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- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 2. |
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| 3. |
- Schwieler, L., et al.
(författare)
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Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients
- 2016
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. Methods: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). Results: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P < 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P < 0.0001) as well as a significantly increased QUIN/KYNA ratio (P < 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P < 0.05), kynurenine (P < 0.01), and QUIN (P < 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P < 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). Conclusions: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.
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