Neuropeptide Y in Frontal Cortex Is Not Altered in Major Depression

Abstract: Previously, we reported a modest but significant reduction in the concentration of neuropeptide Y in frontal cortices from victims of suicide relative to age-matched natural or accidental death control subjects. The reduction in neuropeptide Y appeared to be greatest in a subgroup of victims of suicide for which there was indirect evidence of histories of depression. We pursued these initial findings in the present study by measuring neuropeptide Y concentrations in frontal cortices from natural or accidental death control subjects and from suicide victims in whom a firm diagnosis of major depression was established by psychiatric autopsy. Because several subjects with major depression had a comorbid diagnosis of alcoholism, a group of victims of suicide that had an Axis I diagnosis of alcohol dependence was also studied. No significant differences in neuropeptide Y concentrations were observed between control subjects and victims of suicide with major depression or victims of suicide with alcohol dependence. These findings do not support a role for neuropeptide Y in major depression.     

Effect of post-diagnosis exercise on depression symptoms,physical functioning and mortality in breast cancer survivors: A systematic review and meta-analysis of randomized control trials

BackgroundCancer is the second leading cause of death worldwide. Breast cancer, the most common cancer found in women, affects 2.1 million women annually and has the highest number of cancer related deaths. The objective of the current meta-analysis is to evaluate the effects of post-diagnosis exercises on depression, physical functioning, and mortality in breast cancer survivors.MethodsThe search for eligible articles was conducted through CINAHL, Medline/PubMed, Scopus, Cochrane, Emerald Insight and Web of Science, Embase database, MEDLINE In-Process, Elsevier, Google Scholar, PsycInfo, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Complementary Medicine (AMED), Biosis Previews, SPORTDiscus, PEDro scientific databases from 1974 to 2020. Following the exclusion procedure, 26 articles yielded for final analysis. The combined statistics for depression, physical functioning, and mortality in breast cancer survivors were calculated using standardized mean differences (SMD). Standard errors and 95% confidence intervals (CI) were converted to standard deviations as required. For mortality, combined statistics were calculated using hazard ratios (HR). The 95% CIs were converted to standard errors as required. The forest plots display point estimates and 95% CIs.ResultsStatistically significant improvements on levels of depression were identified following the exercise intervention, suggesting that post-diagnosis physical activity leads to a decrease in depression scores. Overall, post-diagnosis exercise led to a 37% reduction in the rate of breast cancer-specific mortality. The all-cause mortality rate was decreased by 39% with the inclusion of moderate physical activity as the part of daily routine.ConclusionsFuture studies should look at how to improve the quality of life while incorporating physical activity as a daily routine after breast-cancer treatment.     

非小细胞肺癌患者术后抑郁状况的影响因素及与生存质量和睡眠质量的相关性研究

摘要 目的：探讨非小细胞肺癌（NSCLC）患者术后抑郁状况的影响因素,分析术后抑郁与生存质量和睡眠质量的关系。方法：选取2019年1月～2021年1月在韶关市第一人民医院胸外科行手术治疗的 80例NSCLC患者,采用抑郁自评量表（SDS）评估其术后抑郁情况,根据评估结果将患者分为抑郁组（SDS评分≥50分,33例）和非抑郁组（SDS评分＜50分,47例）,单因素及多因素Logistic回归分析NSCLC患者术后抑郁的影响因素。采用肺癌患者生存质量测定量表（FACT-L）中文版（V4.0）、匹兹堡睡眠质量指数量表（PSQI）测评所有患者的生存质量和睡眠质量,Pearson相关性分析SDS评分与FACT-L、PSQI评分之间的关系。结果：抑郁组与非抑郁组间年龄、性别、文化程度、家庭收入水平、医疗费用支付方式、生活能否自理、肺癌TNM分期、术后是否并发肺炎有明显差异（P＜0.05）。进一步多因素分析显示,术后并发肺炎、肺癌TNM分期Ⅲ期、女性、大专以下文化程度是NSCLC患者术后抑郁的危险因素（P＜0.05）。抑郁组FACT-L评分低于非抑郁组,PSQI评分高于非抑郁组（P＜0.05）。SDS评分与FACT-L评分呈负相关,与PSQI评分呈正相关（P＜0.05）。结论：术后并发肺炎、肺癌TNM分期Ⅲ期、女性、文化程度低是影响NSCLC患者术后抑郁的因素,术后抑郁的发生会降低患者的生存质量和睡眠质量。     

阿戈美拉汀联合舍曲林治疗抑郁症伴失眠的疗效及对睡眠质量评分、多导睡眠监测参数和血清神经递质的影响

摘要 目的：观察阿戈美拉汀联合舍曲林治疗抑郁症伴失眠的疗效及对睡眠质量评分、多导睡眠（PSG）监测参数和血清神经递质的影响。方法：选取2020年4月~2021年12月期间来贵州省第二人民医院就诊的80例抑郁症伴失眠患者作为观察对象,采用随机数字表法分为实验组和对照组各40例,对照组患者接受舍曲林治疗,实验组患者接受阿戈美拉汀联合舍曲林治疗,对比两组疗效、匹兹堡睡眠质量指数（PQSI）评分、PSG相关指标参数、汉密尔顿抑郁量表（HAMD）评分、血清神经递质水平变化,记录两组治疗期间不良反应发生情况。结果：实验组的临床总有效率为90.00%（36/40）,高于对照组的67.50%（27/40）,差异有统计学意义（P<0.05）。两组治疗8周后PSQI、HAMD评分均下降,且实验组的变化程度大于对照组（P<0.05）。两组治疗8周后睡眠总时间（TST）、睡眠效率（SE）、非快速眼动睡眠阶段3+4的百分比（SWS）、快速眼动睡眠阶段睡眠时间（RT）增加,非快速眼动睡眠阶段1的百分比（S1）、非快速眼动睡眠阶段2的百分比（S2）减少,且实验组的变化程度大于对照组（P<0.05）。两组治疗8周后去甲肾上腺素（NE）、5-羟色胺（5-HT）水平均升高,且实验组的升高程度大于对照组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：阿戈美拉汀联合舍曲林治疗抑郁症伴失眠,可有效改善抑郁和失眠症状,同时还可调节血清神经递质水平,是一个较为安全可靠的治疗方案。     

老年肿瘤病人抑郁症状影响因素的调查与心理干预

目的:调查分析老年肿瘤病人抑郁的影响因素,寻求解决办法。方法:对本院部分住院老年肿瘤病人发放老年抑郁量表进行调查与分析。结果:老年肿瘤病人发生抑郁的几率远大于一般人群。结论:在肿瘤的治疗过程中,只关注躯体疾病是不够的,应建立良好的社会支持系统,除了医护人员外,还要充分发挥和利用家庭、朋友、社会团体等其他社会支持的作用。     

慢性应激抑郁大鼠学习记忆及海马非对称性超微结构的改变

目的：探讨慢性不可预见性应激抑郁模型大鼠大脑海马非对称性超微结构与学习记忆能力的改变。方法：SD雄性大鼠20只,随机分为正常对照组与抑郁模型组,每组10只。采用慢性轻度不可预见性应激21d及单笼饲养方法建立抑郁模型,应激前以及应激21d末对两组大鼠进行旷场实验、液体消耗实验及体重测量,对大鼠进行避暗穿梭实验,测试其学习记忆能力,之后活杀动物,取出大鼠左右海马,制作常规电镜标本,观察海马超微结构的改变。结果：在穿梭变实验中抑郁大鼠学习记忆潜伏期减少,进入暗箱错误积分增多。抑郁大鼠左右侧海马超微结构中左侧海马较正常对照组神经细胞及胶质细胞变化明显,表现为内质网扩张,溶酶体增多。而右侧海马远不及左侧损伤严重。结论：慢性不可预见性应激抑郁大鼠学习记忆能力显著下降,其可能与海马组织在应激过程受到的累积损伤有关,且抑郁大鼠海马损伤呈非对称表现。     

Design, synthesis, and structure-activity relationships of a series of 2-Ar-8-methyl-5-alkylaminoquinolines as novel CRF(1) receptor antagonists

We designed and synthesized a series of 2-Ar-8-methyl-5-alkylaminolquinolines as potent corticotropin-releasing factor 1 (CRF(1)) receptor antagonists. The structure-activity relationships of substituents at each position (R(3), R(5), R(5'), and R(8)) was investigated. By derivatization, three compounds (6, 14b, and 14c) were identified as orally active CRF(1) receptor antagonists.     

GluN2B-containing NMDA receptors as possible targets for the neuroprotective and antidepressant effects of fluoxetine

Accumulating evidence has indicated the involvement of glutamatergic neurotransmission in the pathophysiology of excitotoxicity and in the mechanism of action of antidepressants. We have previously shown that tricyclic desipramine and the selective serotonin reuptake inhibitor fluoxetine inhibit NMDA receptors (NMDARs) in the clinically relevant, low micromolar concentration range. As the different subtypes of NMDARs are markedly different in their physiological and pathological functions, our aim was to investigate whether the effect of antidepressants is subtype-specific. Using whole-cell patch-clamp recordings in rat cortical cell cultures, we studied the age-dependence of inhibition of NMDA-induced currents after treatment with desipramine and fluoxetine, as the expression profile of the NMDAR subtypes changes as a function of days in vitro. We also investigated the inhibitory effect of these antidepressants on NMDA-induced currents in HEK 293 cell lines that stably expressed rat recombinant NMDARs with GluN1a/GluN2A or GluN1a/GluN2B subunit compositions. The inhibitory effect of desipramine was not age-dependent, whereas fluoxetine displayed a continuously decreasing inhibitory profile, which was similar to the GluN1/GluN2B subtype-selective antagonist ifenprodil. In HEK 293 cells, desipramine equally inhibited NMDA currents in both cell lines, whereas fluoxetine showed an inhibitory effect only in cells that expressed the GluN1/GluN2B subtype. Our data show that fluoxetine is a selective inhibitor of GluN2B-containing NMDARs, whereas desipramine inhibits both GluN1/GluN2A and GluN1/GluN2B subtypes. As the clinical efficacy of these drugs is very similar, the putative NMDAR-associated therapeutic effect of antidepressants may be mediated only via inhibition of the GluN2B-containing subtype. The manifestation of the GluN1/GluN2B-selectivity of fluoxetine suggests the neuroprotective potential for this drug in both acute and chronic neurodegenerative disorders.     

Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats

A growing body of evidence has pointed to a relationship between oxidative stress and depression. Thus, the present study was aimed at evaluating the effects of the antioxidants n-acetylcysteine (NAC), deferoxamine (DFX) or their combination on sweet food consumption and oxidative stress parameters in rats submitted to 40 days of exposure to chronic mild stress (CMS). Our results showed that in stressed rats treated with saline, there was a decrease in sweet food intake and treatment with NAC or NAC in combination with DFX reversed this effect. Treatment with NAC and DFX decreased the oxidative damage, which include superoxide and TBARS production in submitochondrial particles, and also thiobarbituric acid reactive substances (TBARS) levels and carbonyl proteins in the prefrontal cortex, amygdala and hippocampus. Treatment with NAC and DFX also increased the activity of the antioxidant enzymes, superoxide dismutase and catalase in the same brain areas. Even so, a combined treatment with NAC and DFX produced a stronger increase of antioxidant activities in the prefrontal cortex, amygdala and hippocampus. The results described here indicate that co-administration may induce a more pronounced antidepressant activity than each treatment alone. In conclusion, these results suggests that treatment with NAC or DFX alone or in combination on oxidative stress parameters could have positive effects against neuronal damage caused by oxidative stress in major depressive disorders.