Toll-like receptor 2 (TLR2)-deficiency impairs male mouse recovery from a depression-like state

Major depression is a prevalent, debilitating disease, yet therapeutic interventions for depression are frequently inadequate. Many clinical and pre-clinical studies have demonstrated that depression is associated with aberrant activation of the inflammatory system, raising the possibility that reducing inflammation may provide antidepressant effects. Using the learned helplessness mouse model, we tested if susceptibility or recovery were affected by deficiency in either of two receptors that initiate inflammatory signaling, Toll-like receptor-4 (TLR4) and TLR2, using knockout male mice. TLR4^-/- mice displayed a strong resistance to learned helplessness, confirming that blocking inflammatory signaling through TLR4 provides robust protection against this depression-like behavior. Surprisingly, TLR2^-/- mice displayed increased susceptibility to learned helplessness, indicating that TLR2-mediated signaling counteracts susceptibility. TLR2-mediated signaling also promotes recovery, as TLR2^-/- mice demonstrated a severe impairment in recovery from learned helplessness. That TLR2 actually protects from learned helplessness was further verified by the finding that administration of the TLR2 agonist Pam3CSK4 reduced susceptibility to learned helplessness. Treatment with Pam3CSK4 also reversed chronic restraint stress-induced impaired sociability and impaired learning in the novel object recognition paradigm, demonstrating that TLR2 stimulation can protect from multiple impairments caused by stress. In summary, these results demonstrate that TLR2-mediated signaling provides a counter-signal to oppose deleterious effects of stress that may be related to depression, and indicate that TLR2 and TLR4 act oppositely to balance mood-relevant responses to stress.     

Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons

BackgroundOur previous study reports the causal role of high mobility group box 1 (HMGB1) in the development of depression; and we find glycyrrhizic acid (GZA) can be a potential treatment for major depressive disorder (MDD) considering its inhibition of HMGB1 activity. This study aims to further explore the exact cell types that release HMGB1 in the hippocampus.MethodsWe detected the effects of microglia conditioned medium on primary astrocytes and neurons. The effects of minocycline on depressive-like behaviors were tested in BABLB/c mice after four weeks of chronic unpredictable mild stress (CUMS) exposure. Furthermore, the immunofluorescence (IF) assays, hematoxylin-eosin (HE) and TUNEL staining were used to observe hippocampal slices to evaluate the release of HMGB1. The cytoplasmic translocations of HMGB1 protein were assayed by western-blot.ResultsExposure to CUMS caused an active release of HMGB1 from microglia and neurons in the hippocampus. After minocycline administration for inhibiting the activation of microglia, both microglia and neurons reduced the release of HMGB1 and the protein level of central and peripheral HMGB1 recovered accordingly. Along with blocking the release of HMGB1, behavioral and cognitive deficits induced by CUMS were improved significantly by minocycline. In addition, the supernatant of primary microglia stimulated the secretion of HMGB1 in primary neurons, not in astrocytes, at 24 h after 4 h-LPS treatment.ConclusionAll the evidence supported our hypotheses that microglia and neurons are the main cell sources of HMGB1 release under CUMS condition, and that the release of HMGB1 by microglia may play an important role in the development of depressive-like behavior.     

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.     

The Covid-19 infection: An opportunity to develop systematic vitamin D supplementation in psychiatry

Psychiatric patients are at risk of hypovitaminosis D and Covid-19-related mortality. In addition to the mental health benefits, vitamin D supplementation may be potentially effective in preventing severe forms of Covid-19 infections. Vitamin D supplementation is not necessary and is not reimbursed in France for this indication. A monthly supplementation of 50,000 IU may be sufficient in most cases. Double the dose is recommended for obese patients. The risk of renal lithiasis is not increased at these doses, even when supplemented in a patient without vitamin D deficiency. The Covid-19 crisis is an opportunity to disseminate vitamin D supplementation in psychiatric patients, as it has been shown to be effective in other respiratory diseases such as mild upper respiratory tract infections and influenza.     

Health-related Quality of Life for Abiraterone Plus Prednisone Versus Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer: Results from a Phase II Randomized Trial

BackgroundAbiraterone and enzalutamide are associated with side effects that may impair health-related quality of life (HRQoL).ObjectiveTo assess patient-reported HRQoL, depression symptoms, and cognitive function for abiraterone versus enzalutamide.Design, setting, and participantsWe randomized 202 patients in a phase II study of abiraterone versus enzalutamide for first-line treatment of metastatic castration-resistant prostate cancer (ClinicalTrials.gov: NCT02125357).InterventionPatients completed Functional Assessment of Cancer Therapy—Prostate (FACT-P) and Patient Health Questionnaire-9 (PHQ-9) questionnaires, and Montreal Cognitive Assessment (MoCA) cognitive assessments at baseline and on treatment.Outcome measurements and statistical analysisTo compare the change in FACT-P scores over time between treatment arms, we used a mixed model for repeated measures (MMRM). For FACT-P domains where there was an interaction between the treatment arm and age, we constructed separate models for patients aged <75 and ≥75 yr. We compared the proportion of patients with clinically meaningful change from baseline for FACT-P, and the proportion of patients with an abnormal score and median change from baseline for PHQ-9 and MoCA using Fisher's exact test and Mann-Whitney U test.Results and limitationsIn the MMRM analysis, there was a positive test for interaction in the treatment arm by age for total FACT-P (p = 0.048). FACT-P change from baseline over time was better for abiraterone than for enzalutamide in the ≥75-yr model (p = 0.003), with no difference in the <75-yr model (p > 0.9). A higher proportion of patients experienced clinically meaningful worsening with enzalutamide for the physical and functional well-being domains (37% vs 21%, p = 0.013; 39% vs 23%, p = 0.015). The distribution of change in PHQ-9 scores from baseline favored abiraterone at weeks 4, 8, and 12. These analyses were not prespecified, and results should be considered to be hypothesis generating.ConclusionsPatient-reported outcomes favored abiraterone compared with enzalutamide with differences in FACT-P HRQoL and PHQ-9 depression scores. Differences in the total FACT-P scores were seen only in the elderly patient subgroup.Patient summaryIn this report, we examined the change in patient-reported quality-of-life scores from the start of treatment over time for patients treated with abiraterone versus enzalutamide for metastatic castration-resistant prostate cancer. We found that elderly patients treated with abiraterone had better quality of life over time, with no difference between treatments for the younger subgroup of patients.     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

基于文献研究PCI术后伴焦虑抑郁中医药治疗进展

冠心病PCI术后伴焦虑抑郁状态患者逐年增多,严重影响患者预后及生命质量,因此,我们需要将心理干预与心血管疾病的防治置于同等地位。对此,系统收集和整理冠心病PCI术后伴心理问题的相关文献,共计28篇文献,有完整处方名称25首,没有处方名称自拟方3首,涉及中药15类79种中药,治疗患者2 099例。使用频率较多的中药种类:补虚药、理气药、安神药、活血化瘀药、清热药。28篇文献中应用随机对照试验文献26篇,心理因素评估最常用的方式为汉密尔顿焦虑量表及汉密尔顿抑郁量表。     

持续个性化护理干预对老年帕金森病患者抑郁症状及运动功能的效果分析

目的:探讨持续个性化护理干预对老年帕金森病患者抑郁症状及运动功能的效果分析。方法:选择2018年1月-2019年1月治疗的老年帕金森病患者60例作为对象,随机数字表法分为对照组(30例)和观察组(30例)。对照组给予常规护理,观察组给予持续个性化护理干预,治疗后对患者效果进行评估,比较两组饮食、运动和服药行为以及由汉密顿抑郁量表(Hamilton Depression Scale,HAMD)评分、汉密顿焦虑量表(Hamilton Anxiety Scale,HAMA)评分。结果:两组干预后评分均无统计学意义(P>0.05);研究组干预后1个月饮食、运动、服药行为评分均高于对照组(P<0.05);两组HAMD、HAMA评分护理后均比护理前有明显下降,比较差异有统计学意义(P<0.05)。观察组护理后HAMD、HAMA评分低于对照组,组间比较差异有统计学意义(P<0.05)。结论:将持续个性化护理干预用于老年帕金森病患者护理中护理效果好,可缓解患者的不良心理情绪,有效降低患者的情绪焦虑、抑郁的发生率,值得推广应用。     

部队救援人员认知情绪调节与抑郁的早期筛查模型

目的调查某部1324名救援人员认知情绪调节策略及抑郁自评结果,探索认知情绪调节策略与抑郁的预测模型。方法采取整群抽样方式,现场调查某部救援人员共1324名,采用患者健康问卷抑郁量表(PHQ-9)、认知情绪调节量表(CERQ)进行调查。运用二元logistic回归分析建立抑郁筛查预测模型。结果某部救援人员抑郁筛查阳性率为11.3%,筛出抑郁状态150名。Logistic回归分析结果显示,灾难化(P=0.000)、积极重新评价(P=0.001)、接受(P=0.000)三种认知情绪调节策略可显著预测抑郁筛查阳性,OR及95%CI分别为:1.509(1.348~1.689)、1.197(1.079~1.329)及0.817(0.739~0.903)。灾难化、接受与抑郁情绪呈正相关。结论灾难化、接受积极重新评价这三种认知情绪调节策略对该部救援人员抑郁自评结果有预测作用。     

Comprendre les troubles du sommeil de patients adultes atteints d’une maladie de Crohn pris en charge en ambulatoire

ObjectivesResearch has shown that sleep disturbances can negatively influence the progression of chronic inflammatory diseases, including chronic inflammatory bowel disease (IBD). More specifically, poor sleep quality is strongly related to the clinical activity of the disease. Nevertheless, some patients suffer from sleep disorders even when the disease is clinically inactive. Psychological factors, such as depression and anxiety, are also known to contribute to poor sleep quality. Depression and anxiety are common in chronic diseases. In addition, while the link between depression or anxiety and sleep disorders is well-known, the link between sleep disorders and inflammation has only been studied recently. Sleep studies in IBD patients have generally excluded patients with clinically diagnosed depression or anxiety in order to neutralize their effects on the relationship between inflammation and sleep disorders. Nevertheless, there is no consensus on the relationship between depression and anxiety and the clinical activity of the disease. When a patient with chronic inflammatory bowel disease (Crohn's disease here) complains of fatigue or poor sleep, the subjective aspects of these complaints therefore lead the clinician to consider them simply as: a characteristic of IBD, exhaustion related to the chronicity of the disease, unsatisfactory sleep quality, a manifestation of a depressive mood, or a consequence of an anxious state. When a patient reports a subjective complaint of poor sleep or fatigue in a complex, multi-determined clinical situation, it can thus be difficult to identify its most likely cause and to establish the best possible therapeutic intervention.Patients, materials and methodsThe aim of this work was to determine which element (disease activity, inflammation, depression, anxiety) is most closely related to sleep disorders in patients with Crohn's disease (CD) referred for outpatient psychological assessment. Ninety-seven patients with CD participated in this study. Their mean age was 34.70 (± 10.85) years. They were asked about their sleep (IQSP, ISI, ESD) and mood (HADS). They also provided details of clinical disease activity (Harvey–Bradshaw Index) and inflammation (CRP). In order to determine the nature and extent of the relationship between the variables, Spearman correlation coefficients were calculated, supplemented by multiple regression analyses to determine the variables that could explain the sleep disorders.ResultsThe results show that sleep quality (IQSP) was significantly predicted by the Harvey–Bradshaw score (β = 0.21; β standardized = 0.24; t = 2.6; P = 0.01) and depression (β = 0.45; β standardized = 0.41; t = 4.55; P < 0.001). The Harvey–Bradshaw score (β = 26; β standardized = 2; t = 2.27; P = 0.026) and depression score (β = 75; β standardized = 47; t = 5.34; P < 0.001) were related to the insomnia score (ISI). Finally, daytime sleepiness (DSA) was predicted by the depression score (β = 42; β standardized = 432; t = 3.17; P = 0.002) and by the CRP (β = − 0.05; β standardized = − 0.21; t = − 2.13; P = 0.036). The results show that the severity of clinical activity of the disease was associated with poor sleep quality and insomnia. However, there was a stronger association between the intensity of depression and sleep disturbances than between these variables and clinical disease activity. It therefore seems important that sleep disorders and their management should be considered first from the perspective of depression. However, it is important that CD is not assumed to be the sole cause of depression: other factors (dispositional or situational) should also be taken into consideration. Nevertheless, while our results show a weaker link between inflammation and sleep disorders than other studies, they confirm the link between sleep disorders and disease activity.ConclusionsIn order to predict the likelihood and nature of relapses, it seems important that future research should take into account not only disease activity and inflammation, but also disorders of arousal and nocturnal awakenings experienced by the patient.