Cyclooxygenase-2 inhibition prevents stress induced amygdala activation and anxiety-like behavior

Stress is a major risk factor for the development and exacerbation of mood and anxiety disorders, and recent studies have suggested inflammatory contributions to the pathogenesis of depression. Interestingly, pharmacological inhibition of cyclooxygenase-2 (COX-2) has shown promise in the treatment of affective disorders in small scale clinical studies; however, the mechanisms by which COX-2 inhibition affects behavioral domains relevant to affective disorders are not well understood. Here, we examined the effects of pharmacological inhibition of COX-2 with the highly selective inhibitor Lumiracoxib (LMX) on anxiety-like behavior and in vivo basolateral amygdala (BLA) neural activity in response to acute restraint stress exposure. In male mice, pretreatment with LMX prevented the increase in BLA calcium transients induced by restraint stress and prevented anxiogenic behavior seen after restraint stress exposure. Specifically, acute injection of LMX 5 mg kg⁻¹ reduced anxiety-like behavior in the light–dark box (LD) and elevated-zero maze (EZM). In addition, in vivo fiber photometry studies showed that acute stress increased calcium transients and the predicted action potential frequency of BLA neurons, which was also normalized by acute LMX pretreatment. These findings indicate pharmacological inhibition of COX-2 can prevent acute stress-induced increase in BLA cellular activity and anxiety-like behavior and provides insights into the neural mechanisms by which COX-2 inhibition could affect anxiety domain symptoms in patients with affective disorders.     

Depression treatment use among stroke individuals with depression: A cross-sectional analysis of the Medical Expenditure Panel Survey

BackgroundDepression is the most prevalent psychiatric comorbidity among stroke individuals. Despite the effectiveness of antidepressants and psychotherapy, data on the use of these treatments among stroke survivors is limited.ObjectiveThe main objective of this study was to document prevalence of antidepressant use, types of antidepressants utilized, and adherence to antidepressants among stroke individuals.MethodsRetrospective, cross-sectional data obtained from the Medical Expenditure Panel Surveys (MEPS), for the years 2011, 2013 and 2015, was utilized for this study. Treatment for depression was categorized into three mutually exclusive categories: 1) antidepressants only, 2) antidepressants and psychotherapy (combination), and 3) No treatment. Adherence to antidepressants was measured using the Proportion of Days Covered (PDC) ratio. Adherence between antidepressant only and combination therapy group was compared using Student's t-test. A multinomial logistic regression analysis was used to further examine the association between patient characteristics and likelihood of receiving depression treatment.ResultsA total of 759 stroke individuals with comorbid depression were identified. Of these, 51.2% utilized only antidepressants, 12.6% utilized a combination treatment of antidepressants and psychotherapy and 31.7% did not receive treatment for depression. Selective Serotonin Reuptake Inhibitors (SSRI's) was the most commonly used antidepressants in the stroke population. Males (P = 0.04), age group of 40–64 years (P < 0.001), and African Americans (P = 0.02) constituted for the highest proportions of untreated stroke survivors. Among treated stroke individuals, adherence was higher for combination therapy users compared to those using antidepressants only (mean PDC = 65.8 ± 6.89 and 57.6 ± 3.74, respectively).ConclusionAlmost 70% of stroke individuals received some form of treatment for depression and several patient-related factors (gender, age, race, marital status, and comorbidity burden) were associated with the utilization of depression treatment. Future researchers need to investigate the factors responsible for lack of depression treatment in stroke individuals and policy makers should aim for a more patient centered care.     

研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效关系

目的：研析奥氮平治疗老年晚期癌症患者抑郁状态的血药浓度与临床疗效的关系，促进合理用药。方法：80例这类患者服用2.5 ~ 10 mg·d-1奥氮平，应用全自动二维液相色谱法（2D-LC/UV）检测患者用药后4周内每周奥氮平血药浓度（C奥氮平）；采用汉密尔顿抑郁量表（HAMD-24）于治疗前、治疗后4周内每周评估疗效，应用线性回归方程分析奥氮平剂量与血药浓度相关性，运用Logistic回归和受试者工作曲线（ROC）分析奥氮平血药浓度与临床疗效相关性；采用副反应量表（TESS）评估药物不良反应。结果：奥氮平日剂量（D日）和C奥氮平线性方程呈正相关（r=0.634，P<0.001）。治疗的第1、2、3、4周末，有效组与无效组患者D日、C奥氮平、HAMD-24量表减分率存在显著性差异（P<0.05）。经Logistic回归分析得出年龄大、奥氮平血药浓度低是导致奥氮平治疗效果不理想的影响因素。以C奥氮平作为疗效预测因子绘制治疗第1、2、3、4周末ROC曲线，得出约登指数最大时对应的最佳临界值切点分别11.18、13.89、11.55、12.44 ng·mL-1；未发现C奥氮平与TESS量表评分相关（P>0.05）。结论：奥氮平血药浓度与日剂量、临床疗效密切相关，治疗老年晚期癌症患者抑郁状态最低有效血药浓度范围为11~14 ng·mL-1。     

The impact of ethnicity on the clinical presentations of spinocerebellar ataxia type 3

BackgroundFor a variety of sporadic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, it is well-established that ethnicity does affect the disease phenotypes. However, how ethnicity contributes to the clinical symptoms and disease progressions in monogenetic disorders, such as spinocerebellar ataxia type 3 (SCA3), remains less studied.MethodsWe used multivariable linear and logistical regression models in 257 molecularly-confirmed SCA3 patients (66 Caucasians, 43 African Americans, and 148 Asians [composed of 131 Chinese and 17 Asian Americans]) to explore the influence of ethnicity on age at onset (AAO), ataxia severity, and non-ataxia symptoms (i.e. depression, tremor, and dystonia).ResultsWe found that Asians had significantly later AAO, compared to Caucasians (β = 4.75, p = 0.000) and to African Americans (β = 6.64, p = 0.000) after adjusting for the pathological CAG repeat numbers in ATXN3. African Americans exhibited the most severe ataxia as compared to Caucasians (β = 3.81, p = 0.004) and Asians (β = 4.39, p = 0.001) after taking into consideration of the pathological CAG repeat numbers in ATXN3 and disease duration. Caucasians had a higher prevalence of depression than African Americans (β = 1.23, p = 0.040). Ethnicity had no influence on tremor or dystonia.ConclusionsEthnicity plays an important role in clinical presentations of SCA3 patients, which could merit further clinical studies and public health consideration. These results highlight the role of ethnicity in monogenetic, neurodegenerative disorders.     

湖北农村女性打麻将和看手机行为与抑郁状况的相关性

  目的   分析湖北农村女性打麻将和看手机行为与抑郁状况的关系, 为改善农村女性身心健康提供建议。   方法   采用分层整群抽样方法调查湖北7个县/市8个行政村1 367例成年妇女, 抑郁状况的测量采用流调中心抑郁自评量表(Center for Epidemiologic Studies Depression Scale-10, CESD-10), 并进行百分数转化。分值越高, 抑郁程度越低, 心理健康状况越好。   结果   15~44岁的妇女的CESD-10得分(77.63±13.95)高于45-64岁(73.17±17.01)和≥65岁(69.25±18.16)的得分(P < 0.001)。多元线性回归结果显示, 每天看手机时间与农村妇女抑郁状况之间的相关有统计学意义(均有P < 0.05), 尤其对45-64岁女性抑郁状况的影响具有显著统计学意义(均有P < 0.05), 看手机时间越长, 抑郁程度越高; 打麻将对各年龄段妇女抑郁状况影响均没有统计学意义(均有P > 0.05)。   结论   看手机行为与湖北农村女性抑郁状况之间存在相关性, 减少农村女性特别是中年妇女的手机使用是今后健康教育与妇联工作中值得重视的。     

New immunosuppressive agents in transplantation

Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.     

Depression among caregivers of patients with dementia: Associative factors and management approaches

As elderly people increasingly come to represent a higher proportion of the world’s population, various forms of dementia are becoming a significant chronic disease burden. The World Health Organization emphasizes dementia care as a public health priority and calls for more support for family caregivers who commonly play a significant, central role in dementia care. Taking care of someone with dementia is a long-term responsibility that can be stressful and may lead to depression among family caregivers. Depression and related behavioral and cognitive changes among caregivers could in turn affect the status and prognosis of the dementia patient. This review article explores depression in dementia caregivers and summarizes proposed mechanisms, associated factors, management and research findings, and proposes future research directions.