Psychopharmacology

, Volume 174, Issue 4, pp 463–476

Human genetics of plasma dopamine β-hydroxylase activity: applications to research in psychiatry and neurology

Review

Abstract

Rationale

Norepinephrine (NE) is a key neurotransmitter in the central and peripheral nervous systems. Dopamine β-hydroxylase (DβH) catalyzes the synthesis of NE from dopamine (DA) and occurs in the plasma as a stable heritable trait. Studies of this trait have been useful in psychiatric and neurological research.

Objective

To selectively and critically review the literature on plasma DβH, and on recent progress understanding the molecular genetic basis for its inheritance. Based on this review, directions for future research in psychiatry and neurology will be suggested.

Methods

We selectively review the literature on the biochemical and molecular genetics of plasma DβH activity, as well as research on plasma and cerebrospinal fluid (CSF) DβH in psychiatric and neurological disorders.

Results

Strong evidence implicates DBH, the structural locus encoding DβH enzyme, as the major quantitative trait locus influencing plasma DβH activity, with one single nucleotide polymorphism (SNP) accounting for up to 50% of the variance. Mutations at DBH appear to be responsible for the rare syndrome of DβH deficiency. Some biochemical and genetic studies suggest associations between low plasma or CSF DβH and psychotic symptoms in several psychiatric disorders. Studies combining genotyping at DBH with biochemical measurement of plasma DβH have proven useful in studies of schizophrenia, cocaine-induced paranoia (CIP), depression, attention deficit hyperactivity disorder, and alcoholism. Such studies may also elucidate the contribution of noradrenergic dysfunction to a variety of symptoms in Parkinson’s disease and other degenerative neurological disorders.

Conclusions

A model is proposed, in which lower levels of DβH protein may lead to elevated ratios of DA to NE. This model may explain associations between lower plasma DβH activity and vulnerability to psychotic symptoms. Genotype-controlled analysis of plasma DβH holds promise for promoting further progress in research on psychiatric and neurological disorders.

Keywords

Catecholamines Norepinephrine Quantitative trait locus Sympathetic nervous system Psychosis Depression Alcoholism Attention deficit hyperactivity disorder Parkinson’s disease Hypotension 

References

  1. Amaral DG, Sinnamon HM (1977) The locus coeruleus: neurobiology of a central noradrenergic nucleus. Prog Neurobiol 9:147–196CrossRefPubMedGoogle Scholar
  2. Anand A, Charney DS (2000) Norepinephrine dysfunction in depression. J Clin Psychiatry 61:16–24Google Scholar
  3. Arango V, Underwood MD, Mann JJ (1994) Fewer pigmented neurons in the locus coeruleus of uncomplicated alcoholics. Brain Res 650:1–8CrossRefPubMedGoogle Scholar
  4. Arnsten AF (2000a) Genetics of childhood disorders: XVIII. ADHD. Part 2. Norepinephrine has a critical modulatory influence on prefrontal cortical function. J Am Acad Child Adolesc Psychiatry 39:1201–1203Google Scholar
  5. Arnsten AF (2000b) Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanisms. Prog Brain Res 126:183–192PubMedGoogle Scholar
  6. Arrufat FJ, Diaz R, Queralt R, Navarro V, Marcos T, Massana G, Massana J, Ballesta F, Oliva R (2000) Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia. Am J Med Genet 96:88–92CrossRefPubMedGoogle Scholar
  7. Asamoah A, Wilson AF, Elston RC, Dalferes E Jr, Bereson GS (1987) Segregation and linkage analyses of dopamine β-hydroxylase activity in a large six-generation pedigree. Am J Med Genet 27:613–621PubMedGoogle Scholar
  8. Bezard E, Jaber M, Gonon F, Boireau A, Bloch B, Gross CE (2000) Adaptive changes in the nigrostriatal pathway in response to increased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration in the mouse. Eur J Neurosci 12:2892–2900CrossRefPubMedGoogle Scholar
  9. Biagionni I, Robertson D (1987) Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency. Lancet 2:1170–1172CrossRefPubMedGoogle Scholar
  10. Bowden CL, Deutsch CK, Swanson JM (1988) Plasma dopamine-beta-hydroxylase and platelet monoamine oxidase in attention deficit disorder and conduct disorder. J Am Acad Child Adolesc Psychiatry 27:171–174PubMedGoogle Scholar
  11. Braune S, Reinhardt M, Schnitzer R, Riedel A, Lucking CH (1999) Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 53:1020–1025PubMedGoogle Scholar
  12. Burke WJ, Li SW, Schmitt CA, Xia P, Chung HD, Gillespie KN (1999) Accumulation of 3,4-dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase A metabolite of norepinephrine, in locus ceruleus cell bodies in Alzheimer’s disease: mechanism of neuron death. Brain Res 816:633–637CrossRefPubMedGoogle Scholar
  13. Cash R, Dennis T, L’Heureux R, Raisman R, Javoy-Agid F, Scatton B (1987) Parkinson’s disease and dementia: norepinephrine and dopamine in locus ceruleus. Neurology 37:42–46PubMedGoogle Scholar
  14. Chambers KJ, Tonkin LA, Chang E, Shelton DN, Linskens MH, Funk WD (1998) Identification and cloning of a sequence homologue of dopamine beta-hydroxylase. Gene 218:111–120CrossRefPubMedGoogle Scholar
  15. Coyle JT, Wooten GF, Axelrod J (1974) Evidence for extranoradrenergic dopamine-beta-hydroxylase activity in rat salivary gland. J Neurochem 22:923–929PubMedGoogle Scholar
  16. Craig SP, Buckle VJ, Lamouroux A, Mallet J, Craig IW (1988) Localization of dopamine beta hydroxylase (DBH) gene to chromosome 9q34. Cytogenet Cell Genet 48:48–50PubMedGoogle Scholar
  17. Crow TJ (1985) The two-syndrome concept: origins and current status. Schizophr Bull 11:471–486Google Scholar
  18. Cubells JF, Kobayashi K, Nagatsu T, Kidd KK, Kidd JR, Calafell F, Kranzler HR, Ichinose H, Gelernter J (1997) Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH). Am J Med Genet 74:374–379PubMedGoogle Scholar
  19. Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O’Connor DT, Price LH, Malison R, Rao PA, Kobayashi K, Nagatsu T, Gelernter J (1998) Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 102:533–540CrossRefPubMedGoogle Scholar
  20. Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, Gelernter J (2000) A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5:56–63CrossRefPubMedGoogle Scholar
  21. Cubells JF, Price LH, Meyers BS, Anderson GM, Zabetian CP, Alexopoulos, Nelson JC, Sanacora G, Kirwin P, Carpenter L, Malison RT, Gelernter J (2002) Genotype-controlled analysis of plasma dopamine β-hydroxylase activity in psychotic unipolar major depression. Biol Psychiatry 51:358–364PubMedGoogle Scholar
  22. Daly G, Hawi Z, Fitzgerald M, Gill M (1999) Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry 4:192–196Google Scholar
  23. DeVoto P, Flore G, Pani L, Gessa GL (2001) Evidence for co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex. Mol Psychiatry 6:657–664Google Scholar
  24. Druschky A, Hilz MJ, Platsch G, Radespiel-Troger M, Druschky K, Kuwert T, Neundorfer B (2000) Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT. J Neurol Sci 175:3–12CrossRefPubMedGoogle Scholar
  25. Dunnette J, Weinshilboum RM (1976) Human serum dopamine-β-hydroxylase: correlation of enzyme activity with immunoreactive protein in genetically defined samples. Am J Hum Genet 28:155–166PubMedGoogle Scholar
  26. Ebstein RP, Park DH, Freedman LS, Levitz SM, Ouchi T, Goldstein M (1973) A radioimmunoassay of human circulatory dopamine-beta-hydroxylase. Life Sci 13:769–784CrossRefPubMedGoogle Scholar
  27. Elston RC, Namboodiri KK, Hames CG (1979) Segregation and linkage analyses of dopamine β-hydroxylase activity. Hum Hered 29:284–292PubMedGoogle Scholar
  28. Esler M, Rumantir M, Kaye D, Jennings G, Hastings J, Socratous F, Lambert G (2001) Sympathetic nerve biology in essential hypertension. Clin Exp Pharmacol Physiol 28:986–989CrossRefPubMedGoogle Scholar
  29. Fischer HD, Rudolph E, Schmidt J, Hilse H, Oehme P, Piesche L (1980) Interaction at the synaptic level of fusaric acid with neurotransmitters. Acta Biol Med Germ 39:935–940PubMedGoogle Scholar
  30. Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63:844–914PubMedGoogle Scholar
  31. Forstl H, Levy R, Burns A, Luthert P, Cairns N (1994) Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer’s disease—a hypothesis. Pharmacopsychiatry 27:11–15Google Scholar
  32. Frecska BG, Horváth S, Zádor G, Arató M (1990) Predicting neuroleptic response from a combination of multilevel variables in acute schizophrenic patients. Acta Psychiatr Scand 82:408–412PubMedGoogle Scholar
  33. Freeman R, Landsberg L, Young J (1999) The treatment of neurogenic orthostatic hypotension with 3,4-dl-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial. Neurology 53:2151–2157PubMedGoogle Scholar
  34. Fujita K, Ito T, Maruta K, Teradaira R, Beppu H, Nakagami Y, Kato Y, Nagatsu T, Kato T (1978) Serum dopamine-β-hydroxylase in schizophrenic patients. J Neurochem 30:1569–1572PubMedGoogle Scholar
  35. Gaspar P, Gray F (1984) Dementia in idiopathic Parkinson’s disease, a neuropathological study of 32 cases. Acta Neuropathol 64:43–52PubMedGoogle Scholar
  36. Gelernter J, Gejman PV, Bisghini S, Kidd KK (1991) Sequence tagged site (STS) Taq1 RFLP at dopamine β-hydroxylase (DBH). Nucl Acids Res 19:1957Google Scholar
  37. Goldin LR, Gershon ES, Lake CR, Murphy DL, McGinniss M, Sparkes RS (1982) Segregation and linkage studies of plasma dopamine-beta-hydroxylase (DBH), erythrocyte catechol-O-methyl transferase (COMT) and platelet monoamine oxidase (MAO): possible linkage between the ABO locus and a gene controlling DBH activity. Am J Hum Genet 34:250–262PubMedGoogle Scholar
  38. Grace AA, Gerfen CR, Aston-Jones G (1998) Catecholamines in the central nervous system. Overview Adv Pharmacol 42:655–670Google Scholar
  39. Grobecker H, Roizen MF, Jacobowitz DM, Kopin IJ (1977) Effect of prolonged treatment with adrenergic neuron blocking drugs on sympathoadrenal reactivity in rats. Eur J Pharmacol 46:125–133CrossRefPubMedGoogle Scholar
  40. Grzanna R, Coyle JT (1978) Absence of a relationship between sympathetic neuronal activity and tulnover of serum dopamine-β-hydroxylase. Naunyn-Schmiedeberg’s Arch Pharmakol Exp Pathol 304:231–236Google Scholar
  41. Hartmann E, Keller-Teschke M (1979) The psychological effects of dopamine-β-hydroxylase inhibition in normal subjects. Biol Psychiatry 14:455–462PubMedGoogle Scholar
  42. Heiss G, Tyroler HA, Gunnells JC, McGuffin WL, Hames CG (1980) Dopamine-β-hydroxylase in a bi-racial community: demographic, cardiovascular and familial factors. J Chron Dis 33:301–310PubMedGoogle Scholar
  43. Holroyd KA, Penzien DB, Cordingley GE (1991) Propranolol in the management of recurrent migraine: a meta-analytic review. Headache 31:333–340PubMedGoogle Scholar
  44. Hoogendijk WJ, Feenstra MG, Botterblom MH, Gilhuis J, Sommer IE, Kamphorst W, Eikelenboom P, Swaab DF (1999) Increased activity of surviving locus ceruleus neurons in Alzheimer’s disease. Ann Neurol 45:82–91CrossRefPubMedGoogle Scholar
  45. Hoyle GW, Mercer EH, Palmiter RD, Brinster RL (1994) Cell-specific expression from the human dopamine beta-hydroxylase promoter in transgenic mice is controlled via a combination of positive and negative regulatory elements. J Neurosci 14:2455–2463PubMedGoogle Scholar
  46. Hurst JH, LeWitt PA, Burns RS, Foster NL, Lovenberg W (1985) CSF dopamine-beta-hydroxylase activity in Parkinson’s disease. Neurology 35:565–568PubMedGoogle Scholar
  47. Ishiguro H, Kim KT, Joh TH, Kim KS (1993) Neuron-specific expression of the human dopamine beta-hydroxylase gene requires both the cAMP-response element and a silencer region. J Biol Chem 268:17987–17994PubMedGoogle Scholar
  48. Ishii A, Kobayashi K, Kiuchi K, Nagatsu T (1991) Expression of two forms of human dopamine-beta-hydroxylase in COS cells. Neurosci Lett 125:25–28CrossRefPubMedGoogle Scholar
  49. Jansen M, Boomsma F, van den Heuvel B, Deinum J, Steenbergen-Spanjers G, Wevers R (2001) Mutation analysis in two patients with congenital dopamine beta-hydroxylase deficiency, abstract III-ICS-10. Presented at the Ninth International Catecholamine Symposium, Kyoto, JapanGoogle Scholar
  50. Joyce JN, Smutzer G, Whitty CJ, Myers A, Bannon MJ (1997) Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson’s, Alzheimer’s with parkinsonism, and Alzheimer’s disease. Mov Disord 12:885–897PubMedGoogle Scholar
  51. Kaufman S, Friedman S (1965) Dopamine-beta-hydroxylase. Pharmacol Rev 17:71–100PubMedGoogle Scholar
  52. Kent JM, Mathew SJ, Gorman JM (2002) Molecular targets in the treatment of anxiety. Biol Psychiatry 52:1008–1030CrossRefPubMedGoogle Scholar
  53. Kim C-Y, Zabetian CP, Cubells JF, Cho S, Biaggioni I, Cohen BM, Robertson D, Kim K-S (2002) Mutations in the dopamine β-hydroxylase gene are associated with human dopamine β-hydroxylase deficiency. Am J Med Genet 108:140–147CrossRefPubMedGoogle Scholar
  54. Kobayashi K, Kiuchi K, Ishii A, Kaneda N, Kurosawa Y, Fujita K, Nagatsu T (1989) Human dopamine β-hydoxylase gene: two mRNA types having different 3-terminal regions are produced through alternative polyadenylation. Nucl Acids Res 17:1089–1102Google Scholar
  55. Köhnke M, Zabetian CP, Anderson GM, Kolb W, Gaertner I, Buchkremer G, Vonthein R, Schick S, Lutz U, Köhnke AM, Cubells JF (2002) A genotype-controlled analysis of plasma dopamine β-hydroxylase in healthy subjects and alcoholics: evidence for alcohol-related differences in noradrenergic function. Biol Psychiatry 52:1151–1158CrossRefPubMedGoogle Scholar
  56. Lamouroux A, Vigny A, Faucon Biguet N, Darmon MC, Franck R, Henry JP, Mallet J (1987) The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J 6:3931–3937PubMedGoogle Scholar
  57. Li B, Tsing S, Kosaka AH, Nguyen B, Osen EG, Bach C, Chan H, Barnett J (1996) Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2 cells. Biochem J 313:57–64PubMedGoogle Scholar
  58. Lieberman AN, Freedman LS, Goldstein M (1972) Serum dopamine-beta-hydroxylase activity in patients with Huntington’s chorea and Parkinson’s disease. Lancet 1:153–154CrossRefPubMedGoogle Scholar
  59. Long JC, Williams RC, Urbanek M (1995) An E–M algorithm and testing strategy for multiple-locus haplotypes. Am J Hum Genet 56:799–180PubMedGoogle Scholar
  60. Lykouras E, Markianos M, Malliaras D, Stefanis C (1988) Neurochemical variables in delusional depression. Am J Psychiatry 145:214–217PubMedGoogle Scholar
  61. Magalhaes M, Wenning GK, Daniel SE, Quinn NP (1995) Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson’s disease—a retrospective comparison. Acta Neurol Scand 91:98–102PubMedGoogle Scholar
  62. Major LF, Lerner P, Ballenger JC, Brown GL, Goodwin FK, Lovenberg W (1979) Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis. Biol Psychiatry 14:337–44PubMedGoogle Scholar
  63. Mann DM, Yates PO (1983) Pathological basis for neurotransmitter changes in Parkinson’s disease. Neuropathol Appl Neurobiol 9:3–19PubMedGoogle Scholar
  64. Man in’t Veld AJ, Boomsma F, Moleman P, Schalekamp MADH (1987) Congenital dopamine-β-hydroxylase deficiency. A novel orthostatic syndrome. Lancet 1:183–188PubMedGoogle Scholar
  65. Markianos M, Hadjikonstantinou M, Sfagos C (1981) Normal plasma dopamine-beta-hydroxylase in non-treated and treated Parkinson patients. Acta Neurol Scand 63:267–272PubMedGoogle Scholar
  66. Mathias CJ, Bannister RB, Cortelli P, Heslop K, Polak JM, Raimbach S, Springall DR, Watson L (1990) Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase. Q J Med 75:617–633PubMedGoogle Scholar
  67. McMahon A, Sabban EL (1992) Regulation of expression of dopamine beta-hydroxylase in PC12 cells by glucocorticoids and cyclic AMP analogues. J Neurochem 59:2040–2047PubMedGoogle Scholar
  68. Meltzer HY, Hyong HW, Carroll BJ, Russo P (1976) Serum dopamine-β-hydroxylase in the affective psychoses and schizophrenia: Decreased activity in unipolar psychotically depressed patients. Arch Gen Psychiatry 33:585–591PubMedGoogle Scholar
  69. Meltzer HY, Nasr SJ, Tong C (1980) Serum dopamine-β-hydroxylase in schizophrenia. Biol Psychiatry 15:781–788PubMedGoogle Scholar
  70. Meszaros K, Lenzinger E, Fureder T, Hornik K, Willinger U, Stompe T, Heiden AM, Resinger E, Fathi N, Gerhard E, Fuchs K, Miller-Reiter E, Pfersmann V, Sieghart W, Aschauer HN, Kasper S (1996) Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study. Psychiatr Genet 6:17–22PubMedGoogle Scholar
  71. Meyers BS, Alexopoulos GS, Kakuma T, Tirumalasetti F, Gabriele M, Alpert S, Bowden C, Meltzer HY (1999) Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression. Biol Psychiatry 45:448–452CrossRefPubMedGoogle Scholar
  72. Mitler MM, Hajdukovic R, Erman MK (1993) Treatment of narcolepsy with methamphetamine. Sleep 16:306–317PubMedGoogle Scholar
  73. Mogi M, Harada M, Kojima K, Inagaki H, Kondo T, Narabayashi H, Arai T, Teradaira R, Fujita K, Kiuchi K, Nagatsu T (1988) Sandwich enzyme immunoassay of dopamine beta-hydroxylase in cerebrospinal fluid from control and parkinsonian patients. Neurochem Int 12:187–191CrossRefGoogle Scholar
  74. Moore RY, Bloom FE (1979) Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci 2:113–168CrossRefPubMedGoogle Scholar
  75. Mód L, Rihmer Z, Magyar I, Arató M, Alföldi A, Bagdy G (1986) Serum DBH activity in psychotic vs nonpsychotic unipolar and bipolar depression. Psychiatry Res 19:331–333CrossRefPubMedGoogle Scholar
  76. Müller Smith K, Daly M, Fischer M, Yiannoutsos CT, Bauer L, Barkley R, Navia BA (2003) Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study. Am J Med Genet Part B (Neuropsychiatr Genet) 119B:77–85Google Scholar
  77. Nagatsu T, Udenfriend S (1972) Photometric assay of dopamine-β-hydroxylase activity in rat serum. Clin Chem 18:980–983PubMedGoogle Scholar
  78. Nagatsu T, Kato T, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Narabayashi H (1979) Catecholamine-related enzymes in the brain of patients with parkinsonism and Wilson’s disease. Adv Neurol 24:283–292Google Scholar
  79. Nagatsu T, Wakui Y, Kato T, Fujita K, Kondo T, Yokochi F, Narabayashi H (1982) Dopamine-beta-hydroxylase activity in cerebrospinal fluid of Parkinsonian patients. Biomed Res 3:95–98Google Scholar
  80. Nelson JC, Davis JM (1997) DST studies in psychotic depression: a meta-analysis. Am J Psychiatry 154:1497–1503PubMedGoogle Scholar
  81. Ng PC, Henikoff S (2001) Predicting deleterious amino acid substitutions. Genome Res 11:863–874CrossRefPubMedGoogle Scholar
  82. O’Connor DT, Levine GL, Frigone RP (1983) Homologous radio-immunoassay of human plasma dopamine β-hydroxylase: analysis of homospecific activity, circulating plasma pool and intergroup differences based upon race, blood pressure and cardiac function. J Hypertens 1:227–233PubMedGoogle Scholar
  83. O’Connor DT, Cervenka JH, Stone RA, Levine GL, Parmer RJ, Franco-Bourland RE, Madrazo I, Langlais PJ, Robertson D, Biaggioni I (1994) Dopamine β-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic activity and variation in Parkinson’s disease and congenital dopamine β-hydroxylase deficiency. Clin Sci 86:149–158PubMedGoogle Scholar
  84. Ogihara T, Nugent CA, Shen SW, Goldfein S (1975) Serum dopamine β-hydroxylase activity in parents and children. J Lab Clin Med 85:566–570PubMedGoogle Scholar
  85. Oyarce AM, Fleming PJ (1991) Multiple forms of human dopamine β-hydroxylase in SH-SY5Y neuroblastoma cells. Arch Biochem Biophys 290:503–510PubMedGoogle Scholar
  86. Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, O’Donovan M, Owen M, Ollier W, Worthington J, Tapar A (2001) Examining for association between candidate gene polymorphisms in the dopamine pathway and attention deficit hyperactivity disorder: a family-based study. Am J Med Genet (Neuropsychiatr Genet) 105:464–470Google Scholar
  87. Peronnet F, Cleroux J, Perrault H, Thibault G, Cousineau D, de Champlain J, Guilland JC, Klepping J (1985) Plasma norepinephrine, epinephrine, and dopamine beta-hydroxylase activity during exercise in man. Med Sci Sports Exerc 17:683–688PubMedGoogle Scholar
  88. Perry SE, Summar L, Phillips JA, Robertson D (1991) Linkage analysis of the human dopamine β-hydroxylase gene. Genomics 10:493–495PubMedGoogle Scholar
  89. Pliszka SR, Rogeness GA, Medrano MA (1988) DBH, MHPG, and MAO in children with depressive, anxiety, and conduct disorders: relationship to diagnosis and symptom ratings. Psychiatry Res 24:35–44CrossRefPubMedGoogle Scholar
  90. Porter CJ, Nahmias J, Wolfe J, Craig IW (1992) Dinucleotide repeat polymorphism at the human dopamine β-hydroxylase (DBH) locus. Nucleic Acids Res 20:1429Google Scholar
  91. Province MA (2000) A single, sequential, genome-wide test to identify simultaneously all promising areas in a linkage scan. Genet Epidemiol 19:301–322CrossRefPubMedGoogle Scholar
  92. Robertson D, Goldberg MR, Hollister AS, Onrot J, Wiley R, Thompson JG, Robertson RM (1986) Isolated failure of autonomic noradrenergic neurotransmission: evidence for impaired beta-hydroxylation of dopamine. N Engl J Med 314:1494–1497PubMedGoogle Scholar
  93. Rogeness GA, Hernandez JM, Macedo CA, Mitchell EL (1982) Biochemical differences in children with conduct disorder socialized and undersocialized. Am J Psychiatry 139:307–311PubMedGoogle Scholar
  94. Rogeness GA, Hernandez JM, Macedo CA, Mitchell EL, Amrung SA, Harris WR (1984) Clinical characteristics of emotionally disturbed boys with very low activities of dopamine-beta-hydroxylase. J Am Acad Child Psychiatry 23:203–208PubMedGoogle Scholar
  95. Rogeness GA, Hernandez JM, Macedo CA, Amrung SA, Hoppe SK (1986) Near-zero plasma dopamine-beta-hydroxylase and conduct disorder in emotionally disturbed boys. J Am Acad Child Psychiatry 25:521–527PubMedGoogle Scholar
  96. Rogeness GA, Crawford L, McNamara A (1989) Plasma dopamine-beta-hydroxylase and preschool behavior in children with conduct disorder. Child Psychiatry Hum Dev 20:149–56PubMedGoogle Scholar
  97. Roman T, Schmitz M, Polanczyk GV, Eizirik M, Rohde LA, Hutz MH (2002) Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene. Am J Med Genet (Neuropsychiatric Genetics) 114:154–158Google Scholar
  98. Ross SB, Wetterberg L, Myrhead M (1973) Genetic control of plasma dopamine-β-hydroxylase. Life Sci 12:529–532CrossRefPubMedGoogle Scholar
  99. Rothschild AJ, Langlais PJ, Schatzberg AF, Walsh FX, Cole JO, Bird ED (1984) Dexamethasone increases plasma free dopamine in man. J Psychiatr Res 18:217–23PubMedGoogle Scholar
  100. Sack RL, Goodwin FK (1974) Inhibition of dopamine-β-hydroxyalse in manic patients: a clinical trial with fusaric acid. Arch Gen Psychiatry 31:649–654PubMedGoogle Scholar
  101. Sapru MK, Rao BSSR, Channabasavanna SM (1989) Serum dopamine-β-hydroxylase activity in clinical subtypes of depression. Acta Psychiatr Scand 80:474–478PubMedGoogle Scholar
  102. Satoh A, Serita T, Seto M, Tomita I, Satoh H, Iwanaga K, Takashima H, Tsujihata M (1999) Loss of 123I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 40:371–375Google Scholar
  103. Schirger A, Sheps SG, Thomas JE, Fealey RD (1981) Midodrine. A new agent in the management of idiopathic orthostatic hypotension and Shy-Drager syndrome. Mayo Clin Proc 56:429–433PubMedGoogle Scholar
  104. Singer C, Weiner WJ, Sanchez-Ramos JR (1992) Autonomic dysfunction in men with Parkinson’s disease. Eur Neurol 32:134–140PubMedGoogle Scholar
  105. Small KM, Wagoner LE, Levin AM, Kardia SLR, Liggett SB (2002) Synergistic polymorphisms of (beta) 1- and (alpha)(2C)-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 347:1135–1142Google Scholar
  106. Smith AD, de Potter WD, Moerman EJ, de Schaepdryver AF (1970) Release of dopamine-β-hydroxylase and chromogranin A upon stimulation of the splenic nerve. Tissue Cell 2:547–568Google Scholar
  107. Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52:506–516PubMedGoogle Scholar
  108. Spitzer RL, Endicott J, Robbins E (1975) Research diagnostic criteria. New York State Psychiatric Institute, Biometrics Research, New YorkGoogle Scholar
  109. Stallings MC, Corley RP, Hewitt JK, Krauter KS, Lessem JM, Mikulich SK, Rhee SH, Smolen A, Young SE, Crowley TJ (2003) A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence. Drug Alcohol Depend 70:295–307CrossRefPubMedGoogle Scholar
  110. Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, Walker K, Martinez G, Eglen RM, Whiting RL, Hegde SS (1997) Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine β-hydroxylase. Br J Pharmacol 121:1803–1809PubMedGoogle Scholar
  111. Sternberg DE, van Kammen DP, Lerner P, Bunney WE (1982) Schizophrenia: dopamine-β-hydroxylase activity and treatment response. Science 216:1423–1425PubMedGoogle Scholar
  112. Sternberg DE, van Kammen DP, Lerner P, Ballenger JC, Marder SR, Post RM, Bunney WE (1983) CSF dopamine-β-hydroxylase in schizophrenia: low activity associated with good prognosis and good response to neuroleptic treatment. Arch Gen Psychiatry 40:743–747PubMedGoogle Scholar
  113. Stewart LC, Klinman JP (1988) Dopamine beta-hydroxylase of adrenal chromaffin granules: structure and function. Annu Rev Biochem 57:551–592CrossRefPubMedGoogle Scholar
  114. Suarez GA, Opfer-Gehrking TL, Offord KP, Atkinson EJ, O’Brien PC, Low PA (1999) The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms. Neurology 52:523–528PubMedGoogle Scholar
  115. Terwilliger JD, Ott J (1992) A haplotype-based “haplotype relative risk” approach to detecting allelic associations. Hum Hered 42:337–346PubMedGoogle Scholar
  116. Tomlinson BE, Irving D, Blessed G (1981) Cell loss in the locus coeruleus in senile dementia of Alzheimer type. J Neurol Sci 49:419–428PubMedGoogle Scholar
  117. Tong ZY, Kingsbury AE, Foster OJ (2000) Up-regulation of tyrosine hydroxylase mRNA in a sub-population of A10 dopamine neurons in Parkinson’s disease. Brain Res Mol Brain Res 79:45–54CrossRefPubMedGoogle Scholar
  118. van Kammen DP, Kelley ME, Gilbertson MW, Gurklis J, O’Connor DT (1994) CSF dopamine β-hydroxylase in schizophrenia: associations with premorbid functioning and brain computerized tomography scan measures. Am J Psychiatry 151:372–378PubMedGoogle Scholar
  119. Wakabayashi K, Takahashi H (1997) Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 38:2–7Google Scholar
  120. Wei J, Ramchand CN, Hemmings GP (1997a) Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals. Hum Genet 99:52–55PubMedGoogle Scholar
  121. Wei J, Hai-Min X, Ramchand CN, Hemmings GP (1997b) Is the polymorphic microsatellite repeat of the dopamine β-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia? Biol Psychiatry 41:762–767CrossRefPubMedGoogle Scholar
  122. Weinshilboum RM (1978) Serum dopamine-β-hydroxylase. Pharmacol Rev 30:133–166PubMedGoogle Scholar
  123. Weinshilboum RM, Axelrod J (1971) Serum dopamine β-hydroxylase. Circ Res 28:307–315PubMedGoogle Scholar
  124. Weinshilboum RM, Thoa NB, Johnson DG, Kopin IJ, Axelrod J (1971) Proportional release of norepinephrine and dopamine β-hydroxylase from sympathetic nerves. Science 174:1349–1351PubMedGoogle Scholar
  125. Weinshilboum RM, Raymond FA, Elvenack LRl, Weidman WH (1973) Serum dopamine-β-hydroxylase: sibling-sibling correlation. Science 181:943–945PubMedGoogle Scholar
  126. Weinshilboum RM, Schrott HG, Raymond FA, Weidman WH, Elvevack LR (1975) Inheritance of very low serum DBH activity. Am J Hum Genet 27:573–585PubMedGoogle Scholar
  127. Wenning GK, Tison F, Ben Shlomo Y, Daniel SE, Quinn NP (1997) Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 12:133–147PubMedGoogle Scholar
  128. Wigg K, Zai G, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL, Barr CL (2002) Attention deficit hyperactivity disorder and the gene for dopamine beta-hydroxylase. Am J Psychiatry 159:1046–1048CrossRefPubMedGoogle Scholar
  129. Williams HJ, Bray N, Murphy KC, Cardno AG, Jones LA, Owen MJ (1999) No evidence for association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH). Am J Med Genet 88:557–559CrossRefPubMedGoogle Scholar
  130. Wilson AF, Elston RC, Siervogel RM, Tran LD (1988) Linkage of a gene regulating dopamine-β-hydroxylase activity and the ABO blood group locus. Am J Hum Genet 42:160–166PubMedGoogle Scholar
  131. Wilson AF, Elston RC, Sellers TA, Bailey-Wilson JE, Gerstin JM, Deen DK, Sorant AJM, Tran LD, Amos CI, Siervogel RM (1990) Stepwise oligogenic segregation and linkage analysis illustrated with dopamine-β-hydroxylase activity. Am J Med Genet 35:425–432PubMedGoogle Scholar
  132. Winer N, Carter C (1977) Effect of cold pressor stimulation on plasma norepinephrine, dopamine-β-hydroxylase, and renin activity. Life Sci 20:887–894CrossRefGoogle Scholar
  133. Wise CD, Stein L (1973) Dopamine-β-hydroxylase deficits in the brains of schizophrenic patients. Science 181:344–347PubMedGoogle Scholar
  134. Yamamoto K, Cubells JF, Gelernter J, Benkelfat C, Lalonde P, Bloom D, Lal S, Labelle A, Turecki F, Rouleau GA, Joober R (2003) Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study. Am J Med Genet Part B (Neuropsychiatr Genet) 117B:33–38CrossRefGoogle Scholar
  135. Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155:60–67CrossRefPubMedGoogle Scholar
  136. Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim C-H, Malison RT, Gelernter J, Cubells JF (2001) A quantitative trait locus analysis of human dopamine β-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68:515–522CrossRefPubMedGoogle Scholar
  137. Zabetian CP, Buxbaum SG, Elston RC, Köhnke M, Anderson GM, Gelernter J, Cubells JF (2003a) The Structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 72:1389–1400CrossRefPubMedGoogle Scholar
  138. Zabetian CP, Romero R, Robertson D, Sharma S, Padbury JF, Kuivaniemi H, Kim K-S, Kim C-H, Kohnke MD, Kranzler HR, Gelernter J, Cubells JF (2003b) A revised allele frequency estimate and haplotype analysis of the DBH deficiency mutation IVS1+2T>C in African- and European-Americans. Am J Med Genet 123A:190–192CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of PsychiatryYale University School of Medicine and VA Connecticut Health Care SystemWest HavenUSA
  2. 2.Department of NeurologyUniversity of Washington School of Medicine and VA Puget Sound Health Care SystemSeattleUSA

Personalised recommendations