, Volume 174, Issue 4, pp 463–476

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




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.


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.


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.


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.


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.


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


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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

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