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| 2. |
- Backlund, Lena, et al.
(författare)
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Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
- 2011
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 13:5-6, s. 500-8
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.
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| 3. |
- Backlund, L., et al.
(författare)
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P2RX7: Expression Responds to Sleep Deprivation and Associates with Rapid Cycling in Bipolar Disorder Type 1
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- Context: Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling. Objectives: To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients. Design: Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients. Participants: Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044). Results: P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912_A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls. Conclusions: Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system.
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| 4. |
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| 5. |
- Erhardt, Sophie, et al.
(författare)
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Connecting Inflammation with Glutamate Agonism in Suicidality
- 2013
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:5, s. 743-752
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Tidskriftsartikel (refereegranskat)abstract
- The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (Pandlt;0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. Neuropsychopharmacology (2013) 38, 743-752; doi:10.1038/npp.2012.248; published online 9 January 2013
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| 6. |
- Hallberg, Ludvig, et al.
(författare)
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Decreased aldosterone in the plasma of suicide attempters with major depressive disorder.
- 2011
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 187, s. 135-139
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Tidskriftsartikel (refereegranskat)abstract
- Hormones and neurobiological factors may be regulated differently in suicidal versus non-suicidal depressive patients. There is currently limited knowledge about the relation of substances in the Renin-Angiotensin-Aldosterone system to depression and suicidality. We therefore investigated whether plasma levels of renin and aldosterone differ between suicide attempters, non-suicidal depressive patients and healthy controls. Furthermore, we analyzed the relation of renin and aldosterone to psychiatric symptoms in the patients. Suicidal patients with MDD, adjustment disorder and dysthymia, as well as two control groups consisting of non-suicidal MDD patients and healthy subjects, were rated using the Comprehensive Psychopathological Rating Scale (CPRS), including the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Plasma samples were frozen immediately after collection and stored at -80 degrees C for 5-18years. Aldosterone and renin levels were analyzed using radioactive- and chemiluminescent immunoassays. We found that suicide attempters with MDD had significantly lower plasma levels of aldosterone than the other patient groups, as well as than the healthy controls. Moreover, increasing severity of psychiatric symptoms was associated with lower aldosterone levels in the suicide attempters with MDD. Non-suicidal patients with MDD did not differ significantly compared to healthy controls with respect to aldosterone and renin levels. These findings may indicate that low aldosterone levels could be a marker of suicidality in patients with MDD.
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| 7. |
- Holländare, Fredrik, 1972-
(författare)
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Managing depression via the Internet : self-report measures, treatment & relapse prevention
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cognitive behaviour therapy (CBT) is an effective treatment for depression but access is limited. One way of increasing access is to offer CBT via the Internet. In Study I, guided Internet-based CBT was found to have a large effect on depressive symptoms compared to taking part in an online discussion group. Approximately two hours were spent on guiding each patient and the large effect found differs from previous studies that showed smaller effects, probably due to lack of guidance. The intervention had no effect on the participants’ quality of life but significantly decreased their level of anxiety. Internet-based versions of self-report measures can be more practical and efficient than paper versions. However, before implementation, evidence of psychometrical equivalence to the paper versions should be available. This was tested in Studies II and III for the Montgomery-Åsberg Depression Rating Scale – Self-rated (MADRS-S) and the Beck Depression Inventory – Second Edition (BDI-II). When the full scales were investigated, equivalent psychometric properties were found in the two versions of the MADRS-S and BDI-II. However, in the Internet-version of the BDI-II, a lower score was found for the question about suicidality and the difference was statistically significant. Although the difference was small, this indicates that suicidality might be underestimated when using the Internet-based BDI-II. As the long-term prognosis after treatment for depression is poor, in Study IV we investigated the possibility of delivering CBT-based relapse prevention via the Internet. The results revealed that fewer participants in the intervention group experienced a relapse compared to the control group and that the time spent on guiding each participant was approximately 2.5 hours. A trend towards a higher remission rate was found in the CBT group at the six-month follow-up and a reduction of depressive symptoms was associated with a lowered risk of relapse. CBT-based relapse prevention via the Internet can potentially be made available to large numbers of patients, thus improving their prognosis. The Internet increases the possibilities for health care providers in the management of depression.
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| 8. |
- Hukic, Dzana Sudic, et al.
(författare)
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Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.Methodology:Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. Results: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. Conclusion:Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population. © 2013 Hukic et al.
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| 9. |
- Janelidze, Shorena, et al.
(författare)
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Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 38:6, s. 853-862
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines constitute a class of small inflammatory proteins that control the chemotaxis of leukocytes. They are also present in the central nervous system (CNS) and contribute to diverse physiological functions, such as the regulation of cell migration, axonal growth and neuronal survival. It is to date not known whether chemokines in the CNS are affected in psychiatric disorders. In this study, chemokine levels were measured in the cerebrospinal fluid (CSF) of 137 psychiatric patients in conjunction to a suicide attempt, and 43 healthy controls. A subgroup of patients (n = 42) was followed up with blood samples 12 years after the initial CSF collection, when they did not show suicidal behavior. The follow-up chemokine levels were compared to those of psychiatric patients (n = 17) who had never attempted suicide. Ultrasensitive chemokine multiplex immunoassay was used to quantify eotaxin-1 (CCL11), interferon gamma-induced protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1 beta (MIP-1 beta, CCL4), monocyte chemotactic protein-1 (MCP-1, CCL2), MCP-4 (CCL13) and thymus and activation regulated chemokine (TARC, CCL17). Patients were diagnosed using DSM-III-R/DSM-IV, and assessed using the Comprehensive Psychopathological Rating Scale (CPRS), including subscales, and the Suicidal Intent Scale (SIS). CSF eotaxin-1, MIP-1 beta, MCP-1, MCP-4 and TARC were significantly lower in suicide attempters than in healthy controls. Low chemokine levels were specifically associated with psychotic symptoms and pain. In the samples collected at follow-up, TARC was significantly lower in suicide attempters compared to psychiatric patients who had never attempted suicide. We also found a positive correlation between blood TARC and brain-derived neurotrophic factor (BDNF) levels. Our study thus provides evidence of reduced chemokine levels in suicide attempters, both in the acute suicidal setting, and at long-term, compared to non-attempters. These results warrant future studies on the detailed neurobiological functions of chemokines in psychiatric patients. (C) 2012 Elsevier Ltd. All rights reserved.
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| 10. |
- Janelidze, Shorena, et al.
(författare)
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Cytokine levels in the blood may distinguish suicide attempters from depressed patients.
- 2011
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Ingår i: Brain, Behavior, and Immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 25, s. 335-339
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Tidskriftsartikel (refereegranskat)abstract
- Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressive patients, as well as healthy controls. Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS). We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication. These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.
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