D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5‐hydroxyindoleacetic acid and 3‐methoxy‐4‐hydroxyphenylglycol in alcoholics in Finland and the United States

If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5‐hydroxyindoleacetic acid (5‐HIAA) and 3‐methoxy‐4‐hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5‐HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States.

[1]  J. Kelsoe,et al.  Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism , 1992, Biological Psychiatry.

[2]  G. Uhl,et al.  Current excitement with D2 dopamine receptor gene alleles in substance abuse. , 1992, Archives of general psychiatry.

[3]  P Kocsis,et al.  The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. , 1991, JAMA.

[4]  H. Scheffer,et al.  LINKAGE ANALYSIS IN FAMILIES WITH PROXIMAL SPINAL MUSCULAR-ATROPHY FROM THE NETHERLANDS , 1991 .

[5]  D. Grandy,et al.  Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor. , 1991, Genomics.

[6]  K. Blum,et al.  Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. , 1991, Alcohol.

[7]  P. M. Conneally.  Association between the D2 dopamine receptor gene and alcoholism. A continuing controversy. , 1991, Archives of general psychiatry.

[8]  E P Noble,et al.  Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. , 1991, Archives of general psychiatry.

[9]  C. Robert Cloninger,et al.  Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage. , 1991, Archives of general psychiatry.

[10]  G. Uhl,et al.  The Dopamine D2 Receptor Gene and Alcoholism , 1991 .

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

[12]  M. Linnoila,et al.  Focal application of alcohols elevates extracellular dopamine in rat brain: a microdialysis study , 1991, Brain Research.

[13]  D. Goldman,et al.  Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. , 1990, JAMA.

[14]  M. Moolten,et al.  Oral self-administration of ethanol and not experimenter-administered ethanol facilitates rewarding electrical brain stimulation. , 1990, Alcohol.

[15]  S. Hill,et al.  Segregation analysis of alcoholism in families ascertained through a pair of male alcoholics. , 1990, American journal of human genetics.

[16]  K. Blum,et al.  Allelic association of human dopamine D2 receptor gene in alcoholism. , 1990, JAMA.

[17]  D. Grandy,et al.  The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. , 1989, American journal of human genetics.

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

[19]  J. Bartko,et al.  Relationship of psychobiological variables to recidivism in violent offenders and impulsive fire setters. A follow-up study. , 1989, Archives of general psychiatry.

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

[21]  G. Di Chiara,et al.  Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. , 1986, The Journal of pharmacology and experimental therapeutics.

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

[23]  G. Sedvall,et al.  Time Course for Effects of Sulpiride and Chlorpromazine on Monoamine Metabolite and Prolactin Levels in Cerebrospinal Fluid from Schizophrenic Patients , 1984, Acta psychiatrica Scandinavica. Supplementum.

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

[25]  P. Spano,et al.  Effect of chronic ethanol treatment on adenylate cyclase activity in rat striatum , 1983, Neuroscience Letters.

[26]  M. Scheinin,et al.  Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection. , 1983, Analytical biochemistry.

[27]  G. Gessa,et al.  Differential effect of acute and chronic ethanol on dopamine metabolism in frontal cortex, caudate nucleus and substantia nigra. , 1980, Life sciences.

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

[29]  F. Goodwin,et al.  Cerebrospinal fluid homovanillic acid in male alcoholics: effects of disulfiram. , 1977, Biological psychiatry.

[30]  S H Snyder,et al.  Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs , 1976, Science.

[31]  H. Yamane,et al.  CSF Monoamine Metabolites in Alcoholism: A Comparative Study With Depression , 1974, Folia psychiatrica et neurologica japonica.

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

[33]  T. Hökfelt,et al.  Evidence for dopamine receptor stimulation by apomorphine , 1967, The Journal of pharmacy and pharmacology.

[34]  C. Robert Cloninger,et al.  D2 dopamine receptor gene is associated but not linked with alcoholism. , 1991, JAMA.

[35]  D. Goldman.  Molecular markers for linkage of genetic loci contributing to alcoholism. , 1988, 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.

[36]  C. Robert Cloninger,et al.  Etiologic heterogeneity in alcoholism , 1987, Genetic epidemiology.