| 11. |
- Goes, Fernando S, et al.
(author)
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Exome Sequencing of Familial Bipolar Disorder.
- 2016
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 590-7
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Journal article (peer-reviewed)abstract
- Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.
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| 12. |
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| 13. |
- Song, J., et al.
(author)
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Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder
- 2016
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:9, s. 1290-1297
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Journal article (peer-reviewed)abstract
- Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P = 2.74 x 10(-8)). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.
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| 14. |
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| 15. |
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| 16. |
- Brundin, L., et al.
(author)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Journal article (peer-reviewed)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 17. |
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| 18. |
- Falla, D., et al.
(author)
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Perceived pain extent is associated with disability, depression and self-efficacy in individuals with whiplash-associated disorders
- 2016
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In: European Journal of Pain. - : WILEY-BLACKWELL. - 1090-3801 .- 1532-2149. ; 20:9, s. 1490-1501
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Journal article (peer-reviewed)abstract
- BackgroundCompletion of a pain drawing is a familiar task in those presenting with whiplash-associated disorders (WAD). Some people report pain almost over their entire body. Yet the reasons for larger pain extent have not been fully explored. MethodsA novel method was applied to quantify pain extent from the pain drawings of 205 individuals with chronic WAD. Pain extent was evaluated in relation to sex, age, educational level, insurance status and financial status. Multiple linear regression analysis was used to verify whether pain extent was associated with other health indicators including perceived pain and disability, health-related quality of life, pain catastrophizing, anxiety, depression and self-efficacy. ResultsPain extent was influenced by sex ((2):10.392, pamp;lt;0.001) with larger pain extent in women compared to men (7.887.66% vs. 5.406.44%). People with unsettled insurance claims ((2): 7.500, pamp;lt;0.05) and those with a worse financial situation ((2):12.223, pamp;lt;0.01) also had larger pain extent. Multiple linear regression models revealed that, when accounting for age, sex, education, insurance status, financial status and neck pain intensity, pain extent remained associated with perceived disability (pamp;lt;0.01), depression (pamp;lt;0.05) and self-efficacy (pamp;lt;0.001). ConclusionBy utilizing a novel method for pain extent quantification, this study shows that widespread pain is associated with a number of factors including perceived disability, depression and self-efficacy in individuals with chronic WAD. Widespread pain should alert the clinician to consider more specific psychological screening, particularly for depression and self-efficacy, in patients with WAD. What does this study add?Women with chronic WAD, those with unsettled insurance claims and those with poorer financial status perceive more widespread pain. When controlling for these factors, larger pain areas remain associated with perceived pain and disability, depression and self-efficacy. The pain drawing is useful to support psychological screening in people with chronic WAD.
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| 19. |
- Hughes, Timothy, et al.
(author)
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A Loss-of-Function Variant in a Minor Isoform of ANK3 Protects Against Bipolar Disorder and Schizophrenia.
- 2016
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In: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 80:4, s. 323-330
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Journal article (peer-reviewed)abstract
- Ankyrin-3 (ANK3) was one of the first genes to reach significance in a bipolar disorder genome-wide association study. Many subsequent association studies confirmed this finding and implicated this gene in schizophrenia. However, the exact nature of the role of ANK3 in the pathophysiology remains elusive. In particular, the specific isoforms involved and the nature of the imbalance are unknown.
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| 20. |
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