Low Central Nervous System Serotonergic Activity Is Traitlike and Correlates with Impulsive Behavior

ABSTRACT: We have used nonhuman primates to examine developmental and behavioral correlates of CNS serotonergic activity, as measured by concentrations of the serotonin metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in the cerebrospinal fluid (CSF). These studies show that interindividual differences in CNS serotonin turnover rate exhibit traitlike qualities and are stable across time and settings, with interindividual differences in CSF 5‐HIAA concentrations showing positive correlations across repeated sampling. Primates with low CNS serotonergic activity exhibit behaviors indicative of impaired impulse control, unrestrained aggression, social isolation, and low social dominance. Maternal and paternal genetic influences play major roles in producing low CNS serotonin functioning, beginning early in life. These genetic influences on serotonin functioning are further influenced by early rearing experiences, particularly parental deprivation.

[1]  M. Linnoila,et al.  CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season , 1997, Psychiatry Research.

[2]  J. Mann,et al.  Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients , 1997, Biological Psychiatry.

[3]  J. Sweeney,et al.  Attempted Suicide Characteristics and Cerebrospinal Fluid Amine Metabolites in Depressed Inpatients , 1996, Neuropsychopharmacology.

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

[5]  P. Goldman-Rakic.  The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[6]  M. Linden,et al.  Is there a suicidality syndrome independent of specific major psychiatric disorder? Results of a split half multiple regression analysis , 1996, Acta psychiatrica Scandinavica.

[7]  M. Linnoila,et al.  A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. , 1996, Alcoholism, clinical and experimental research.

[8]  M. Linnoila,et al.  Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. , 1996, Archives of general psychiatry.

[9]  M. Linnoila,et al.  A nonhuman primate model of type II alcoholism? Part 2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. , 1996, Alcoholism, clinical and experimental research.

[10]  H. Brooks,et al.  Evolution and overview of classical transmitter molecules and their receptors , 1996, Parasitology.

[11]  D. Hommer,et al.  Cerebral glucose metabolism, CSF 5-HIAA levels, and aggressive behavior in rhesus monkeys. , 1995, The American journal of psychiatry.

[12]  J. Lönnqvist,et al.  Suicide among female adolescents: characteristics and comparison with males in the age group 13 to 22 years. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[13]  D. Fergusson,et al.  Suicide attempts and suicidal ideation in a birth cohort of 16-year-old New Zealanders. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  J. John Mann,et al.  Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims , 1995, Brain Research.

[15]  A. Roy,et al.  Attempted suicide among living co-twins of twin suicide victims. , 1995, The American journal of psychiatry.

[16]  M. Linnoila,et al.  Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates. , 1995, The American journal of psychiatry.

[17]  S. Peroutka.  5-Hydroxytryptamine receptors in vertebrates and invertebrates: Why are there so many? , 1994, Neurochemistry International.

[18]  M. Linnoila,et al.  Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. , 1994, The American journal of psychiatry.

[19]  D. Fergusson,et al.  The childhoods of multiple problem adolescents: a 15-year longitudinal study. , 1994, Journal of child psychology and psychiatry, and allied disciplines.

[20]  B. Brismar,et al.  Characteristics of violent alcoholics. , 1994, Alcohol and alcoholism.

[21]  D. Abbott,et al.  Long-term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys. , 1994, Developmental psychobiology.

[22]  B. Brismar,et al.  Hormone levels and personality traits in abusive and suicidal male alcoholics. , 1994, Alcoholism, clinical and experimental research.

[23]  J. Palacios,et al.  Localization of 5-HT1B, 5-HT1Dα, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain , 1994, Neuropharmacology.

[24]  G. Mcclearn,et al.  Heritability of irritable impulsiveness: A study of twins reared together and apart , 1993, Psychiatry Research.

[25]  D. Goldman,et al.  Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in rhesus monkeys (Macaca mulatta). , 1993, Archives of general psychiatry.

[26]  R. Pihl,et al.  Risk for alcoholism, antisocial behavior, and response perseveration. , 1993, Journal of clinical psychology.

[27]  M. Raleigh,et al.  Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences. , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[28]  M. Linnoila,et al.  Factors Associated with Recidivism in a Criminal Population , 1992, The Journal of nervous and mental disease.

[29]  S. Møller,et al.  Serotonin, carbohydrates, and atypical depression. , 1992, Pharmacology & toxicology.

[30]  M. Linnoila,et al.  A longitudinal assessment of CSF monoamine metabolite and plasma cortisol concentrations in young rhesus monkeys , 1992, Biological Psychiatry.

[31]  J. Rapoport,et al.  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? , 1992, Archives of general psychiatry.

[32]  T. Brewerton,et al.  Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes. , 1992, Archives of general psychiatry.

[33]  Laurie A. Miller,et al.  Impulsivity, risk-taking, and the ability to synthesize fragmented information after frontal lobectomy , 1992, Neuropsychologia.

[34]  E. Azmitia,et al.  Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. , 1991, The Journal of clinical psychiatry.

[35]  N. K. Popova,et al.  Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes , 1991, Pharmacology Biochemistry and Behavior.

[36]  K. Sher,et al.  Characteristics of children of alcoholics: putative risk factors, substance use and abuse, and psychopathology. , 1991, Journal of abnormal psychology.

[37]  Michael J. Raleigh,et al.  Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys , 1991, Brain Research.

[38]  P. Goldman-Rakic,et al.  Myelo‐ and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca , 1991, The Journal of comparative neurology.

[39]  M. Linnoila,et al.  Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  W. Kaye,et al.  Altered serotonin activity in anorexia nervosa after long-term weight restoration. Does elevated cerebrospinal fluid 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior? , 1991, Archives of general psychiatry.

[41]  D. Goldman,et al.  Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls. , 1991, Archives of general psychiatry.

[42]  R. Ulrich,et al.  A preliminary trial of fluoxetine in refractory borderline patients. , 1991, Journal of clinical psychopharmacology.

[43]  V. Arango,et al.  Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. , 1990, Archives of general psychiatry.

[44]  R. Bonner,et al.  Psychosocial vulnerability, life stress, and suicide ideation in a jail population: a cross-validation study. , 1990, Suicide & life-threatening behavior.

[45]  T. Brewerton,et al.  Eating disorders and depression: Is there a serotonin connection? , 1990, Biological Psychiatry.

[46]  P. Goldman-Rakic,et al.  Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  J. Rapoport,et al.  Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. , 1990, Archives of general psychiatry.

[48]  R. Plutchik,et al.  Interrelationships among anxiety, aggression, impulsivity, and mood: A serotonergically linked cluster? , 1990, Psychiatry Research.

[49]  C. Naranjo,et al.  Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers , 1990, Clinical pharmacology and therapeutics.

[50]  B. Winblad,et al.  Ventricular Cerebrospinal Fluid Monoamine Transmitter and Metabolite Concentrations Reflect Human Brain Neurochemistry in Autopsy Cases , 1990, Journal of neurochemistry.

[51]  A. Roy,et al.  CSf studies on alcoholism and related behaviours , 1989, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[52]  W. Greenough,et al.  Effects of complex experience on somatic growth and organ development in rats. , 1989, Developmental psychobiology.

[53]  J. Barrett,et al.  Behavioral studies with anxiolytic drugs. VI. Effects on punished responding of drugs interacting with serotonin receptor subtypes. , 1989, The Journal of pharmacology and experimental therapeutics.

[54]  G. Kraemer,et al.  A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys. , 1989, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[55]  J. Bartko,et al.  Psychobiological concomitants of history of suicide attempts among violent offenders and impulsive fire setters. , 1989, Archives of general psychiatry.

[56]  N. K. Popova,et al.  Behavior, adrenocortical activity, and brain monoamines in Norway rats selected for reduced aggressiveness towards man , 1989, Pharmacology Biochemistry and Behavior.

[57]  H. Conte,et al.  Correlates of suicide and violence risk: III. A two-stage model of countervailing forces , 1989, Psychiatry Research.

[58]  K. Davis,et al.  Correlations post-mortem between ventricular CSF and cortical tissue concentrations of MHPG, 5-HIAA and HVA in Alzheimer's disease , 1989, Biological Psychiatry.

[59]  M. Kruesi.  Cruelty to animals and CSF 5HIAA , 1989, Psychiatry Research.

[60]  R. Heinrichs.  Frontal cerebral lesions and violent incidents in chronic neuropsychiatrie patients , 1989, Biological Psychiatry.

[61]  R. Bonner,et al.  A prospective investigation of suicidal ideation in college students: a test of a model. , 1988, Suicide & life-threatening behavior.

[62]  R. Pihl,et al.  The effect of raising or lowering tryptophan levels on aggression in vervet monkeys , 1987, Pharmacology Biochemistry and Behavior.

[63]  H. Moss.  Serotonergic activity and disinhibitory psychopathy in alcoholism. , 1987, Medical hypotheses.

[64]  W. Greenough,et al.  Experience and brain development. , 1987, Child development.

[65]  F. Goodwin,et al.  Cerebrospinal fluid monoamine metabolite levels in male arsonists. , 1987, Archives of general psychiatry.

[66]  S. Kety,et al.  Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. , 1986, Archives of general psychiatry.

[67]  B. McEwen,et al.  Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. , 1986, Archives of general psychiatry.

[68]  D. W. Goodwin,et al.  A prospective study of young men at high risk for alcoholism. Social and psychological characteristics. , 1986, Archives of general psychiatry.

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

[70]  A. Roy.  Suicide in Twins , 1986, Archives of general psychiatry.

[71]  B. Shaywitz,et al.  Cerebrospinal fluid monoamine precursor and metabolite levels in children treated for leukemia: Age and sex effects and individual variability , 1986, Biological Psychiatry.

[72]  M. Raleigh,et al.  Dominant social status facilitates the behavioral effects of serotonergic agonists , 1985, Brain Research.

[73]  T. Insel,et al.  Obsessive-compulsive disorder and serotonin: Is there a connection? , 1985, Biological Psychiatry.

[74]  M. Stanley,et al.  Correlations between aminergic metabolites simultaneously obtained from human CSF and brain. , 1985, Life sciences.

[75]  S. Borg,et al.  5-Hydroxyindoleacetic acid in cerebrospinal fluid in alcoholic patients under different clinical conditions. , 1985, Alcohol.

[76]  M. Åsberg,et al.  Homicide, suicide and CSF 5‐HIAA , 1985, Acta psychiatrica Scandinavica.

[77]  W. Kaye,et al.  Differences in brain serotonergic metabolism between nonbulimic and bulimic patients with anorexia nervosa. , 1984, The American journal of psychiatry.

[78]  M. Åsberg,et al.  CSF monoamine metabolites of depressed patients during illness and after recovery , 1984, Acta psychiatrica Scandinavica.

[79]  F. Goodwin,et al.  CSF 5-hydroxyindoleacetic acid levels in suicidal schizophrenic patients. , 1984, The American journal of psychiatry.

[80]  M Linnoila,et al.  Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. , 1983, Life sciences.

[81]  M. Aratô,et al.  Amine metabolites, neuroendocrine findings, and personality dimensions as correlates of suicidal behavior , 1983, Psychiatry Research.

[82]  J. Mann,et al.  INCREASED SEROTONIN-2 BINDING SITES IN FRONTAL CORTEX OF SUICIDE VICTIMS , 1983, The Lancet.

[83]  G. Shaw,et al.  Tiapride in tardive dyskinesia. , 1982, Psychopharmacology bulletin.

[84]  M. Åsberg,et al.  Urinary excretion of 5‐hydroxyindoleacetic acid – no relationship to the level in cerebrospinal fluid , 1982, Acta psychiatrica Scandinavica.

[85]  W. J. Klein,et al.  Aggression, suicide, and serotonin: relationships to CSF amine metabolites. , 1982, The American journal of psychiatry.

[86]  H. D. Steklis,et al.  Effects of orbitofrontal and temporal neocortical lesions on the affiliative behavior of vervet monkeys (Cercopithecus aethiops sabaeus) , 1981, Experimental Neurology.

[87]  M. Åsberg,et al.  Clomipramine treatment of obsessive-compulsive disorder. I. A controlled clinical trial. , 1980, Archives of general psychiatry.

[88]  M. Raleigh,et al.  Serotonergic influences on the social behavior of vervet monkeys (Cercopithecus aethiops sabaeus) , 1980, Experimental Neurology.

[89]  B. Brown.  The Council on National Affairs , 1980 .

[90]  Frederick K. Goodwin,et al.  Aggression in humans correlates with cerebrospinal fluid amine metabolites , 1979, Psychiatry Research.

[91]  H. D. Steklis,et al.  The effects of orbitofrontal lesions on the aggressive behavior of vervet monkeys (Cercopithecus aethiops sabaeus) , 1979, Experimental Neurology.

[92]  R. Caprioli,et al.  Biogenic amine metabolism in tourette syndrome , 1979, Annals of neurology.

[93]  J. Nathanson,et al.  Central biogenic amine metabolism in children with the syndrome of chronic multiple tics of Gilles de la Tourette: norepinephrine, serotonin, and dopamine. , 1979, Journal of the American Academy of Child Psychiatry.

[94]  Gerald L. Brown,et al.  Alcohol and central serotonin metabolism in man. , 1979, Archives of general psychiatry.

[95]  B. Shaywitz,et al.  Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration. , 1978, Archives of general psychiatry.

[96]  T. V. Woerkom,et al.  DIFFERENCE IN NEUROTRANSMITTER METABOLISM IN FRONTOTEMPORAL-LOBE CONTUSION AND DIFFUSE CEREBRAL CONTUSION , 1977, The Lancet.

[97]  M. Åsberg,et al.  5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? , 1976, Archives of general psychiatry.

[98]  B. Shaywitz,et al.  Biogenic amines in autistic and atypical children. Cerebrospinal fluid measures of homovanillic acid and 5-hydroxyindoleacetic acid. , 1974, Archives of general psychiatry.

[99]  H. Jarvie.  FRONTAL LOBE WOUNDS CAUSING DISINHIBITION , 1954, Journal of neurology, neurosurgery, and psychiatry.

[100]  M. Linnoila,et al.  Stability of Interindividual Differences in Serotonin Function and Its Relationship to Severe Aggression and Competent Social Behavior in Rhesus Macaque Females , 1996, Neuropsychopharmacology.

[101]  K. Turlejski,et al.  Evolutionary ancient roles of serotonin: long-lasting regulation of activity and development. , 1996, Acta neurobiologiae experimentalis.

[102]  D. Goldman,et al.  Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. , 1994, Archives of general psychiatry.

[103]  S. Hamburger,et al.  Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[104]  N. Popova,et al.  Role of 5HT1A receptors in a variety of kinds of aggressive behavior in wild rats and counterparts selected for low defensiveness towards man , 1992 .

[105]  E. Coccaro,et al.  Impulsive aggression and central serotonergic system function in humans: an example of a dimensional brain‐behavior relationship , 1992, International clinical psychopharmacology.

[106]  M. Stanley,et al.  Biological studies and markers in suicide and attempted suicide. , 1991, International clinical psychopharmacology.

[107]  N. K. Popova,et al.  Serotonin metabolism and serotonergic receptors in Norway rats selected for low aggressiveness to man , 1991 .

[108]  M. Linnoila,et al.  Serotonin in early onset, male alcoholics with violent behaviour. , 1990, Annals of medicine.

[109]  B. Olivier,et al.  Serenics, serotonin and aggression. , 1990, Progress in clinical and biological research.

[110]  R. Ulrich,et al.  Fluoxetine trial in borderline personality disorder. , 1990, Psychopharmacology bulletin.

[111]  W. Mcbride,et al.  Serotonin and ethanol preference. , 1989, Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism.

[112]  C. Naranjo,et al.  Serotonin uptake inhibitors attenuate ethanol intake in problem drinkers. , 1989, Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism.

[113]  K. Gill,et al.  Serotonin Uptake Blockers and Voluntary Alcohol Consumption , 1989 .

[114]  D. Gorelick.  Serotonin uptake blockers and the treatment of alcoholism. , 1989, Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism.

[115]  K. Miczek,et al.  Brain 5-HT and inhibition of aggressive behavior in animals: 5-HIAA and receptor subtypes. , 1989, Psychopharmacology bulletin.

[116]  K. Gill,et al.  Serotonin uptake blockers and voluntary alcohol consumption. A review of recent studies. , 1989, Recent developments in alcoholism : an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism.

[117]  S. Suomi,et al.  Temperamental reactivity in non-human primates. , 1989 .

[118]  C. Freeman,et al.  Fluoxetine as a treatment for bulimia nervosa. , 1987, International journal of obesity.

[119]  P. Goldman-Rakic.  Motor control function of the prefrontal cortex. , 1987, Ciba Foundation symposium.

[120]  I. Bernstein,et al.  Modification of aggression through socialization and the special case of adult and adolescent male rhesus monkeys (Macaca mulatta) , 1986, American journal of primatology.

[121]  G. Sedvall,et al.  Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals--a genetic study. , 1986, Journal of psychiatric research.

[122]  E. Azmitia,et al.  The primate serotonergic system: a review of human and animal studies and a report on Macaca fascicularis. , 1986, Advances in neurology.

[123]  M. Åsberg,et al.  Cerebrospinal fluid studies in suicide. An overview. , 1986, Annals of the New York Academy of Sciences.

[124]  M. Raleigh,et al.  Animal analogues of ostracism: Biological mechanisms and social consequences , 1986 .

[125]  M. Raleigh,et al.  Male dominance, serotonergic systems, and the behavioral and physiological effects of drugs in vervet monkeys (Cercopithecus aethiops sabaeus). , 1983, Progress in clinical and biological research.

[126]  S. Suomi.  The development of social competence by rhesus monkeys. , 1982, Annali dell'Istituto superiore di sanita.

[127]  F. Goodwin,et al.  Human aggression and suicide: their relationship to neuropsychiatric diagnoses and serotonin metabolism. , 1982, Advances in biochemical psychopharmacology.

[128]  C. Bramblett,et al.  Effects of rearing on aggression and subordination in papio monkeys , 1981, American journal of primatology.

[129]  G. Mitchell.  Abnormal Behavior in Primates , 1970 .

[130]  H. Harlow.  Age-Mate or Peer Affectional System , 1969 .

[131]  H. Harlow.  Chapter 8 – The Affectional Systems1 , 1965 .

[132]  H. Harlow,et al.  The Affectional Systems , 1965 .