Large-scale observational studies of hypericum extracts in patients with depressive disorders—a systematic review

We present a systematic review of observational studies of hypericum extracts in the treatment of depressive disorders. We included non-randomized studies with at least 100 patients suffering from depressive disorders treated with hypericum mono-preparations for at least 4 weeks, which reported clinical outcomes. Potentially relevant studies were identified through searches in electronic databases (Medline, PubMed), contacts with manufacturers, and handsearching of proceedings of phytomedicine congresses. Information on patients, interventions, methods an results were extracted by two reviewers. Sixteen studies including a total of 34,804 (range 101-11,296) patients met the inclusion criteria. Most studies investigated short-term effects (4-6 weeks) in patients with mild to moderate depression. Response rates (according to physician assessment) varied between 65% and 100%, the proportion of patients dropping out due to side effects varied between 0.0% and 2.8%. Two studies investigated long-term effects (52 weeks). Reponse rates were 60% and 69%, respectively, and the proportions of patients dropping out due to side effects were 3.4% and 5.7%, respectively. Serious side effects or interactions were not reported in any study. The quality of reporting was insufficient in the majority of publications. The available studies show that hypericum extract are well tolerated and seem to be effective in routine treatment of mild to moderate depressive disorders.     

Alarin-induced antidepressant-like effects and their relationship with hypothalamus–pituitary–adrenal axis activity and brain derived neurotrophic factor levels in mice

Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s).     

Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Synthesis,biological characterization,and development of a pharmacophore model

In this study we have generated a pharmacophore model of triple uptake inhibitor compounds based on novel asymmetric pyran derivatives and the newly developed asymmetric furan derivatives. The model revealed features important for inhibitors to exhibit a balanced activity against dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). In particular, a ‘folded’ conformation was found common to the active pyran compounds in the training set and was crucial to triple uptake inhibitory activity. Furthermore, the distances between the benzhydryl moiety and the N-benzyl group as well as the orientation of the secondary nitrogen were also important for TUI activity. We have validated our findings by synthesizing and testing novel asymmetric pyran analogs. The present work has also resulted in the discovery of a new series of asymmetric tetrahydrofuran derivatives as novel TUIs. Lead compounds 41 and 42 exhibited moderate TUI activity. Interestingly, the highest TUI activity by lead tetrahydrofuran compounds for example, 41 and 42, was exhibited in a stereochemical preference similar to pyran TUI for example, D-161.     

团体心理咨询对甲减患者焦虑抑郁情绪的影响

目的:探讨团体心理咨询对甲减患者焦虑、抑郁情绪的影响,为改善甲减患者心理健康状况提供参考依据。方法:选择2014年1月至2016年1月在我院确诊为甲减后焦虑、抑郁的60例患者,按照随机数字表法分为对照组(n=30)和研究组(n=30)。对照组给予常规药物治疗,研究组在对照组基础上给予6周的团体心理咨询治疗。治疗后6周、3个月测量两组患者的甲状腺功能情况,并对比治疗前、治疗后6周及治疗后3个月两组的汉密尔顿焦虑量表(HAMA)评分和汉密尔顿抑郁量表(HAMD)评分,另外治疗后3个月比较两组患者的满意度。结果:治疗后6周对照组甲状腺功能正常24例,异常6例,研究组正常25例,异常5例;治疗3个月两组甲状腺功能正常均为30例,两组患者治疗后6周、3个月的甲状腺功能情况比较无统计学差异(P0.05)。治疗后6周、3个月两组HAMA、HAMD评分较治疗前降低,且研究组较对照组的评分更低(P0.05)。治疗后3个月研究组患者满意度为96.67%(29/30),明显高于对照组的66.67%(20/30)(P0.05)。结论:团体心理咨询在甲减后焦虑、抑郁患者的治疗中的作用明显,可显著改善患者的心理健康状况,提高患者的满意度。     

国内7省市老年人抑郁症的检出率及影响因素分析

目的:调查分析国内7省市老年人抑郁症的检出率及特点,并从老年人基本情况、躯体健康、认知功能等方面综合分析抑郁症的影响因素。方法:采用GDS-30量表分析2011-2012年在北京、上海、哈尔滨、西安、成都、长沙和重庆市及周边乡镇的9200名60岁以上老年抑郁症的发生情况,并分析影响抑郁检出率的相关因素。结果:调查老年对象的抑郁症检出率为17.2%,其中男性为15%,女性为19.6%。女性老年人在各个年龄段的抑郁症检出率均高于男性。抑郁症检出率随着年龄的增加逐渐增加。文化水平、健康自评、认知功能与抑郁症检出率密切相关。结论:抑郁症是国内7省市老年人常见的心理疾病,女性、高龄、低文化水平、健康自评差、认知功能障碍的老年人患抑郁症的几率更高。     

肺与大肠相表里的微生态学解释

"肺与大肠相表里"、"肺在志为悲(忧)"均是传统中医所特有的思维,现代临床实践也发现肠道疾病与肺部疾病常相伴而发,而情志失调常为肺肠疾病的诱因。但没有物质基础的经脉如何联系肺与肠,用经脉络属或是五行理论来解释的"肺在志为悲(忧)"观点有没有明确的物质基础仍有待研究。目前各项研究发现肺与大肠在解剖及生理病理过程方面存在相似性,而菌群在肺—肠联系中起着重要的作用,很可能是经脉联系肺肠的物质基础之一,随着对肠道菌群研究的进一步深入,其与抑郁症等情志障碍疾病的潜在关系被逐渐揭示,也让"肺在志为悲(忧)"的观点获得认同和深化,借助最新研究成果深度认识理论术语与客观实在的关系,是中医发展的必由之路。     

低聚果糖对慢性应激小鼠抑郁样行为及 肠道菌群的影响

目的探讨低聚果糖(FOS)对慢性应激小鼠的抑郁样行为及肠道菌群的影响。方法选取8周龄健康雄性ICR小鼠随机分成3组,C组小鼠每天给予正常护理,S组和SF组小鼠每天随机给予1～2种应激源,持续8周,SF组小鼠在应激造模的同时经食物补充FOS。在造模4周和8周后,分别通过强迫游泳、蔗糖偏好试验评估各组小鼠抑郁样行为。造模结束后通过Western blot试验检测小鼠大脑皮层内糖皮质激素受体(GR)的表达,并收集结肠内容物进行16SrDNA扩增子测序分析。结果应激造模8周后,C、S和SF三组小鼠的肠道菌群组成存在明显差异;与C组相比,S组小鼠强迫游泳的不动时间显著增加(t=3.970,P=0.0009),蔗糖偏好率显著降低(t=3.890,P=0.0011),脑内GR的表达显著降低(t=4.311,P=0.0125);与S组相比,SF组小鼠强迫游泳的不动时间显著缩短(t=3.495,P=0.0026),蔗糖偏好率和脑内GR表达有增加趋势。结论益生元FOS可调节肠道菌群,改善慢性应激诱发的精神情绪异常。     

Effects of Depressed Affect on Diurnal and Ultradian Variations in Mood in a Healthy Sample

The study investigated diurnal and ultradian variations in cheerful and depressed mood in a healthy sample, and examined whether these variations were related to severity of depressed affect. Thirty employed volunteers used a pocket computer to complete self-rating scales of depression and cheerfulness every 2 h for 14 days except during sleep periods. They also completed the Beck Depression Inventory (BDI) and the General Health Questionnaire (GHQ). Analysis of variance of depressed mood showed a significant interaction between time of day and BDI/GHQ, in which only the mood of the high BDI/GHQ groups got worse during the day. The low BDI group showed a diurnal variation in cheerful mood in which mood was at its best in the early evening. Cosinor and “binfit” analysis of raw and residual time-series showed that more than half of the participants had significant fitting ultradian rhythms in mood in the range 3-9 h. However, only the number of significant fits for residual cheerful mood was substantially above the level of chance. The amplitudes of the ultradian rhythms in raw depressed mood were greater in participants scoring higher on the BDI/GHQ scales, but this seemed to reflect an increase in serial dependency between depressed mood states. The results are discussed in relation to circadian rhythms in mood and depression.     

Endogenous opiates: 1994

This article is the 17th installment of our annual review of research concerning the opiate system. It includes papers published during 1994 involving the behavioral, nonanalgesic, effects of the endogenous opiate peptides. The specific topics covered this year include stress; tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunological responses; and other behaviors.     

大鼠内侧前额叶皮质内ERK1/2 活化参与脊髓损伤后抑郁情绪

目的:观察细胞外信号调节激酶1/2(ERK1/2)的活化在脊髓损伤引起抑郁中的作用。方法:应用Western blot和行为药理学方法,观察脊髓损伤后(SCI)大鼠内侧前额叶皮质内(mPFC)ERK1/2及磷酸化-ERK1/2(p-ERK1/2)的表达情况及ERK1/2磷酸化抑制剂U0126对抑郁样行为的影响。结果:脊髓损伤后的第2天到第8周,SCI模型大鼠的BBB评分均显著低于假手术组,差异具有统计学意义(p0.05)。脊髓损伤后8周-12周,SCI模型大鼠强迫游泳不动时间与假手术组相比明显缩短,mPFC内pERK1/2蛋白表达水平明显升高,总ERK 1/2的蛋白水平则未见组间差异,而给予U0126的大鼠的不动时间与给药之前相比明显延长增加,mPFC内pERK1/2蛋白表达水平较SCI模型大鼠明显降低,差异均具有统计学意义(P0.05)。结论:内侧前额叶皮质内ERK1/2的激活参与了脊髓损伤后引起的突触可塑性,在相关的抑郁样行为的产生中发挥了重要的作用。