Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed.     

Effects of Wellness Programs in Family Medicine

The objective of this research was to determine the effects of wellness programs on quality of life and utilization in an academic family medicine practice in two small controlled studies. One offered stress management and problem solving; the second offered a broader wellness intervention. Outcome measures consisted of scores on the Beck Anxiety Inventory, Hamilton Depression Inventory, CES-D (depression), Health Related Quality of Life, SF-12, and the number of office visits in 6 months. Subjects were randomly assigned to intervention or control groups. Statistical analysis compared pre-test and post-test values of the dependent variables between groups. In study one, where the focus was on relaxation, significant differences between groups were observed in anxiety at post-test (p < .03); the intervention group had lower anxiety levels. In study two which had a more general focus, significant group differences were found in days of poor mental health and number of days of depressed mood; the intervention group had fewer days of poor mental health (p < .05) and depression (p < .05) at post-test. No differences were found in utilization in either study. Based on the results of this research, short term wellness programs can be implemented in family practice and are effective in improving quality of life, but not in deceasing utilization in family practice patients. Matching the design of the program to specific patient needs may increase retention and effectiveness.     

Underlying mechanisms mediating the antidepressant effects of estrogens

Background

There is an increased risk for depressive symptoms and affective disorders in individuals who experience drastic drops or fluctuations of gonadal hormones. Moreover, clinical studies indicate that estrogens have the potential to be effective in treating depression.

Scope of the review

Possible underlying mechanisms for the antidepressant activity of estrogens are reviewed and discussed.

Major conclusions

Estrogens exert their antidepressant activity via a multimodal mechanism of action by regulating several pathways and functions associated with antidepressive effects. Estrogens increase serotonergic activity by regulating the synthesis and degradation of serotonin, as well as spontaneous firing of the serotonergic neurons in the raphe nuclei. Both pre- and postsynaptic serotonin receptors are shown to be regulated by estrogens. In addition, estrogens are neurotrophic and promote neuroplasticity and neurogenesis. Similar effects are also observed after treatment with current antidepressant therapies. However in stark contrast to current therapies which must be administered chronically to produce an effect, the responses to estrogens are often observed after a single dose. Many of these estrogenic effects, including antidepressant and anxiolytic responses in behavioral models in rodents, appear to be mediated via the estrogen receptor β subtype.

General significance

The rapid onset of action combined with the multifactorial mechanism of action of estrogens indicates that estrogen treatment could complement currently available therapies for depression. Considering safety aspects, selective estrogen receptor β agonists would probably be the optimal estrogenic therapy.     

Prefrontal morphology, 5‐HTTLPR polymorphism and biased attention for emotional stimuli

Biased attention for emotional stimuli has been associated with vulnerability to psychopathology. This study examines the neural substrates of biased attention. Twenty‐three adult women completed high‐resolution structural imaging followed by a standard behavioral measure of biased attention (i.e. spatial cueing task). Participants were also genotyped for the serotonin transporter‐linked promoter region (5‐HTTLPR) gene. Results indicated that lateral prefrontal cortex (lPFC) morphology was inversely associated with maintained attention for positive and negative stimuli, but only among short 5‐HTTLPR allele carriers. No such associations were observed for the medial prefrontal cortex (mPFC) or the amygdala. Results from this study suggest that brain regions involved in cognitive control of emotion are also associated with attentional biases for emotion stimuli among short 5‐HTTLPR allele carriers.     

Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results

It has been hypothesised that polyunsaturated fatty acids (PUFA) play an important role in the aetiology of schizophrenia and depression. Evidence supporting this hypothesis for schizophrenia includes abnormal brain phospholipid turnover shown by 31P Magnetic Resonance Spectroscopy, increased levels of phospholipase A2, reduced niacin skin flush response, abnormal electroretinogram, and reduced cell membrane levels of n-3 and n-6 PUFA. In depression, there is strong epidemiological evidence that fish consumption reduces risk of becoming depressed and evidence that cell membrane levels of n-3 PUFA are reduced. Four out of five placebo-controlled double- blind trials of eicosapentaenoic acid (EPA) in the treatment of schizophrenia have given positive findings. In depression, two placebo-controlled trials have shown a strong therapeutic effect of ethyl-EPA added to existing medication. The mode of action of EPA is currently not known, but recent evidence suggests that arachidonic acid (AA) if of particular importance in schizophrenia and that clinical improvement in schizophrenic patients using EPA treatment correlates with changes in AA.     

Endogenous opiates: 1993

This paper is the sixteenth installment of our annual review of research concerning the opiate system. It is restricted to papers published during 1993 that concern the behavioral effects of the endogenous opiate peptides, and does not include papers dealing only with their analgesic properties. The specific topics 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; development; immunological responses; and other behaviors.     

肠道菌群失调与抑郁症合并冠心病预后的相关性

摘要 目的：探讨肠道菌群失调与抑郁症合并冠心病的相关性,并分析肠道菌群失调对抑郁症合并冠心病预后的预测价值。方法：选取我院2021年6月到2022年5月收治的80例抑郁症患者作为研究对象,将单纯抑郁症的49例患者分为抑郁症组,将合并冠心病的31例患者分为l联合组,另选取同期来我院体检的40名健康者分为对照组,对比三组患者肠道菌群情况,应用Spearman相关分析分析肠道菌群失调与抑郁症合并冠心病的相关性。随后,对31例抑郁症合并冠心病患者进行随访,将其分为预后良好组（n=21）和预后不良组（n=10）,对比两组患者临床一般情况与肠道菌群情况,应用logistic回归分析分析肠道菌群对抑郁症合并冠心病的预后预测价值。结果：三组患者拟杆菌情况无明显差异（P＞0.05）,肠杆菌、肠球菌、双歧杆菌、乳杆菌和双歧杆菌属与肠杆菌科细菌数量比（B/E）值对比差异显著,l联合组肠杆菌、肠球菌明显高于抑郁症组和对照组,双歧杆菌、乳杆菌、B/E值明显低于抑郁症组和对照组（P＜0.05）;Spearman相关分析结果显示：肠道菌群失调中拟杆菌水平与抑郁症合并冠心病无明显相关性（P＞0.05）,肠道菌群失调中肠杆菌、肠球菌水平与抑郁症合并冠心病呈正相关,与双歧杆菌、乳杆菌和双歧杆菌属与肠杆菌科细菌数量的对数值比（B/E）值呈负相关（P＜0.05）;预后良好组与预后不良组、年龄、BMI、合并基础疾病、hs-cTnT、NT-proBNP、NT-proBNP、PHQ-9评分、拟杆菌对比无明显差异（P＞0.05）,hs-CRP、肠杆菌、肠球菌、双歧杆菌、乳杆菌、B/E值对比差异显著（P＜0.05）;logistic回归分析结果表明：只有hs-CRP和B/E值菌群失调对于抑郁症合并冠心病的预后具有独立预测价值（P＜0.05）。结论：抑郁症合并冠心病患者较单一抑郁症和健康者来说肠道菌群比例出现失调,且肠道菌群失调与抑郁症合并冠心病呈明显相关性,应用B/E 值可对抑郁症合并冠心病患者预后情况进行预测。     

血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值分析

摘要 目的：分析血清胃促生长素（ghrelin）、Nod样受体热蛋白结构域相关蛋白3（NLRP3）对老年抑郁症患者认知功能损害的诊断价值。方法：选择2020年1月至2021年10月在我院接受诊治的老年抑郁症患者90例作为抑郁症组,另选取同期精神健康老年志愿者50例作为对照组。根据抑郁症病情严重程度将老年抑郁症患者分为轻度组（n=32）、中度组（n=30）、重度组（n=28）,比较不同分组研究对象血清ghrelin、NLRP3水平变化。另根据老年抑郁症患者是否发生认知功能损害分为认知功能损害组和认知功能未损害组,收集患者一般人口学及临床资料,分析影响老年抑郁症患者认知功能发生损害的危险因素。采用受试者工作特征（ROC）曲线分析血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值。结果：重度组血清NLRP3炎症小体水平明显高于中度组,中度组血清NLRP3炎症小体水平明显高于轻度组,轻度组血清NLRP3炎症小体水平明显高于对照组（P<0.05）;重度组血清ghrelin水平明显低于中度组,中度组血清ghrelin水平明显低于轻度组,轻度组血清ghrelin水平明显低于对照组（P<0.05）。多因素Logistic回归分析结果显示,重大生活事件（意外事故、破产、至亲去世等）、合并糖尿病、血清ghrelin水平、独居、血清NLRP3炎症小体水平以及社会支持是老年抑郁症患者认知功能损害的影响因素（P<0.05）。血清NLRP3炎症小体、ghrelin单独以及联合诊断老年抑郁症患者认知功能损害的曲线下面积AUC（0.95CI）分别为0.723（0.506～0.922）、0.782（0.619～0.917）、0.863（0.721～0.981）。结论：血清NLRP3炎症小体水平在老年抑郁症患者中呈高表达、ghrelin水平呈现低表达,二者均是老年抑郁症患者认知功能损害的影响因素,且联合检测二者水平可辅助诊断老年抑郁症患者认知功能损害。     

血清5-HT、Obestatin、APRIL与老年脑卒中患者神经功能的相关性及对卒中后抑郁的预测价值

摘要 目的：探讨血清5-羟色胺（5-HT）、肥胖抑制素（Obestatin）、增殖诱导配体（APRIL）与老年脑卒中患者神经功能的相关性及对卒中后抑郁（PSD）的预测价值。方法：选择2019年5月至2022年5月内蒙自治区人民医院收治的老年脑卒中患者120例为研究对象。入院时采集血样本,采用酶联免疫吸附法（ELISA）检测血清5-HT、Obestatin和APRIL水平。患者出院后随访6个月,根据是否发生PSD分为PSD组和非PSD组,比较两组血清5-HT、Obestatin、APRIL水平。采用Pearson相关分析法分析5-HT、Obestatin、APRIL与美国国立卫生研究院卒中量表（NIHSS）的相关性;采用多因素Logistic回归模型分析PSD的影响因素;采用受试者工作特征（ROC）曲线分析血清5-HT、Obestatin联合APRIL对老年脑卒中患者出院后PSD的预测价值。结果：PSD组血清5-HT低于非PSD组（P＜0.05）,血清Obestatin、APRIL和NIHSS评分高于非PSD组（P＜0.05）。血清5-HT与NIHSS评分呈负相关（P＜0.05）;血清Obestatin、APRIL与NIHSS评分呈正相关（P＜0.05）。单因素分析显示,老年脑卒中患者出院后PSD与体质量指数（BMI）、吸烟史、饮酒史有关（P＜0.05）。多因素Logistic回归分析显示,血清Obestatin、APRIL及NIHSS评分升高是脑卒中患者出院后发生PSD的危险因素（P＜0.05）,血清5-HT升高是其保护因素（P＜0.05）。ROC曲线分析结果显示,血清5-HT、Obestatin、APRIL及联合检测对预测PSD的曲线下面积（AUC）分别为0.735（0.483～0.978）、0.765（0.595～0.918）、0.707（0.464～0.954）、0.867（0.742～0.972）,联合检测的预测效能优于各指标单独检测。结论：血清5-HT水平降低、Obestatin、APRIL水平及NIHSS评分升高是老年脑卒中患者出院后发生PSD的独立危险因素,还可导致神经功能损伤,血清5-HT、Obestatin和APRIL可预测老年脑卒中患者出院后PSD,且联合预测价值更高。