| 1. |
- Arnison, Tor, Filosofie doktor, 1984-, et al.
(författare)
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Safety of and response to electroconvulsive therapy during pregnancy : Results from population‐based nationwide registries
- 2023
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Ingår i: Acta Psychiatrica Scandinavica. - : John Wiley & Sons. - 0001-690X .- 1600-0447.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited.Methods: Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score.Results: Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy.Conclusions: ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.
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| 2. |
- Bautista, D M, et al.
(författare)
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Pungent products from garlic activate the sensory ion channel TRPA1
- 2005
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:34, s. 12248-12252
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Tidskriftsartikel (refereegranskat)abstract
- Garlic belongs to the Allium family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to Allium extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.
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| 3. |
- Carli, V, et al.
(författare)
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A Naturalistic, European Multi-Center Clinical Study of Electrodermal Reactivity and Suicide Risk Among Patients With Depression
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 765128-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods:Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results:Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis.
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| 4. |
- Ekstrand, Joakim, et al.
(författare)
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Ketamine or ECT? What have we learned from the KetECT and ELEKT-D trials?
- 2024
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.
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| 5. |
- Ekstrand, Joakim, et al.
(författare)
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Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression : A Randomized, Open-Label, Non-Inferiority Trial (KetECT)
- 2022
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 25:5, s. 339-349
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression.METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session.RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52).CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.
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| 6. |
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| 7. |
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| 8. |
- Movahed Rad, Pouya
(författare)
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Endogenous activators of the pain receptor TRPV1 From cell to man
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- N-acylethanolamines (NAEs) belong to a growing family of endogenous signalling molecules acting on a variety of receptors and ion channels. In 1992, it was reported that the N-acylethanolamine anandamide is present in the brain and activates the central cannabinoid (CB) receptor. Anandamide and other NAEs are considered to be generated on demand following receptor activation or cell stress. The tissue level of anandamide increases during ischemic tissue injury and inflammation. Hydrolytic cleavage of the amide bond by fatty acid amide hydrolase is responsible for the elimination of anandamide and other N-acylethanolamines. Studies on whole animals or isolated tissues have shown that anandamide induces a variety of effects in the cardiovascular system, including vasodilatation, bradycardia and hypotension. Macrophages and monocytes, endothelial cells and sensory nerves are possible cellular sources of anandamide in the vascular system. The mechanisms behind the cardiovascular effects of anandamide are not fully understood, but seem to depend on the bioassay and the mode of administration of anandamide. In isolated arterial segments, anandamide produces vasorelaxation via activation of transient receptor potential vanilloid 1 (TRPV1) on perivascular sensory nerves and the subsequent release of the potent vasodilator calcitonin gene-related peptide. TRPV1 is a nonselective cation channel, belonging to the transient receptor potential ion channel superfamily, and the receptor for the pungent ingredient in hot chilli peppers. In this work, we show that anandamide and its metabolically stable analogue methanandamide are able to cause vasodilatation in intact vascular beds by a similar TRPV1-dependent mechanism. The vasodilator response to methanandamide in rat isolated perfused mesenteric arterial bed is inhibited by the TRPV1 antagonist ruthenium red. More importantly, anandamide together with well known plant-derived or synthetic TRPV1 agonists are able to cause vasodilatation in vivo in human skin, an effect inhibited by the selective TRPV1 antagonist capsazepine. The endogenous C18 NAEs N-linolenoylethanolamine (18:3 NAE), N-linoleoylethanolamine (18:2 NAE), N-oleoylethanolamine (18:1 NAE) and N-stearoylethanolamine (18:0 NAE) are structurally related to anandamide, but these lipids are poor ligands at cannabinoid CB1 receptors. Here we show that these lipids are present in rat sensory ganglia and vascular tissue in levels that may substantially exceed those of anandamide. 18:3 NAE, 18:2 NAE and 18:1 NAE, but not 18:0 NAE and oleic acid, activate rat TRPV1 on perivascular sensory nerves and human TRPV1 expressed in eukaryotic cells. In conclusion, this study clearly show that, in the rat isolated mesenteric arterial bed, the vasodilator response to methanandamide is mediated predominantly via activation of TRPV1 on sensory nerves. We also demonstrate for the first time that anandamide has biological activity in man, causing vasodilatation in human skin microcirculation via activation of TRPV1. We also identify novel endogenous TRPV1 ligands, belonging to the C18 NAE family of lipids. These unsaturated C18 NAEs, which are poor ligands at the cannabinoid CB1 receptor, may act in concert with anandamide as endogenous TRPV1 modulators in conditions associated with activation of capsaicin-sensitive sensory nerves, including pain, inflammation, ischemia and bladder instability.
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| 9. |
- Movahed Rad, Pouya, et al.
(författare)
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Endogenous unsaturated C18 N-acylethanolamines are vanilloid receptor (TRPV1) agonists.
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 280:46, s. 38496-38504
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Tidskriftsartikel (refereegranskat)abstract
- The endogenous C18 N-acylethanolamines (NAEs) N-linolenoylethanolamine (18:3 NAE), N-linoleoylethanolamine (18:2 NAE), N-oleoylethanolamine (18:1 NAE), and N-stearoylethanolamine (18:0 NAE) are structurally related to the endocannabinoid anandamide (20:4 NAE), but these lipids are poor ligands at cannabinoid CB1 receptors. Anandamide is also an activator of the transient receptor potential (TRP) vanilloid 1 (TRPV1) on primary sensory neurons. Here we show that C18 NAEs are present in rat sensory ganglia and vascular tissue. With the exception of 18:3 NAE in rat sensory ganglia, the levels of C18 NAEs are equal to or substantially exceed those of anandamide. At submicromolar concentrations, 18:3 NAE, 18:2 NAE, and 18:1 NAE, but not 18:0 NAE and oleic acid, activate native rTRPV1 on perivascular sensory nerves. 18:1 NAE does not activate these nerves in TRPV1 gene knock-out mice. Only the unsaturated C18 NAEs elicit whole cell currents and fluorometric calcium responses in HEK293 cells expressing hTRPV1. Molecular modeling revealed a low energy cluster of U-shaped unsaturated NAE conformers, sharing several pharmacophoric elements with capsaicin. Furthermore, one of the two major low energy conformational families of anandamide also overlaps with the cannabinoid CB1 receptor ligand HU210, which is in line with anandamide being a dual activator of TRPV1 and the cannabinoid CB1 receptor. This study shows that several endogenous non-cannabinoid NAEs, many of which are more abundant than anandamide in rat tissues, activate TRPV1 and thus may play a role as endogenous TRPV1 modulators.
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| 10. |
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| 11. |
- Movahed Rad, Pouya, et al.
(författare)
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Vascular effects of anandamide and N-acylvanillylamines in the human forearm and skin microcirculation.
- 2005
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 146:2, s. 171-179
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Tidskriftsartikel (refereegranskat)abstract
- 1 The endocannabinoid anandamide is an emerging potential signalling molecule in the cardiovascular system. Anandamide causes vasodilatation, bradycardia and hypotension in animals and has been implicated in the pathophysiology of endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not been studied in man. 2 Human forearm blood flow and skin microcirculatory flow were recorded using venous occlusion plethysmography and laser-Doppler perfusion imaging ( LDPI), respectively. Each test drug was infused into the brachial artery or applied topically on the skin followed by a standardized pin-prick to disrupt the epidermal barrier. 3 Anandamide failed to affect forearm blood flow when administered intra-arterially at infusion rates of 0.3-300 nmol min(-1). The highest infusion rate led to an anandamide concentration of approximately 1 mu M in venous blood as measured by mass spectrometry. 4 Dermal application of anandamide significantly increased skin microcirculatory flow and coapplication of the transient receptor potential vanilloid 1 ( TRPV1) antagonist capsazepine inhibited this effect. The TRPV1 agonists capsaicin, olvanil and arvanil all induced concentration-dependent increases in skin blood flow and burning pain when administered dermally. Coapplication of capsazepine inhibited blood flow and pain responses to all three TRPV1 agonists. 5 This study shows that locally applied anandamide is a vasodilator in the human skin microcirculation. The results are consistent with this lipid being an activator of TRPV1 on primary sensory nerves, but do not support a role for anandamide as a circulating vasoactive hormone in the human forearm vascular bed.
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| 12. |
- Rask, Olof, et al.
(författare)
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Electroconvulsive therapy in children and adolescents : results from a population‑based study utilising the Swedish National Quality Register
- 2023
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Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 32:11, s. 2649-2656
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Tidskriftsartikel (refereegranskat)abstract
- Electroconvulsive therapy (ECT) is effective and safe for adults with severe depression, but less studied in adolescents. Here, we examined the indications, prevalence, practice, response and remission rates, and side effects in young people treated with ECT in Sweden. We also examined the usage of ECT in the transition to adult psychiatry. Using data from national patient registers and the Swedish National Quality Register for ECT (Q-ECT), we identified patients aged up to 19 years treated with ECT over a 5-year study period. Response and remission rates were analysed using the Clinical Global Impression (7-point scale)-Improvement (CGI-I) and Severity (CGI-S). A total of 118 individuals were identified, of which 105 were also enrolled in the Q-ECT. The most common indication for ECT was depression (68%; n = 80). Adolescents aged < 18 years were more severely ill before treatment than those aged 18 years (P < 0.01). Three of the hospitals in Sweden treated the majority of adolescents < 18 years old. The median number of sessions in each ECT series was seven. Unilateral placement of the electrodes was the most common (88%; n = 99). Fifty-seven percent (n = 54) of the patients responded (CGI-I, 1-2) to the treatment; remission (CGI-S, 1-2) was achieved by 32% (n = 30). Psychotic symptoms were associated with a higher response rate in patients with depression (P = 0.038). A deterioration of memory compared to pre-treatment was reported in six patients. ECT was associated with high response and remission rates in adolescents with severe psychiatric disorders after non-response to medication.
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| 13. |
- Svensson, Maria, et al.
(författare)
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Effect of electroconvulsive seizures on pattern separation
- 2015
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Ingår i: Hippocampus. - : Wiley. - 1050-9631. ; 25:11, s. 1351-1360
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Tidskriftsartikel (refereegranskat)abstract
- Strategies employing different techniques to inhibit or stimulate neurogenesis have implicated a role for adult-born neurons in the therapeutic effect of antidepressant drugs, as well as a role in memory formation. Electroconvulsive seizures, an animal model of electroconvulsive therapy, robustly stimulate hippocampal neurogenesis but it is not known how this relates to either therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the ECS-derived increase in adult-born neurons would manifest in improved pattern separation ability, a memory function that is believed to be both hippocampus-dependent and coupled to neurogenesis. To test this hypothesis, we stimulated neurogenesis in adult rats by treating them with a series of ECS and compared their performances in a trial-unique delayed nonmatching-to-location task (TUNL) to a control group. TUNL performance was analyzed over a 12-week period, during which newly formed neurons differentiate and become functionally integrated in the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the delay between sample and choice, and by varying the spatial similarity between target and distracter location. Although animals learned the task and improved the number of correct responses over time, ECS did not influence spatial pattern separation ability.
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| 14. |
- Ygland Rödström, Maria, et al.
(författare)
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Acute Mania and Catatonia in a Teenager Successfully Treated with Electroconvulsive Therapy and Diagnosed with Turner Syndrome and Bipolar Disorder
- 2021
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Ingår i: Case Reports in Psychiatry. - : Hindawi Limited. - 2090-682X .- 2090-6838. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background. Turner syndrome (TS) is an X-linked chromosomal abnormality with a global prevalence of 1/2000 live-born girls. The physiological symptoms of TS have been thoroughly characterized, but only a few studies have described associated psychiatric symptoms. We report a case of an adolescent girl who presented with acute mania with psychotic features and was successfully treated with electroconvulsive therapy (ECT). She was subsequently diagnosed with bipolar syndrome and TS. Case Presentation. A 17-year-old girl presented to us with manic symptoms, including disorganized speech, auditory hallucinations, and affect lability. Initially, she was treated with antipsychotics and benzodiazepines, whereby the positive affective symptoms declined. However, the psychotic symptoms progressed, and she developed a catatonic state. ECT was started 6 days after admission, with improvement after two treatments. When ECT was tapered after seven sessions, she relapsed, and the treatment was extended to twelve sessions, with successful outcome. Following discharge, she was diagnosed with TS with partial loss on one of the X-chromosomes (46X, del (X)(p21)), which might have contributed to the development of her sudden acute manic episode. Conclusions. This case demonstrates for the first time that ECT may be a safe and efficient treatment strategy for acute mania in adolescents with concomitant TS and that severely affected adolescents may require a prolonged series with gradual tapering of ECT. The present case also demonstrates a possible association between TS and bipolar syndrome and that the clinical presentation of a manic episode in a patient with this comorbidity could be more complex and the treatment response slower.
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| 15. |
- Zygmunt, Peter, et al.
(författare)
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Monoacylglycerols Activate TRPV1 - A Link between Phospholipase C and TRPV1.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches. The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric arteries from TRPV1 knock-out mice, vasodilator responses to 2-arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands of phospholipase C-coupled membrane receptors, increased the content of 2-arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the phospholipase C-coupled histamine H1 receptor, exposure to histamine stimulated the formation of 2-AG, and this effect was augmented in the presence of JZL184. These effects were prevented by the diacylglycerol lipase inhibitor tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells co-expressing TRPV1 and the histamine H1 receptor, and the TRPV1 antagonist capsazepine abolished these currents. JZL184 increased the histamine-induced currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor ciclosporin and the endogenous "entourage" compound palmitoylethanolamide potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1 activation of this monoacylglycerol at nanomolar concentrations. Furthermore, intracerebroventricular injection of JZL184 produced TRPV1-dependent antinociception in the mouse formalin test. Our results show that intact 2-arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators, contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1-mediated antinociceptive signaling in the brain.
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