alcoholism and impulsive violence. , 1993, Journal of studies on alcohol. Supplement.

[18]  M. Linnoila,et al.  Family history of alcoholism in violent offenders and impulsive fire setters. , 1989, Archives of general psychiatry.

[19]  R. Wurtman,et al.  Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids , 1972, Science.

[20]  M. Linnoila,et al.  A prospective follow-up study of alcoholic violent offenders and fire setters. , 1996, Archives of general psychiatry.

[21]  G. Logan,et al.  Are hyperactive children deficient in attentional capacity? , 1990, Journal of abnormal child psychology.

[22]  C. Benkelfat,et al.  Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism. , 1999, The American journal of psychiatry.

[23]  Camellia P. Clark,et al.  Clinical and Physiological Consequences of Rapid Tryptophan Depletion , 2000, Neuropsychopharmacology.

[24]  P. Soubrié Reconciling the role of central serotonin neurons in human and animal behavior , 1986, Behavioral and Brain Sciences.

[25]  R. Poland,et al.  CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors , 1996, Biological Psychiatry.

[26]  N. Petry Pathological gamblers, with and without substance use disorders, discount delayed rewards at high rates. , 2001, Journal of abnormal psychology.

[27]  R. Pihl,et al.  Tryptophan depletion causes a rapid lowering of mood in normal males , 2004, Psychopharmacology.

[28]  H. de Wit,et al.  Delay or probability discounting in a model of impulsive behavior: effect of alcohol. , 1999, Journal of the experimental analysis of behavior.

[29]  H. Huynh,et al.  Estimation of the Box Correction for Degrees of Freedom from Sample Data in Randomized Block and Split-Plot Designs , 1976 .

[30]  M. Schuckit,et al.  Platelet serotonin uptake in men with family histories of alcoholism. , 1991, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[31]  A. Logue Research on self-control: An integrating framework , 1988, Behavioral and Brain Sciences.

[32]  M. Selzer The Michigan alcoholism screening test: the quest for a new diagnostic instrument. , 1971, The American journal of psychiatry.

[33]  D M Parker,et al.  The Short NART: cross-validation, relationship to IQ and some practical considerations. , 1991, The British journal of clinical psychology.

[34]  Antoine Depaulis,et al.  Parachlorophenylalanine-induced serotonin depletion increases offensive but not defensive aggression in male rats , 1986, Physiology & Behavior.

[35]  J. E. Mazur An adjusting procedure for studying delayed reinforcement. , 1987 .

[36]  C. Benkelfat,et al.  Tryptophan Depletion, Executive Functions, and Disinhibition in Aggressive, Adolescent Males , 1998, Neuropsychopharmacology.

[37]  Ting-kai Li,et al.  Regional brain levels of monoamines in alcohol-preferring and -nonpreferring lines of rats , 1982, Pharmacology Biochemistry and Behavior.

[38]  H. de Wit,et al.  Reward discounting as a measure of impulsive behavior in a psychiatric outpatient population. , 2000, Experimental and clinical psychopharmacology.

[39]  H. de Wit,et al.  Determination of discount functions in rats with an adjusting-amount procedure. , 1997, Journal of the experimental analysis of behavior.

[40]  H Rachlin,et al.  Commitment, choice and self-control. , 1972, Journal of the experimental analysis of behavior.

[41]  J. Patton,et al.  Factor structure of the Barratt impulsiveness scale. , 1995, Journal of clinical psychology.

[42]  Russell A. Barkley,et al.  ADHD and The Nature of Self-Control , 1997, Journal of Cognitive Psychotherapy.

[43]  D. Cohen,et al.  Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma. , 1981, Clinical chemistry.

[44]  C. Robert Cloninger,et al.  Neurogenetic adaptive mechanisms in alcoholism. , 1987, Science.

[45]  R. Gerner,et al.  The dexamethasone suppression test and response to somatic treatment: a review. , 1986, The Journal of clinical psychiatry.

[46]  G. Logan,et al.  Impulsivity and Inhibitory Control , 1997 .

[47]  C. Benkelfat,et al.  Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. , 1994, Archives of general psychiatry.

[48]  Nancy C. Andreasen,et al.  The family history method using diagnostic criteria , 1978 .

[49]  A. Young,et al.  Rapid depletion of plasma tryptophan: a review of studies and experimental methodology , 1997, Journal of psychopharmacology.

[50]  N C Andreasen,et al.  The family history method using diagnostic criteria. Reliability and validity. , 1977, Archives of general psychiatry.

[51]  R. Pihl,et al.  A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males , 2004, Psychopharmacology.

[52]  G. Logan On the ability to inhibit thought and action , 1984 .

[53]  C. Naranjo,et al.  Modulation of ethanol intake by serotonin uptake inhibitors. , 1986, The Journal of clinical psychiatry.

[54]  T. Robbins,et al.  Central serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination , 1999, Behavioural Brain Research.

[55]  J. T. Coull,et al.  Tryptophan depletion in normal volunteers produces selective impairments in learning and memory , 1994, Neuropharmacology.

[56]  M. Linnoila,et al.  Cerebrospinal fluid variables among alcoholics lack seasonal variation , 1991, Acta psychiatrica Scandinavica.