scholarly journals Immunoregulation and antidepressant effect of ketamine

2021 ◽  
Vol 12 (1) ◽  
pp. 218-236
Author(s):  
Nan Zhang ◽  
Lihua Yao ◽  
Peilin Wang ◽  
Zhongchun Liu
Keyword(s):  
Disease Burden ◽  
Severe Disease ◽  
Mental Health Disorder ◽  
Antagonistic Effect ◽  
Antidepressant Effect ◽  
Future Research ◽  
Recurrence Rates ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Common Mental Health Disorder

Abstract Major depressive disorder (MDD) is a common mental health disorder that brings severe disease burden worldwide. Traditional antidepressants are mainly targeted at monoamine neurotransmitters, with low remission rates and high recurrence rates. Ketamine is a noncompetitive glutamate N-methyl-d-aspartate receptor (NMDAR) antagonist, and its rapid and powerful antidepressant effects have come to light. Its antidepressant mechanism is still unclarified. Research found that ketamine had not only antagonistic effect on NMDAR but also strong immunomodulatory effect, both of which were closely related to the pathophysiology of MDD. Although there are many related studies, they are relatively heterogeneous. Therefore, this review mainly describes the immune mechanisms involved in MDD and how ketamine plays an antidepressant role by regulating peripheral and central immune system, including peripheral inflammatory cytokines, central microglia, and astrocytes. This review summarizes the related research, finds out the deficiencies of current research, and provides ideas for future research and the development of novel antidepressants.

Effect of NMDAR antagonists in the tetrabenazine test for antidepressants: comparison with the tail suspension test

2015 ◽  
Vol 27 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Phil Skolnick ◽  
Tomasz Kos ◽  
Janusz Czekaj ◽  
Piotr Popik
Keyword(s):  
First Generation ◽  
Partial Agonist ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Class Effect ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Resistant Depression ◽  
Suspension Test

ObjectiveThe N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine, produces rapid and enduring antidepressant effect in patients with treatment-resistant depression. Similar dramatic effects have not been observed in clinical trials with other NMDAR antagonists indicating ketamine may possess unique pharmacological properties. Tetrabenazine induces ptosis (a drooping of the eyelids), and the reversal of this effect, attributed to a sympathomimetic action, has been used to detect first-generation antidepressants, as well as ketamine. Because the actions of other NMDAR antagonists have not been reported in this measure, we examined whether reversal of tetrabenazine-induced ptosis was unique to ketamine, or a class effect of NMDAR antagonists.MethodsThe effects of ketamine and other NMDAR antagonists to reverse tetrabenazine-induced ptosis were examined and compared with their antidepressant-like effects in the tail suspension test (TST) in mice.ResultsAll the NMDAR antagonists tested produced a partial reversal of tetrabenazine-induced ptosis and, as expected, reduced immobility in the TST. Ketamine, memantine, MK-801 and AZD6765 were all about half as potent in reversing tetrabenazine-induced ptosis compared to reducing immobility in the TST, while an NR2B antagonist (Ro 25-6981) and a glycine partial agonist (ACPC) were equipotent in both tests.ConclusionThe ability to reverse tetrabenazine-induced ptosis is a class effect of NMDAR antagonists. These findings are consistent with the hypothesis that the inability of memantine, AZD6765 (lanicemine) and MK-0657 to reproduce the rapid and robust antidepressant effects of ketamine in the clinic result from insufficient dosing rather than a difference in mechanism of action among these NMDAR antagonists.

Ketamine Treatment in Depression: A Systematic Review of Clinical Characteristics Predicting Symptom Improvement

2020 ◽  
Vol 20 (15) ◽  
pp. 1398-1414 ◽  
Author(s):  
Darby J.E. Lowe ◽  
Daniel J. Müller ◽  
Tony P. George
Keyword(s):  
Clinical Features ◽  
Clinical Characteristics ◽  
Bipolar Depression ◽  
Antidepressant Effect ◽  
Future Research ◽  
Symptom Improvement ◽  
Randomized Controlled ◽  
Treatment Of Depression ◽  
Future Direction

Ketamine has been shown to be efficacious for the treatment of depression, specifically among individuals who do not respond to first-line treatments. There is still, however, a lack of clarity surrounding the clinical features and response periods across samples that respond to ketamine. This paper systematically reviews published randomized controlled trials that investigate ketamine as an antidepressant intervention in both unipolar and bipolar depression to determine the specific clinical features of the samples across different efficacy periods. Moreover, similarities and differences in clinical characteristics associated with acute versus longer-term drug response are discussed. Similarities across all samples suggest that the population that responds to ketamine’s antidepressant effect has experienced chronic, long-term depression, approaching ketamine treatment as a “last resort”. Moreover, differences between these groups suggest future research to investigate the potential of stronger efficacy towards depression in the context of bipolar disorder compared to major depression, and in participants who undergo antidepressant washout before ketamine administration. From these findings, suggestions for the future direction of ketamine research for depression are formed.

scholarly journals People with amyotrophic lateral sclerosis and their caregivers: what matters most?

2021 ◽  
pp. bmjspcare-2020-002741
Author(s):  
Paola Brunori ◽  
Maria Grazia Celani ◽  
Angelo Alberto Bignamini ◽  
Marzia Carlini ◽  
Rossella Papetti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Burden ◽  
Anger Management ◽  
Care Service ◽  
Group Discussion ◽  
Future Research ◽  
Text File ◽  
Medical Issues ◽  
Research Questions ◽  
Lateral Sclerosis

ObjectivesThe aim of this study is to collect the perspectives and values of people affected by amyotrophic lateral sclerosis (ALS) and their carers to offer clinicians, researchers and policymakers aspects which are precious in prioritising future research questions and reshaping care service organisations in a participatory approach.Design and settingCohort study using ALS Umbria, the electronic database in Italy.ParticipantsEleven patients and 33 carers who agreed to participate in the study were divided into six focus groups by ‘status’ (patient or carer) and by four severity levels of ‘burden of disease’.MethodsA semiquantitative analysis was undertaken. Each recorded group discussion was transcribed into text file and independently read by two psychologists and two ALS specialists to blindly identify needs, emotions and medical issues, which are the key semantic meanings expressed. Any disagreement in interpretation was resolved through consultation among authors.ResultsCarers pronounced significantly more words related to patient’s disease burden they cared. 40% of subjects expressed the need for ‘assistance’, regardless of the disease burden. ‘Anger’ alone represented more than 1/4 of all expressed emotions and was more common in patients than in carers (73% vs 36%, p=0.077). The most frequent medical issue expressed by 1/3 of participants was ‘difficulty in communication’.ConclusionThis study has given voice to the expectations of those affected by the burden of ALS. ‘Welfare assistance’, ‘anger management’ and resolution of ‘difficulties in communication’ represent issues that need to be analysed in a common prioritised research agenda with sensible and shared outcome measures to implement patient-centred medicine.

scholarly journals Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

2021 ◽  
Vol 5 ◽  
pp. 247054702110142
Author(s):  
Alexandra A. Alario ◽  
Mark J. Niciu
Keyword(s):  
Treatment Response ◽  
Antidepressant Treatment ◽  
A Priori ◽  
Antidepressant Effect ◽  
Aspartate Receptor ◽  
Neurophysiological Studies ◽  
All Cause Mortality ◽  
Antidepressant Efficacy ◽  
Glutamate Modulators ◽  
Response Biomarkers

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

scholarly journals Therapeutic Potential of Hericium erinaceus for Depressive Disorder

2019 ◽  
Vol 21 (1) ◽  
pp. 163 ◽  
Author(s):  
Pit Shan Chong ◽  
Man-Lung Fung ◽  
Kah Hui Wong ◽  
Lee Wei Lim
Keyword(s):  
Depressive Disorder ◽  
Disease Burden ◽  
Therapeutic Potential ◽  
Fruiting Bodies ◽  
Hericium Erinaceus ◽  
Treatment Of Depression ◽  
Antidepressant Effects ◽  
Potential Benefits ◽  
Potential Alternative ◽  
Global Disease Burden

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion’s mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson’s disease, and Alzheimer’s disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

scholarly journals Tics in patients with encephalitis

2021 ◽  
Author(s):  
James Badenoch ◽  
Tamara Searle ◽  
Iona Watson ◽  
Andrea E. Cavanna
Keyword(s):  
Movement Disorders ◽  
Future Research ◽  
Viral Pathogens ◽  
Encephalitis Lethargica ◽  
Scientific Databases ◽  
Aspartate Receptor ◽  
Immune Mediated ◽  
Jakob Disease ◽  
Meta Analyses ◽  
Practical Implications

Abstract Background Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies. Objective This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis. Methods We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-d-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed. Discussion The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.

scholarly journals Healthcare utilization and costs in adults with SLE in the United Kingdom: a real-world observational retrospective cohort analysis

2021 ◽  
Author(s):  
Mihail Samnaliev ◽  
Volkan Barut ◽  
Sharada Weir ◽  
Julia Langham ◽  
Sue Langham ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthcare Costs ◽  
Severe Disease ◽  
Cohort Analysis ◽  
Practice Research ◽  
Future Research ◽  
First Year ◽  
Clinical Practice Research Datalink ◽  
Comorbid Conditions ◽  
The Uk

Abstract Objectives To describe direct healthcare costs for adults with systemic lupus erythematosus (SLE) in the UK over time and by disease severity and encounter type. Methods Patients aged ≥18 years with SLE were identified using the linked Clinical Practice Research Datalink—Hospital Episode Statistics database from January 2005 to December 2017. Patients were classified as having mild, moderate, or severe disease using an adapted claims-based algorithm based on prescriptions and comorbid conditions. We estimated all-cause healthcare costs and incremental costs associated with each year of follow-up compared with a baseline year adjusting for age, sex, disease severity, and comorbid conditions (2017 UK pounds). Results We identified 802 patients; 369 (46.0%) with mild, 345 (43.0%) moderate, and 88 (11.0%) severe disease. The mean all-cause cost increased in the 3 years before diagnosis, peaked in the first year after diagnosis and remained high. Adjusted total mean annual increase in costs per patient was £4476 (95% confidence interval £3809–5143) greater in the year of diagnosis compared with the baseline year (p < 0.0001). The increase in costs per year were 4.7-fold and 1.6-fold higher among patients with severe SLE compared with those with mild and moderate SLE respectively. Primary care utilisation was the leading component of costs during the first year of diagnosis. Conclusion The healthcare costs for patients with SLE in the UK are substantial, remain high after diagnosis and increase with increasing severity. Future research should assess whether earlier diagnosis and treatment may reduce disease severity and associated high healthcare costs.

scholarly journals Autoregulation in Resistance Training for Lower Limb Tendinopathy: A Potential Method for Addressing Individual Factors, Intervention Issues and Inadequate Outcomes

2020 ◽  
Author(s):  
Ian Burton
Keyword(s):  
Resistance Training ◽  
Musculoskeletal Disorders ◽  
Lower Limb ◽  
Potential Method ◽  
Future Research ◽  
Individual Factors ◽  
Recurrence Rates ◽  
High Incidence ◽  
Training Protocols

Musculoskeletal disorders such as tendinopathy are having an increasing burden on society and health systems. Tendinopathy is responsible for up to 30% of musculoskeletal disorders, having a high incidence in athletes and the general population. Although resistance training has shown short-term effectiveness for treating lower limb tendinopathy, more comprehensive exercise protocols and progression methods are required due to poor long-term outcomes. The most common resistance training protocols are pre-determined and standardised, which presents significant limitations. Current standardized protocols do not adhere to scientific resistance training principles and do not consider individual factors or take the importance of individualised training into account. Resistance training programs in tendinopathy are currently not achieving required intensity and dosage, leading to high recurrence rates. Therefore, better methods for individualising and progressing resistance training are required to improve outcomes. One potential method is autoregulation, which allows individuals to progress training at their own rate, taking individual factors into account. Despite being found effective for increasing strength in healthy athletes, autoregulation methods have not been investigated in tendinopathy. The purpose of this article was threefold: first to give an overview of individual factors in tendinopathy and current resistance training protocols in tendinopathy and their limitations. Secondly, to give an overview of the history, methods and application of autoregulation strategies both in sports performance and physiotherapy. Finally, a theoretical adaptation of a tendinopathy resistance training protocol with autoregulation methods is presented, providing an example of how the method could be implemented in clinical practice or future research.

The association of oxytocin with major depressive disorder: role of confounding effects of antidepressants

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shiyi Xie ◽  
Yan Hu ◽  
Li Fang ◽  
Shijia Chen ◽  
Benson O.A. Botchway ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Receptor Gene ◽  
Predictive Ability ◽  
High Rate ◽  
Future Research ◽  
Targeted Prevention ◽  
Major Depressive ◽  
Antidepressant Effects ◽  
Psychiatric Syndrome

Abstract Major depressive disorder is a genetic susceptible disease, and a psychiatric syndrome with a high rate of incidence and recurrence. Because of its complexity concerning etiology and pathogenesis, the cure rate of first-line antidepressants is low. In recent years, accumulative evidences revealed that oxytocin act as a physiological or pathological participant in a variety of complex neuropsychological activities, including major depressive disorder. Six electronic databases (Web of Science, PubMed, Scopus, Google Scholar, CNKI, and Wanfang) were employed for researching relevant publications. At last, 226 articles were extracted. The current review addresses the correlation of the oxytocin system and major depressive disorder. Besides, we summarize the mechanisms by which the oxytocin system exerts potential antidepressant effects, including regulating neuronal activity, influencing neuroplasticity and regeneration, altering neurotransmitter release, down regulating hypothalamic–pituitary–adrenal axis, anti-inflammatory, antioxidation, and genetic effects. Increasing evidence shows that oxytocin and its receptor gene may play a potential role in major depressive disorder. Future research should focus on the predictive ability of the oxytocin system as a biomarker, as well as its role in targeted prevention and early intervention of major depressive disorder.

Rift Valley Fever and the Changing Environment

2020 ◽  
pp. 1496-1516
Author(s):  
Johanna Lindahl ◽  
Bernard Bett ◽  
Timothy Robinson ◽  
Delia Grace
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Environmental Changes ◽  
Rift Valley Fever Virus ◽  
Severe Disease ◽  
Land Use Changes ◽  
Future Research ◽  
Valley Fever ◽  
Vector Borne Diseases ◽  
Vector Borne

Rift Valley fever is a severe disease affecting both humans and animals. The Rift Valley fever virus can be transmitted by body fluids, and the most common way for humans to get infected is from animals. The virus is also vector-borne and can be transmitted by many species of mosquitoes. As with other vector-borne diseases, the epidemiology may vary in response to environmental changes. Here the effects of climate and land use changes on Rift Valley fever, as well as on other vector-borne diseases, are discussed. The effect of irrigation in East Africa on inter-epidemic transmission of RVF is discussed in greater detail, followed by recommendations for future research and actions.

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