| 1. |
- 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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| 2. |
- Brundin, L., et al.
(författare)
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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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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Brus, Ole, 1982-, et al.
(författare)
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Self-assessed remission rates after electroconvulsive therapy of depressive disorders
- 2017
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Ingår i: European Psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 45, s. 154-160
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Tidskriftsartikel (refereegranskat)abstract
- Background Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting. Methods Depressed patients who underwent ECT in 2011–2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0–10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics. Results Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus ≥ 0.50 ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission. Conclusions This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication. © 2017 The Author(s)
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| 4. |
- Falla, D., et al.
(författare)
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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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Ingår i: European Journal of Pain. - : WILEY-BLACKWELL. - 1090-3801 .- 1532-2149. ; 20:9, s. 1490-1501
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Karanti, Alina (Aikaterini), et al.
(författare)
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Gender differences in the treatment of patients with bipolar disorder: A study of 7354 patients
- 2015
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 174, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gender differences in treatment that are not supported by empirical evidence have been reported in several areas of medicine. Here, the aim was to evaluate potential gender differences in the treatment for bipolar disorder. Methods: Data was collected from the Swedish National Quality Assurance Register for bipolar disorder (BipolaR). Baseline registrations from the period 2004-2011 of 7354 patients were analyzed. Multiple logistic regression analysis was used to study the impact of gender on interventions. Results: Women were more often treated with antidepressants, lamotrigine, electroconvulsive therapy, benzodiazepines, and psychotherapy. Men were more often treated with lithium. There were no gender differences in treatment with mood stabilizers as a group, neuroleptics, or valproate. Subgroup analyses revealed that ECT was more common in women only in the bipolar l subgroup. Contrariwise, lamotrigine was more common in women only in the bipolar II subgroup. Limitations: As BipolaR contains data on outpatient treatment of persons with bipolar disorder in Sweden, it is unclear if these Findings translate to inpatient care and to outpatient treatment in other countries. Conclusions: Men and women with bipolar disorder receive different treatments in routine clinical settings in Sweden. Gender differences in level of functioning, bipolar subtype, or severity of bipolar disorder could not explain the higher prevalence of pharmacological treatment, electroconvulsive therapy, and psychotherapy in women. Our results suggest that clinicians' treatment decisions are to some extent unduly influenced by patients' gender. (C) 2014 Elsevier B.V. All rights reserved.
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| 7. |
- Peterson, Gunnel, et al.
(författare)
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THE EFFECT OF 3 DIFFERENT EXERCISE APPROACHES ON NECK MUSCLE ENDURANCE, KINESIOPHOBIA, EXERCISE COMPLIANCE, AND PATIENT SATISFACTION IN CHRONIC WHIPLASH
- 2015
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Ingår i: Journal of Manipulative and Physiological Therapeutics. - : MOSBY-ELSEVIER. - 0161-4754 .- 1532-6586. ; 38:7, s. 465-746.e4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to compare the effects of 3 different exercise approaches on neck muscle endurance (NME), kinesiophobia, exercise compliance, and patient satisfaction in patients with chronic whiplash. Methods: This prospective randomized clinical trial included 216 individuals with chronic whiplash. Participants were randomized to 1 of 3 exercise interventions: neck-specific exercise (NSE), NSE combined with a behavioral approach (NSEB), or prescribed physical activity (PPA). Measures of ventral and dorsal NME (endurance time in seconds), perceived pain after NME testing, kinesiophobia, exercise compliance, and patient satisfaction were recorded at baseline and at the 3- and 6-month follow-ups. Results: Compared with individuals in the prescribed physical activity group, participants in the NSE and NSEB groups exhibited greater gains in dorsal NME (P = .003), greater reductions in pain after NME testing (P = .03), and more satisfaction with treatment (P less than .001). Kinesiophobia and exercise compliance did not significantly differ between groups (P greater than .07). Conclusion: Among patients with chronic whiplash, a neck-specific exercise intervention (with or without a behavioral approach) appears to improve NME. Participants were more satisfied with intervention including neck-specific exercises than with the prescription of general exercise.
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