المؤلفون: Leila Marie Frid, Ute Kessler, Olga Therese Ousdal, Åsa Hammar, Jan Haavik, Frank Riemer, Marco Hirnstein, Lars Ersland, Vera Jane Erchinger, Eivind Haga Ronold, Gyrid Nygaard, Petter Jakobsen, Alexander R. Craven, Berge Osnes, Renata Alisauskiene, Hauke Bartsch, Stephanie Le Hellard, Anne-Kristin Stavrum, Ketil J. Oedegaard, Leif Oltedal

المصدر: BMC Psychiatry, Vol 23, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: Electroconvulsive therapy, Magnetic resonance imaging, Transcranial magnetic stimulation, Major depressive disorder, Cognitive deficits, Psychiatry, RC435-571

الوصف: Abstract Background Noninvasive neurostimulation treatments are increasingly being used to treat major depression, which is a common cause of disability worldwide. While electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are both effective in treating depressive episodes, their mechanisms of action are, however, not completely understood. ECT is given under general anesthesia, where an electrical pulse is administered through electrodes placed on the patient’s head to trigger a seizure. ECT is used for the most severe cases of depression and is usually not prescribed before other options have failed. With TMS, brain stimulation is achieved through rapidly changing magnetic fields that induce electric currents underneath a ferromagnetic coil. Its efficacy in depressive episodes has been well documented. This project aims to identify the neurobiological underpinnings of both the effects and side effects of the neurostimulation techniques ECT and TMS. Methods The study will utilize a pre-post case control longitudinal design. The sample will consist of 150 subjects: 100 patients (bipolar and major depressive disorder) who are treated with either ECT (N = 50) or TMS (N = 50) and matched healthy controls (N = 50) not receiving any treatment. All participants will undergo multimodal magnetic resonance imaging (MRI) as well as neuropsychological and clinical assessments at multiple time points before, during and after treatment. Arterial spin labeling MRI at baseline will be used to test whether brain perfusion can predict outcomes. Signs of brain disruption, potentiation and rewiring will be explored with resting-state functional MRI, magnetic resonance spectroscopy and multishell diffusion weighted imaging (DWI). Clinical outcome will be measured by clinician assessed and patient reported outcome measures. Memory-related side effects will be investigated, and specific tests of spatial navigation to test hippocampal function will be administered both before and after treatment. Blood samples will be stored in a biobank for future analyses. The observation time is 6 months. Data will be explored in light of the recently proposed disrupt, potentiate and rewire (DPR) hypothesis. Discussion The study will contribute data and novel analyses important for our understanding of neurostimulation as well as for the development of enhanced and more personalized treatment. Trial registration ClinicalTrials.gov Identifier: NCT05135897.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-244XTest

الوصول الحر: https://doaj.org/article/1505209c9ea640909735dc1347a4324eTest

المؤلفون: Freek ten Doesschate, Willem Bruin, Peter Zeidman, Christopher C. Abbott, Miklos Argyelan, Annemieke Dols, Louise Emsell, Philip F.P. van Eijndhoven, Eric van Exel, Peter C.R. Mulders, Katherine Narr, Indira Tendolkar, Didi Rhebergen, Pascal Sienaert, Mathieu Vandenbulcke, Joey Verdijk, Mike van Verseveld, Hauke Bartsch, Leif Oltedal, Jeroen A. van Waarde, Guido A. van Wingen

المصدر: Brain Stimulation, Vol 16, Iss 4, Pp 1128-1134 (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. Objective: We investigated whether there are consistent changes in effective resting-state connectivity. Methods: This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. Results: Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. Conclusions: A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23018697Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/35287121bdbc484b93099625711a1b7aTest

المؤلفون: Vera J. Erchinger, Alexander R. Craven, Lars Ersland, Ketil J. Oedegaard, Christoffer A. Bartz-Johannessen, Åsa Hammar, Jan Haavik, Frank Riemer, Ute Kessler, Leif Oltedal

المصدر: Frontiers in Psychiatry, Vol 14 (2023)

مصطلحات موضوعية: depression, electroconvulsive therapy, 1H-MRS nuclear magnetic resonance spectroscopy, neurometabolites, choline, myoinositol, Psychiatry, RC435-571

الوصف: IntroductionBased on previous research on electroconvulsive therapy (ECT) we have proposed a model where disruption, potentiation, and rewiring of brain networks occur in sequence and serve as the underlying therapeutic mechanism of ECT. This model implies that a temporary disturbance of neuronal networks (disruption) is followed by a trophic effect (potentiation), which enables the rewiring of neuronal circuits to a more euthymic functioning brain. We hypothesized that disruption of neuronal networks could trigger biochemical alterations leading to a temporary decrease in N-acetylaspartate (tNAA, considered a marker of neuronal integrity), while choline (a membrane component), myo-Inositol (mI, astroglia marker), and glutamate/glutamine (Glx, excitatory neurotransmitter) were postulated to increase. Previous magnetic resonance spectroscopy studies, reporting diverse findings, have used two different referencing methods - creatine ratios and tissue corrected values referenced to water – for the quantification of brain metabolites. Changes in creatine during ECT have also been reported, which may confound estimates adopting this as an internal reference.MethodsUsing MR spectroscopy, we investigated 31 moderately to severely depressed patients and 19 healthy controls before, during, and after ECT or at similar time points (for controls). We tested whether biochemical alterations in tNAA, choline, mI, and Glx lend support to the disrupt, potentiate, and rewire hypothesis. We used both creatine ratios and water-scaled values for the quantification of brain metabolites to validate the results across referencing methods.ResultsLevels of tNAA in the anterior cingulate cortex decreased after an ECT treatment series (average 10.6 sessions) by 6% (p = 0.007, creatine ratio) and 3% (p = 0.02, water referenced) but returned to baseline 6 months after ECT. Compared to after treatment series tNAA levels at 6-month follow-up had increased in both creatine ratio (+6%, p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1155689/fullTest; https://doaj.org/toc/1664-0640Test

الوصول الحر: https://doaj.org/article/eb3616d0646044b8b890459b5b26bc8eTest

المؤلفون: Laurens van de Mortel, Willem Bruin, Rajat Thomas, Chris Abbott, Miklos Argyelan, Philip van Eijndhoven, Peter Mulders, Katherine Narr, Indira Tendolkar, Joey Verdijk, Jeroen van Waarde, Hauke Bartsch, Leif Oltedal, Guido van Wingen

المصدر: Brain Stimulation, Vol 16, Iss 1, Pp 129- (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23000529Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/5eae52902ce14712b3cc1980eb9a379eTest

المؤلفون: Joey Verdijk, Freek Ten Doesschate, Laurens van de Mortel, Joshua Lukemire, Julia Pottkämper, Jeannette Hofmeijer, Leif Oltedal, Guido van Wingen, Jeroen van Waarde

المصدر: Brain Stimulation, Vol 16, Iss 1, Pp 129- (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23000530Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/9733a5ca655d4f8b9684c704bda53c27Test

المؤلفون: Giulio Emilio Brancati, Njål Brekke, Hauke Bartsch, Ole Johan Evjenth Sørhaug, Olga Therese Ousdal, Åsa Hammar, Peter Moritz Schuster, Ketil Joachim Oedegaard, Ute Kessler, Leif Oltedal

المصدر: Brain Stimulation, Vol 14, Iss 5, Pp 1330-1339 (2021)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Background: Electroconvulsive therapy (ECT) has been shown to induce broadly distributed cortical and subcortical volume increases, more prominently in the amygdala and the hippocampus. Structural changes after one ECT session and in the long-term have been understudied. Objective: The aim of this study was to describe short-term and long-term volume changes induced in cortical and subcortical regions by ECT. Methods: Structural brain data were acquired from depressed patients before and 2 h after their first ECT session, 7–14 days after the end of the ECT series and at 6 months follow up (N = 34). Healthy, age and gender matched volunteers were scanned according to the same schedule (N = 18) and patients affected by atrial fibrillation were scanned 1–2 h before and after undergoing electrical cardioversion (N = 16). Images were parcelled using FreeSurfer and estimates of cortical gray matter volume and subcortical volume changes were obtained using Quarc. Results: Volume increase was observable in most of gray matter regions after 2 h from the first ECT session, with significant results in brain stem, bilateral hippocampi, right putamen and left thalamus, temporal and occipital regions in the right hemisphere. At the end of treatment series, widespread significant volume changes were observed. After six months, the right amygdala volume was still significantly increased. No significant changes were observed in the comparison groups. Conclusions: Volume increases in gray matter areas can be detected 2 h after a single ECT session. Further studies are warranted to explore the underlying molecular mechanisms.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X21002205Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/c5e4cc2841d940b1b77fc61b0094034cTest

المؤلفون: Mohummad A. Rahman, Jorunn Brekke, Victoria Arnesen, Marianne H. Hannisdal, Andrea G. Navarro, Andreas Waha, Lars Herfindal, Cecilie B. Rygh, Eirik Bratland, Petter Brandal, Judit Haasz, Leif Oltedal, Hrvoje Miletic, Arvid Lundervold, Stein A. Lie, Dorota Goplen, Martha Chekenya

المصدر: Immunity, Inflammation and Disease, Vol 8, Iss 3, Pp 342-359 (2020)

مصطلحات موضوعية: bortezomib, immune checkpoint, MGMT, recurrent GBM, temozolomide, Th1/Th2 cytokine ratios, Immunologic diseases. Allergy, RC581-607

الوصف: Abstract Background Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes. Methods Ten patients received intravenous BTZ 1.3 mg/m2 on days 1, 4, and 7 during each 4th weekly TMZ‐chemotherapy starting on day 3 and escalated from 150 mg/m2 per oral 5 days/wk via 175 to 200 mg/m2 in cycles 1, 2, and 3, respectively. Adverse events and quality of life were evaluated by CTCAE and EQ‐5D‐5L questionnaire, and immunological biomarkers evaluated by flow cytometry and Luminex enzyme‐linked immunosorbent assay. Results Sequential BTZ + TMZ therapy was safe and well tolerated. Pain and performance of daily activities had greatest impact on patients' self‐reported quality of life and were inversely correlated with Karnofsky performance status. Patients segregated a priori into three groups, where group 1 displayed stable clinical symptoms and/or slower magnetic resonance imaging radiological progression, expanded CD4+ effector T‐cells that attenuated cytotoxic T‐lymphocyte associated protein‐4 and PD‐1 expression and secreted interferon γ and tumor necrosis factor α in situ and ex vivo upon stimulation with PMA/ionomycin. In contrast, rapidly progressing group 2 patients exhibited tolerised T‐cell phenotypes characterized by fourfold to sixfold higher interleukin 4 (IL‐4) and IL‐10 Th‐2 cytokines after BTZ + TMZ treatment, where group 3 patients exhibited intermediate clinical/radiological responses. Conclusion Sequential BTZ + TMZ treatment is safe and promotes Th1‐driven immunological responses in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2050-4527Test

الوصول الحر: https://doaj.org/article/6667890c0064459f9f27a9dbdca009cbTest

المؤلفون: Amber Leaver, Chris Abbott, Leif Oltedal

المصدر: Brain Stimulation, Vol 14, Iss 6, Pp 1738- (2021)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X21007452Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/1b590b18d5b14819a732e22941e49cb6Test

المؤلفون: Peter C.R. Mulders, Alberto Llera, Christian F. Beckmann, Mathieu Vandenbulcke, Max Stek, Pascal Sienaert, Ronny Redlich, Georgios Petrides, Mardien Leoniek Oudega, Leif Oltedal, Ketil J. Oedegaard, Katherine L. Narr, Peter O. Magnusson, Ute Kessler, Anders Jorgensen, Randall Espinoza, Verena Enneking, Louise Emsell, Annemieke Dols, Udo Dannlowski, Tom G. Bolwig, Hauke Bartsch, Miklos Argyelan, Amit Anand, Christopher C. Abbott, Philip F.P. van Eijndhoven, Indira Tendolkar

المصدر: Brain Stimulation, Vol 13, Iss 3, Pp 696-704 (2020)

مصطلحات موضوعية: Electroconvulsive therapy, Depression, Major depressive disorder, MRI, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Background: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. Objective: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). Methods: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. Results: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X20300425Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/3952106f9b7748f2956b82ef2ed749e1Test

المؤلفون: Jan Scott, Diego Hidalgo-Mazzei, Rebecca Strawbridge, Allan Young, Matthieu Resche-Rigon, Bruno Etain, Ole A. Andreassen, Michael Bauer, Djamila Bennabi, Andrew M. Blamire, Fawzi Boumezbeur, Paolo Brambilla, Nadia Cattane, Annamaria Cattaneo, Marie Chupin, Klara Coello, Yann Cointepas, Francesc Colom, David A. Cousins, Caroline Dubertret, Edouard Duchesnay, Adele Ferro, Aitana Garcia-Estela, Jose Goikolea, Antoine Grigis, Emmanuel Haffen, Margrethe C. Høegh, Petter Jakobsen, Janos L. Kalman, Lars V. Kessing, Farah Klohn-Saghatolislam, Trine V. Lagerberg, Mikael Landén, Ute Lewitzka, Ashley Lutticke, Nicolas Mazer, Monica Mazzelli, Cristina Mora, Thorsten Muller, Estanislao Mur-Mila, Ketil Joachim Oedegaard, Leif Oltedal, Erik Pålsson, Dimitri Papadopoulos Orfanos, Sergi Papiol, Victor Perez-Sola, Andreas Reif, Philipp Ritter, Roberto Rossi, Thomas Schulze, Fanny Senner, Fiona E. Smith, Letizia Squarcina, Nils Eiel Steen, Pete E. Thelwall, Cristina Varo, Eduard Vieta, Maj Vinberg, Michele Wessa, Lars T. Westlye, Frank Bellivier

المصدر: International Journal of Bipolar Disorders, Vol 7, Iss 1, Pp 1-10 (2019)

مصطلحات موضوعية: Bipolar, Precision, Personalization, Lithium, Response, Phenotype, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495

الوصف: Abstract Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.comTest/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s40345-019-0156-xTest; https://doaj.org/toc/2194-7511Test

الوصول الحر: https://doaj.org/article/57ee4627676f46439dd606349ebeed81Test