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   Table of Contents - Current issue
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October-December 2019
Volume 4 | Issue 4
Page Nos. 77-102

Online since Thursday, December 12, 2019

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RESEARCH ARTICLES  

Correlation between the microRNA-874-Sirtuin2-p53/nuclear factor-kappa B signaling pathway and depressive symptoms: a prospective multicenter study p. 77
Shan-Shan He, Hui-Duo Jiao, Qun-Qiang Wu, Chun-Hua Liao, Rui Liu
DOI:10.4103/2542-3932.271801  
Background and objective: Impaired hippocampal neurogenesis and local inflammatory responses are considered to be important mechanisms underlying depression. Sirtuin2 can inhibit cellular oxidative stress by regulating p53/nuclear factor-κB expression, prevent high-glucose-induced vascular endothelial cell damage, and interfere with neuroinflammation and blood-brain barrier destruction. Endogenous small RNAs or microRNAs (miRs) can be involved in the development and plasticity of the nervous system, which has been associated with depression. Our preliminary studies discovered that the 3′-untranslated region of Sirtuin2 messenger RNA (mRNA) is rich in miR-874 binding sites, suggesting that miR-874 may act as an upstream regulatory molecule for Sirtuin2. Therefore, we aim to explore the association between miR-874 and depressive symptoms through clinical trials. Participants and methods: This study will be conducted as a multicenter, prospective, clinical trial, at the Department of Rehabilitation at Tangdu Hospital of the Air Force Military Medical University and at the Department of Psychosomatic Medicine at Xijing Hospital of the Air Force Military Medical University, located in Xi’an, Shaanxi Province, China. A total of 50 patients with depression and 50 healthy controls will be recruited from these two locations. All patients with depression will be newly diagnosed, characterized by experiencing their first attack, and with no history of antidepressant administration. Moreover, no drug interventions will be utilized in this trial, for either the depressed or healthy cohorts. The trial protocol was approved by the Medical Ethics Committee of Tangdu Hospital of the Fourth Military Military Medical University in Xi’an, Shaanxi Province, China on June 1, 2018 (approval No. K201806-03). Protocol version is 1.0. All participants or their legal representatives will sign informed consent forms prior to the initiation of the trial. Patient recruitment began on October 31, 2018, and is expected to end on February 28, 2021. All data analysis was completed on August 1, 2021, and the trial will be completed on September 1, 2021. Outcome measures: Primary outcome measures include the expression levels miR-874 and Sirtuin2 mRNA in the blood. The secondary outcome measures include the levels of inflammatory factors, including interleukin-1β, interleukin-6, and tumor necrosis factor α, in the blood, the Hamilton Depression Rating Scale score, the Hamilton Anxiety Rating Scale score, the Global Assessment Function score, and the incidence of overall adverse events. We will also analyze the association between miR-874 expression levels and depression. Discussion: Determining whether any association exists between the miR-874-Sirtuin2-p53/nuclear factor-κB signaling pathway and depressive symptoms will assist in the exploration of the pathogenesis of depression and may provide novel therapeutic targets for the treatment of depression. Trial registration: This study was registered with the Chinese Clinical Trial Registry on October 17, 2018 (registration number: ChiCTR1800018933).
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Effects of aerobic exercise on adolescents with subthreshold mood symptoms: a randomized psycho-education controlled trial p. 84
Gui-Yun Xu, Kangguang Lin
DOI:10.4103/2542-3932.271803  
Background and objective: Adolescents often suffer from mood disorders and behavioral problems. Studies have shown that aerobic exercise can improve cognitive function, relieve depression, alleviate anxiety, and improve sleep. However, there have been few randomized controlled trials (RCT) evaluating the effects of aerobic exercise on cognition and mood symptoms in adolescents with subthreshold mood symptoms. Participants and methods: This RCT will include 224 adolescents with subthreshold mood symptoms from a middle school in Guangzhou, Guangdong Province, China. Participants will be randomly allocated to exercise intervention or psycho-education controlled group (n = 112/group). Participants in the exercise intervention group will undergo aerobic exercise at an intensity of 50–70% of the maximum heart rate for 30 minutes per day, 4 days per week for 3 successive months. Participants in the psycho-education controlled group will perform activities including three sections of general psychological education (one section of group game, one section of poetry reading, and one section of singing entertainment). Protocol version: 1.0. The study protocol was approved by the Institutional Review Board of Guizhou Brain Hospital (Guangzhou Huiai Hospital) on October 26, 2016 (approval No. 2016-048). Outcome measures: The primary outcome measure of this study is changes in depressive symptoms and neurocognitive function relative to baseline at the end of 12 weeks of intervention. Secondary outcome measures are anxiety symptoms, hypomanic symptoms, and change in brain connectivity relative to baseline at the end of 12 weeks of intervention. Discussion: The effects of aerobic exercise in adolescents with subthreshold mood symptoms will be evaluated. Registeration: This study was registered with ClinicalTrials.gov (identifier: NCT03300778) on October 3, 2017.
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Long-term follow-up of patients with multiple sclerosis treated with a cost-effective protocol from a rural medical center in India: a retrospective case series p. 90
Sadanandavalli Retnaswami Chandra, Nitin Ramanujam Chakravarthula, Thomas Gregor Issac, Mariamma Philip
DOI:10.4103/2542-3932.271802  
Background and objectives: Multiple sclerosis affects young adults resulting in dependency after 15 years of disease. Treatments are time-consuming, expensive and do not provide full protection. The purpose of this study is to assess the therapeutic effects of rational therapy on multiple sclerosis in patients from a tertiary centre, India. Subjects and methods: This retrospective case series study included 23 patients treated with a very cost-effective protocol that was practiced for three decades in a government medical college setting in a population of 250 patients. All rational options were explained to the patients who were diagnosed with multiple sclerosis according to modified Mc Donald criteria. The patients who were willing to undergo the scheduled regime were followed up. Multiple sclerosis relapse, lesion load, and Expanded Disability Status scale (EDSS) scores were evaluated at 1 and 3 years and thereafter in a need based way. This study was approved by the Institutional Review Board, National Institute of Mental Health And Neurosciences (NIMHANS), India. Results: The mean duration of illness of 23 patients with multiple sclerosis was 6.8 ± 5.23 years and the mean remission period was 4.09 ± 3.5 years. The mean EDSS score was 3.83 ± 0.78 at onset and it was 1.15 ± 0.5 after treatment. Thirteen (22%) patients had replaces during the above period of illness but were managed well with a pulse of 5 g methyl prednisolone. Conclusion: The treatment protocol for multiple sclerosis designed for patients from an Indian rural medical center is cost-effective and has very good effects on the control of relapse and progression.
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Transcranial magnetic stimulation combined with duloxetine improves attentional negativity bias in patients with depression: pilot study for a future trial p. 94
Dan-Na Zhou, Chang-Ming Wang, Xu Chen, Lei Feng
DOI:10.4103/2542-3932.251475  
Background and objective: Patients with depression often have cognitive deficits in perception, attention, executive control, and decision-making. Attentional negativity bias is a prominent symptom of depression. Indeed, during processing of negative emotional stimuli, the bilateral amygdala is over-activated, while prefrontal cortical activity decreases from baseline in patients with depression. Previous studies have reported that transcranial magnetic stimulation (TMS) can increase synaptic excitability. In this study, we investigate the effects of TMS combined with duloxetine versus duloxetine alone on attentional negativity bias in patients with depression. Subjects and Methods: A multi-center, randomized, double-blind, sham-stimulation, parallel-control trial will be conducted in Beijing Anding Hospital of Capital Medical University, Beijing, China. In the trial, 406 patients with depression will be included and will be randomly divided into a study group and a control group (n = 203 patients per group). Patients in both groups will receive oral administration of 60 mg/d duloxetine for 6 successive weeks, while patients in the study and control groups will undergo simultaneous TMS or sham-stimulation, respectively. The latter interventions will be performed once daily, five times a week with a 2 day interval between the first five and the last five procedures (10 times in total). This study was approved by Hospital Ethics Committee, Beijing Anding Hospital of Capital Medical University, China (approval No. 2017-79-2017111-2) on December 20, 2017. Protocol version: 3.0. Outcome measures: The primary outcome measure is effectiveness rate of the Hamilton Rating Scale for Depression–17-Item (HAMD17) after 6 weeks of treatment. The secondary outcome measures are: complete remission rate after 6 weeks of treatment; effectiveness rate after 1, 2, and 4 weeks of treatment; changes in HAMD17, Athens Insomnia Scale, Digit Symbol Substitution Test, 16-Item Quick Inventory of Depressive Symptomatology Self-Report Scale, 7-Item Generalized Anxiety Disorder Scale, Sheehan Disability Scale, Perceived Deficits Questionnaire-Depression, Arizona Sexual Experience Scale, and Mini-International Neuropsychiatric Interview suicide scores after 1, 2, 4, and 6 weeks of treatment relative to baseline; electroencephalogram results after 2 and 6 weeks of treatment; and safety indicators and adverse events after 6 weeks of treatment. Discussion: We plan to perform a study to provide preliminary evidence for the use of TMS combined with duloxetine to improve the attentional negativity bias in patients with depression. Trial registration: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-INR-17014075) on December 21, 2017.
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