Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression

Meyers, Barnett S.; Alexopoulos, George S.; Kakuma, Tatsu; Tirumalasetti, Fughik; Gabriele, Michelle; Alpert, Stephanie; Bowden, Charles L.; Meltzer, Herbert Y.

doi:10.1016/s0006-3223(98)00085-7

Cited by 47 publications

(35 citation statements)

References 14 publications

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“…29 Thus, variation at DBH that causes lower plasma D␤H levels will also be expressed within noradrenergic and adrenergic neurons. The present results, combined with previous observations at the biochemical level, [23][24][25][26][27][28] therefore suggest that variation at the DBH locus can modify individual vulnerability to drug-induced and idiopathic psychotic symptoms by modifying noradrenergic and/or adrenergic neuronal phenotypes.…”

Section: A Dbh Haplotypic Association To Cocaine-induced Paranoiasupporting

confidence: 83%

“…23,24 In unipolar depression, several studies have found significantly lower serum D␤H levels in patients with unipolar major depression with psychotic features, compared to those without psychotic features. [25][26][27][28] Current study We previously showed that a silent single nucleotide polymorphism at the 3Ј end of DBH exon 2, DBH* 444g/a, comprised of either guanidine (g) or adenine (a) at cDNA nucleotide position 444 29 associated with plasma and CSF D␤H in European-Americans (EA). 22 The a-containing allele, DBH*444a, associates with low D␤H levels, while the g-containing allele, DBH* 444g, associates with higher D␤H levels.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

“…In the present study, strong association between DBH alleles and plasma D␤H levels (references 21, 22, and present data), anchored in prior linkage data, 19,20 allowed us to use plasma D␤H phenotypes to guide construction of a specific 'one-tailed' hypothesis. Thus, prior associations of low D␤H levels to psychotic symptoms [23][24][25][26][27][28] strongly suggested that a specific low-D␤H associated haplotype, Del-a, would associate with greater vulnerability to cocaine-induced paranoia. Consistent with this hypothesis, Del-a was significantly more frequent in P(+) cocaine-dependent subjects as compared to P(−) cocaine-dependent subjects.…”

Section: A Dbh Haplotypic Association To Cocaine-induced Paranoiamentioning

confidence: 99%

“…[25][26][27][28] Two of those studies were performed in predominantly EA populations, 25,28 one in an Eastern European population, 26 and one in a subcontinental Asian population. 27 …”

Section: Limitationsmentioning

confidence: 99%

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A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

et al. 2000

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Low levels of dopamine ␤-hydroxylase (D␤H) protein in the plasma or cerebrospinal fluid (CSF) are associated with greater vulnerability to positive psychotic symptoms in several psychiatric disorders. D␤H level is a stable, genetically controlled trait. DBH, the locus encoding D␤H protein, is the major quantitative trait locus controlling plasma and CSF D␤H levels. We therefore hypothesized that DBH variants or haplotypes, associated with low levels of D␤H in the plasma, would also associate with greater vulnerability to cocaine-induced paranoia. To test this hypothesis, we first showed that a di-allelic variant, DBH*5Ј-ins/del, located approximately 3 kb 5Ј to the DBH transcriptional start site, significantly associates with plasma D␤H activity in European-Americans (n = 66). Linkage disequilibrium analysis of that polymorphism and DBH*444g/a, another di-allelic variant associated with D␤H levels, demonstrated that alleles of similar association to D␤H levels are in positive disequilibrium. We then estimated DBH haplotype frequencies in cocaine-dependent European Americans rated for cocaine-induced paranoia (n = 45). As predicted, the low-D␤H-associated haplotype, Del-a, was significantly more frequent (P = 0.0003) in subjects endorsing cocaine-induced paranoia (n = 29) than in those denying it (n = 16). Comparison to control haplotype frequencies (n = 145 healthy European-Americans) showed that the association predominantly reflected under-representation of Del-a haplotypes in those denying cocaine-induced paranoia. We conclude that: (a) the two DBH polymorphisms we studied are associated with plasma DBH levels; (b) those two polymorphisms are in significant linkage disequilibrium in European Americans, with alleles of similar association to D␤H levels in positive disequilibrium; and (c) the haplotype associated with low DBH activity is also associated with cocaine-induced paranoia. Molecular Psychiatry (2000) 5, 56-63.Keywords: psychotic disorders; substance-related disorders; central nervous system stimulants; norepinephrine; catecholamines; schizophrenia; alleles; genes More than 60% of experienced cocaine users report paranoia during cocaine intoxication, while the remainder deny even mild cocaine-induced paranoia (CIP), despite reporting similar routes of administration, duration of cocaine dependence, and lifetime and per-binge quantities of cocaine ingested. 1-3 Satel and Edell 4 reported elevated scores on a measure of psychosis proneness in cocaine-dependent subjects who endorsed CIP compared to those who did not. These data suggest the presence of substantial interindividual variation in vulnerability to CIP. Evidence for genetic influences on vulnerability to drug-induced paranoiaSeveral lines of evidence support genetic factors as modulators of individual vulnerability to CIP. Numerous animal studies support the importance of genetic factors in behavioral responses to cocaine. 5 Abstinent human cocaine users who endorse CIP exhibit deficits in P50 sensory gating of auditory stimuli, 6 a heritable p...

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Section: A Dbh Haplotypic Association To Cocaine-induced Paranoiasupporting

confidence: 83%

Section: Molecular Psychiatrymentioning

confidence: 99%

Section: A Dbh Haplotypic Association To Cocaine-induced Paranoiamentioning

confidence: 99%

“…[25][26][27][28] Two of those studies were performed in predominantly EA populations, 25,28 one in an Eastern European population, 26 and one in a subcontinental Asian population. 27 …”

Section: Limitationsmentioning

confidence: 99%

See 2 more Smart Citations

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

et al. 2000

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“…Several polymorphisms, including rs1989787 (−2073C/T) [2], rs161115 (−970C/T; previously called −1021C/T) [1,10,28], rs1108580 (444 * G/A) [5], rs1611125 (IVS4+601T/C) [28], and rs6271 (1603C/T) [21,28], were found to have significant correlations with DBH activity and levels in plasma and cerebrospinal fluid. Numerous studies have implicated low DBH activity as a risk factor for psychotic symptoms in several psychiatric disorders, such as schizophrenia, psychotic depression, and substance-induced psychosis [3,4,8,12,13,14,16,26,27]. In addition, rs5320 (Ala211Thr), a non-synonymous variant of the DBH gene, has recently been revealed to influence nicotine dependence in a Japanese population [6].…”

Section: Introductionmentioning

confidence: 99%

Association Study of Dopamine β-Hydroxylase Gene with Methamphetamine Psychosis

Okahisa¹,

Ujike²,

Takaki³

et al. 2014

Journal of Drug and Alcohol Research

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Dopamine is a key molecule in the pathophysiology of methamphetamine (METH) psychosis. We examined the association between METH psychosis and the dopamine β-hydroxylase (DBH) gene, which modulates dopaminergic cascades. Six polymorphisms, rs1989787, rs1611115, rs1108580, rs5320, rs1611125, and rs6271, of the DBH gene were genotyped. These polymorphisms were not associated with METH-seeking behaviors of patients with METH psychosis (N = 216) or healthy controls (N = 328), but rs1611125 affected one of the clinical phenotypes of METH psychosis. Individuals with the G/G homozygote of rs1611125 had a significant risk for spontaneous relapse of METH psychosis (P = .02, odds ratio = 2.2). In haplotype analyses, rs1108580-rs5320-rs1611125 was revealed to be associated with METH psychosis (P = .01). Having G-Ala-G was a significant risk factor, while A-Thr-A was a protective factor for METH psychosis (odds ratio were 9.9 and 0.16, resp.). Our present findings indicated that the DBH gene may play an important role in METH psychosis.

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Genetic Approaches to Depression: Association Studies

Tandon¹,

Aitchison²

2005

Biology of Depression

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Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression

Cited by 47 publications

References 14 publications

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

Association Study of Dopamine β-Hydroxylase Gene with Methamphetamine Psychosis

Genetic Approaches to Depression: Association Studies

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