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Polymorphisms in AKR1C4 and HSD3B2 and differences in serum DHEAS and progesterone are associated with paranoid ideation during mania or hypomania in bipolar disorder

Johansson, A. G. M. (författare)
Nikamo, P. (författare)
Schalling, M. (författare)
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Landén, Mikael, 1966- (författare)
Göteborgs universitet, Institutionen för neurovetenskap och fysiologi, Gothenburg University, Institute of Neuroscience and Physiology
Landen, M, (författare)
Karolinska Institutet
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Göteborgs universitet Sahlgrenska akademin. Institutionen för neurovetenskap och fysiologi. 
2012
Engelska.
Ingår i: European Neuropsychopharmacology. - 0924-977X. ; 22:9, s. 632-640
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Paranoia is commonly a mood-incongruent psychotic symptom of mania which may be related to dopamine dysregulation. Progesterone and its metabolite allopregnanolone (ALLO) have been found in animals to antagonize the effects of dopamine. We therefore examined serum progesterone, its endogenous antagonist DHEAS and polymorphisms of the genes coding for certain steroidogenetic enzymes (AKR1C4, HSD3B2, and SRD5A1) in 64 males and 96 females with bipolar 1 or 2 disorder with or without paranoid ideation during mood elevation. Euthymic morning serum progesterone, DHEAS and cortisol concentrations were measured in males and in premenopausal women who were in follicular phase and not taking oral contraceptives. In women only, SNPs in AKR1C4 reduced the likelihood of having exhibited paranoid ideation by circa 60%. The haplotype of all 4 SNPs in the AKR1C4 gene reduced the risk of exhibiting paranoia by 80% (OR 0.19, 95% CI 0.06-0.61, p=0.05). A history of paranoid ideation was not, however, related to progesterone or DHEAS concentration. Serum DHEAS and progesterone concentrations were lower in men who had shown paranoid ideation during mania/hypomania compared with those who had not (F=7.30, p = 0.006) however this was not coupled to polymorphisms in the selected genes. The ancestral G in rs4659174 in HSD3B2 was in men associated with a lower risk of paranoid ideation (likelihood ratio chi(2) 3.97, p = 0.046, OR 0.31 (95% CI 0.10-0.96)) but did not correlate with hormone concentrations. Hence, gene variants in the steroidogenetic pathway and steroids concentration differences may be involved in the susceptibility to paranoia during mood elevation. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Bipolar disorder
Progesterone
DHEAS
AKR1C4
Paranoia
Persecutory delusions
HSD3B
SRD5A1
beta-hydroxylase gene
dehydroepiandrosterone-sulfate
3-alpha-hydroxysteroid dehydrogenases
5-alpha-reductase type-1
major
depression
prostate-cancer
ngfi-b
dopamine
metabolism
schizophrenia

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