双相障碍与单相抑郁患者雌二醇和催乳素水平对照研究

目的探讨双相障碍、单相抑郁患者与健康人群之间雌二醇、催乳素水平差异以及性激素水平与躁狂、抑郁症状之间的相关性。方法选取2014年1月-2015年5月收住北京回龙观医院的符合《国际疾病分类(第10版)》(ICD-10)双相情感障碍、抑郁发作诊断标准的患者99例(男性55例,女性44例)。采用汉密尔顿抑郁量表24项版(HAMD-24)、蒙哥马利-艾森贝格抑郁量表(MADRS)评估抑郁症状,采用贝克-拉范森躁狂量表(BRMS)评估躁狂症状;选取与患者组性别、年龄及受教育程度相匹配的42例健康人作为对照组。采用化学发光免疫分析法检测研究对象周围血中雌二醇、催乳素水平。结果催乳素水平在双相障碍组、单相抑郁组以及健康对照组之间差异有统计学意义(F=6.575,P0.05),而三组雌二醇水平差异无统计学意义(P0.05),催乳素水平与BRMS评分呈正相关(r=0.361,P=0.033),雌二醇水平与抑郁症状及躁狂症状评分相关均不显著(P0.05)。结论心境障碍患者存在性激素水平的改变;性激素水平与情感症状严重程度存在相关性。     

双相障碍抑郁发作患者治疗前后E2、PRL、CRP水平变化及其与疗效的关系

目的 探讨双相障碍（BD）抑郁发作患者治疗前后雌二醇（E2）、催乳素（PRL）、C反应蛋白（CRP）水平变化及与疗效的关系。方法 回顾性分析2019年9月～2021年9月本院收治BD抑郁发作患者116例为BD组,另选取同期健康体检者58例为对照组。检测两组E2、PRL、CRP水平,以ROC曲线评估E2、PRL、CRP水平对疗效的预测价值。结果 BD组患者治疗前E2水平显著低于对照组,CRP水平显著高于对照组（P<0.05）,PRL水平差异无统计学意义（P>0.05）;而BD组患者治疗后E2、PRL及CRP水平与对照组比较差异均无统计学意义（P>0.05）。BD抑郁发作患者治疗总有效率为81.90%。多因素分析显示,病程≥6个月、发作次数≥5次、抑郁、E2水平升高、CRP水平降低均为BD抑郁发作患者疗效的影响因素（P<0.05）。ROC结果显示,E2、CRP水平预测疗效的AUC分别为0.795、0.986。结论 血清E2、CRP与BD抑郁发作密切相关,二者可能可以作为BD抑郁发作疗效的预测指标。     

双相情感障碍血清尿酸水平研究

目的探讨双相情感障碍患者血清尿酸(uric acid,UA)水平变化及其临床意义。方法纳入双相情感障碍患者126例(躁狂发作77例,抑郁发作49例)、首发精神分裂症患者69例和正常对照126名,测定其血清UA水平,并采用杨氏躁狂量表(Young mania rating scale,YMRS)和汉密尔顿抑郁量表(Hamilton depressionscale,HAMD)评定双相情感障碍患者症状。结果双相情感障碍组血清UA水平[(349.34±107.21)μmol/L]高于精神分裂症组[(319.71±84.48)μmol/L]和对照组[(280.94±71.90)μmol/L],差异有统计学意义(P0.01);躁狂发作患者UA水平高于抑郁发作患者[(366.45±104.01)μmol/L vs.(322.45±107.69)μmol/L],且二者均高于对照组(P0.01);双相情感障碍患者中是否使用精神科药物的亚组间UA水平无统计学差异(P0.05)。双相情感障碍患者血清UA水平与YMRS、HAMD分数线性相关均无统计学意义(P0.05)。结论双相情感障碍患者血清UA水平升高,血清UA水平升高可能是双相情感障碍的一个生物标记物。     

双相情感障碍的治疗现状

本对近年来国外有关双相情感障碍之治疗的研究与观点进行介绍。     

双相情感障碍混合发作血清细胞因子水平研究

目的：比较双相情感障碍混合发作与躁狂发作及抑郁发作患者之间血清细胞因子的水平。方法：采用酶联免疫吸附法测定38例双相情感障碍混合发作患者（混合组）、54例躁狂发作患者（躁狂组）、47例抑郁发作患者（抑郁组）及38名正常人（对照组）血清白介素-1（IL-1β）、白介素-2（IL-2）及白介素-6（IL-6）的浓度;混合组患者于治疗前和治疗8周进行Hamilton抑郁量表（HAMD-24）和Young躁狂量表（YMRS）评定。结果：混合组IL-1β浓度显著高于躁狂组及抑郁组（P〈0.01）,但与对照组差异无统计学意义（P〉0.05）。混合组IL-2浓度与躁狂组、抑郁组及对照组之间差异均无统计学意义（P〉0.05）。混合组IL-6浓度显著高于躁狂组、抑郁组及对照组（P〈0.001）。混合组IL-6浓度治疗8周后较治疗前显著下降（t=3.372,P〈0.01）,与对照组比较差异无统计学意义（t=1.823,P〉0.05）。混合组治疗前后IL-6浓度差值与HAMD-24、YMRS减分率之间均无显著相关（r分别=-0.211、-0.100,P均〉0.05）。结论：双相情感障碍混合发作可能存在IL-6诱导的免疫功能异常,有不同于双相情感障碍躁狂发作及抑郁发作的生物学特征。     

双相情感障碍的最新研究进展

本文就双相情感障碍的定义、分类和治疗等方面的最新研究进展进行了概述。     

双相情感障碍抑郁相与单相抑郁发作临床分析

目的:对双相情感障碍抑郁相和单相抑郁发作进行临床分析。方法:对双相情感障碍抑郁相和单相抑郁发作患者各30例进行临床分析。结果:双相情感障碍抑郁相有如下特点:①发病年龄早;②女性多见;③具有“精力过盛”性人格;④一级亲属中有双相障碍的家族史;⑤症状多为非典型抑郁发作或伴有精神病性症状。结论:如首次抑郁发作的症状符合以上特点,则可能以后发展为双相情感障碍,应使用足量心境稳定剂,谨慎使用抗抑郁剂,以免转为躁狂发作。     

双相I型障碍躁狂发作患者高尿酸血症发生率及其影响因素的研究

目的：探讨双相 I 型躁狂发作患者高尿酸血症（HUA）的发生率及其影响因素。方法：检测77例双相 I 型躁狂发作住院患者（患者组）和77名健康对照者（正常对照组）血清尿酸水平,同时检测体质量、腰臀比、血压及三酰甘油（TG）水平。结果：患者组 HUA 的发生率28.6%（22例）显著高于正常对照组7.8%（6例）（χ2=11.18,P <0.01）。平均血清尿酸水平患者组（365.19±103.45）μmol/ L显著高于正常对照组（301.77±76.04）μmol/ L,差异有统计学意义（F =25.70,P <0.01）;男性血清尿酸水平高于女性[（381.43±99.02）vs（291.38±70.33）]μmol/ L（F =50.08,P <0.01）。相关分析显示,患者组中性别与血清尿酸水平呈负相关（r =-0.56,P <0.01）;TG 水平与血清尿酸水平呈正相关（r =0.419,P <0.01）。结论：双相 I 型障碍躁狂发作患者 HUA 发生率增加并与性别、血清 TG 水平相关。     

我国软双相障碍研究现状与进展

1软双相的概念与意义 软双相是一个过渡性诊断概念,它是指一种双相障碍诊断建立之前的抑郁状态,因为没有躁狂的存在而称为“软”的双相。它还称为：假性单相的双相障碍（pseudo—unipolar bipolar disorder）、假单相障碍（false unipolar disorder）,也就是“没有躁狂的”的双相障碍。但是这些软双相具有某些特征,这些特征决定了它们在将来某个特定的时间就很有可能成为或发展为真正的双相障碍。     

双相情感障碍神经内分泌功能对照研究

目的:探讨双相情感障碍混合发作与躁狂发作患者神经内分泌功能. 方法:以放射免疫方法测定23例双相情感障碍混合发作患者(混合组)、54例躁狂发作患者(躁狂组)和38名正常人(对照组)血浆皮质醇(Cor)、促肾上腺皮质激素(ACTH)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)及促甲状腺激素(TSH)的浓度. 结果:混合组血浆Cor及ACTH浓度均明显高于对照组(P<0.05或P<0.001);而躁狂组与对照组血浆Cor浓度比较差异无统计学意义,但ACTH浓度明显高于对照组(P<0.001);混合组血浆Cor浓度明显高于躁狂组(P<0.05),但ACTH浓度两组间差异无统计学意义.与对照组相比,混合组T3浓度显著较高,T4浓度显著较低(P<0.05),而TSH浓度两组间差异无统计学意义(P>0.05);躁狂组T3浓度显著高于对照组(P<0.001),TSH浓度显著低于对照组(P<0.01);混合组T3、T4浓度均显著低于躁狂组(P<0.05或P<0.01),TSH浓度明显高于躁狂组(P<0.05). 结论:双相情感障碍混合发作及躁狂发作均存在神经内分泌功能的改变,但二者的改变并不相同.     

抑郁症患者急性期治疗前后临床症状和工作记忆变化及两者的相关性

目的 探讨抑郁症患者急性期治疗前后临床症状与工作记忆的变化及两者的相关性。 方法 招募 2017 年 7 月至 2019 年 12 月就诊于首都医科大学附属北京安定医院门诊的抑郁症患者,均采 用草酸艾司西酞普兰 10～20 mg/d 治疗,随访 12 周。基线及 12 周末采用自定顺序指示任务（SOPT）和延 迟回忆任务评估工作记忆,采用汉密尔顿抑郁量表 17 项（HAMD-17）量表评估临床症状。采用 χ2 检验、 Wilcoxon 秩和检验及 Spearman 相关分析比较各指标的变化及两者的相关性。结果 共招募抑郁症患者 139例,其中73例完成12周随访。基线工作记忆精度在K2负载条件下与焦虑症状具有相关性（r=-0.171, P＜ 0.05）。工作记忆容量与焦虑症状具有相关性（r=-0.189,P＜ 0.05）。12 周末 43 例（58.9%）完全缓解; 缓解组的 HAMD-17 减分值［16.00（12.00,19.00）分］与未缓解组［8.00（4.00,11.00）分］比较,差异有统 计学意义（P＜ 0.05）。缓解组与未缓解组的抑郁症状［7.00（6.00,9.00）分比 5.00（3.00,5.00）分］、焦虑症 状［4.00（3.00,6.00）分比 2.00（1.00,4.00）分］、睡眠症状［1.00（0,3.00）分比 1.00（0,2.00）分］、躯体症状［2.00 （1.00,3.00）分比 1.00（0,3.00）分］的减分值比较,差异均有统计学意义（P＜ 0.05）;随访 12 周后,HAMD- 17 总分及各维度变化值与工作记忆各维度变化值无相关性（P＞ 0.05）。结论 抑郁症患者的焦虑症状 与工作记忆相关,急性期治疗前后临床症状及工作记忆变化无相关性。     

Effects of short and long-term lithium treatment on serum prolactin levels in patients with bipolar affective disorder

1. In this study, the authors sought to test the hypothesis that Li (lithium) treatment can induce alterations in PRL (prolactin) secretion in euthymic bipolar patients compared to controls and that short and long-term administration can lead to prolactin changes different from each other. 2. Twenty euthymic bipolar male patients on long-term lithium carbonate treatment for more than 6 months and 15 euthymic male bipolar patients on short-term Li treatment for shorter than 6 months who met DSM-IV criteria for bipolar affective disorder were included in the study. Seventeen age-matched healthy control males were chosen among the hospital staff. The mean +/- SD duration of Li use was 68.93+/-46.31 months in the long-term lithium-treated group and 4+/-3.42 months in the short-term lithium-treated group. 3. Serum PRL values in the long-term Li-treated group were significantly lower than those of the control group, while there was no significant difference in PRL values between the short-term Li-treated group and the control group. 4. Our study documents that short-term (<6 months) Li treatment does not induce any significant changes in PRL release in bipolar patients compared to normal control subjects while long-term Li treatment (>6 months) leads to lower PRL release compared to the controls. Furthermore, PRL has wide intra-interindividual and circadian variations Li-PRL relationship seems to be very complex and probably depends on various interactions among dopamine, serotonin and PRL. Therefore, further studies are needed to confirm the data.     

Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.     

双相情感障碍抑郁发作急性期治疗后残留症状及其 影响因素

目的 探索双相障碍抑郁发作急性期治疗后的残留症状、功能损害及其影响因素。 方法 本研究为单中心、横断面研究，筛查2016 年2—12 月就诊于首都医科大学附属北京安定医院门 诊或住院的双相障碍且最近一次是抑郁发作的患者130 例。通过标准化的问卷及访谈过程收集人口学 资料、疾病临床特征。结果 共纳入121 例受试者，其中有残留抑郁症状患者23.1%（28/121）。临床痊 愈与残留抑郁症状两组在性别（χ2=17.90，P＜ 0.01）、急性期伴有睡眠障碍（χ2=7.37，P=0.01）、近2 年的 发作次数（Z=-2.46，P=0.01）等方面差异有统计学意义，二分类Logistic 回归显示男性、急性期伴有睡眠 障碍、近2 年发作次数多，均是急性期治疗后残留抑郁症状的独立危险因素。残留抑郁症状组各方面受 损程度较临床痊愈组严重，且与抑郁程度呈正相关。结论 双相障碍抑郁发作急性期治疗后部分患者 仍然存在残留的抑郁症状，其中男性、急性期伴有睡眠障碍、近2 年发作次数多是其危险因素，残留的 抑郁症状对患者影响严重，应该加强针对性治疗，以改善预后。     

Brain GABA levels in patients with bipolar disorder

Purpose

A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients.

General methods

We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls.

Findings

There were no significant differences in GABA, glutamate or glutamine between patients and controls.

Conclusions

Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder.     

双相障碍患者治疗前后甲状腺激素水平的变化

目的了解血清甲状腺激素水平与双相障碍患者治疗前后的关系。方法对63例门诊及住院双相障碍患者双相躁狂34例,双相抑郁29例,治疗前后血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)和促甲状腺激素(TSH)进行检测,同时以30名健康志愿者作为对照组。治疗前后应用汉密尔顿抑郁量表(HAMD)、Montgomery-Asbery抑郁量表(MADRS)、Young躁狂量表(YMRS)、Bech-Rafaelsen(BRMS)躁狂量表和躁狂抑郁印象量表(CGI-BP)评定抑郁和躁狂症状的严重程度。结果患者治疗前后的T3[(2.07±0.53)和(2.14±0.78)nmol/L]明显高于对照组[(1.58±0.27)nmol/L,P<0.01]。双相躁狂治疗前后T4[(99.33±24.45)和(86.60±20.96)nmol/L]比较有显著性差异(P<0.01)。双相抑郁治疗前后T4[(101.78±28.07)和(91.96±35.46)nmol/L]比较无显著性差异(P>0.05)。HAMD、MADRS、YMRS和BRMS评分也随之明显下降。结论提示双相障碍患者治疗前后甲状腺激素改变与症状的消失有关,甲状腺激素异常是继发于情绪障碍,双相障碍在病因学方面可能不同。     

Ziprasidone: efficacy and safety in patients with bipolar disorder

Atypical antipsychotics have been increasingly shown to have efficacy in the treatment of various phases of bipolar disorder. Ziprasidone acts primarily through serotonergic and dopaminergic receptor antagonism, and exerts effects as an inhibitor of serotonin and norepinephrine reuptake. Ziprasidone exhibits dose proportional, linear changes in exposure and is hepatically metabolized primarily by aldehyde oxidase. In studies of patients with acute manic or mixed episodes, treatment with ziprasidone monotherapy or in combination with lithium, resulted in rapid symptom improvement and was generally well tolerated. Results from open-label extension studies of ziprasidone indicate continued improvement in manic symptoms. Preliminary data in pediatric patients with bipolar disorder also suggest it may be efficacious in this population. Ziprasidone is considered as a first-line treatment option in patients with bipolar manic or mixed episodes, with or without psychosis and displays a favorable side-effect profile.     

双相障碍I型患者治疗前后微小RNA206基因表达水平变化及与对照的比较

背景微小RNA206（MicroRNA-206,miRNA-206）可能是双相障碍的生物学标志之一,有待深入探究。目的评估双相障碍躁狂发作期外周血miRNA-206水平与患者临床状态的关系。方法采用美国精神障碍诊断与统计手册第4版轴I障碍定式临床检查,符合双相障碍I型躁狂发作期的新入院患者36例和年龄、性别匹配的健康对照者30名纳入研究。健康对照者入组时,双相障碍患者在基线、治疗后第2,4、8周末外周血淋巴细胞miRNA-206水平被检测。在检测miRNA-206水平相同时间点,采用杨氏躁狂量表（YoungManiaRatingScale,YMRS）评估双相障碍患者躁狂症状严重程度。结果在基线（Z=-0．02,P=0．988）和治疗后第2周末（Z=-0．17,P=O．864）、第4周末（Z=-0．86,P=O．392）、第8周末（Z=-1．29,P=0．197）,双相障碍患者与健康对照者之间外周血miRNA-206水平差异无统计学意义。对于双相障碍患者,在4个时间点miRNA-206水平与躁狂症状严重程度之间也无统计学明显相关（统计值依次为：rs=0．13,P=0．518;rs=0．12,P=0．532;rs=-0．18,P=0．361：rs=0．02,P=0．912）。结论外周血淋巴细胞miRNA-206水平可能不是双相障碍I型或躁狂发作期治疗效果的生物学标志。由于本研究检测患者与对照者之间差异的统计效能仅22％,今后需要大样本研究（可能应用不同技术检测miRNA-206水平）进一步验证。     

MicroRNA-134 plasma levels before and after treatment for bipolar mania

Studies have previously documented that microRNAs (miRNAs), with their key roles in regulating both synaptic plasticity and brain development, are candidate genetic contributors to the etiopathology of bipolar disorder (BD). Moreover, miRNA identified as targets for the actions of chronic lithium and VPA are known to play diverse and intriguing roles in brain function. In particular, the brain specific miR-134 has recently been identified as a potential regulator of dendritic spine volume and synapse formation. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. We assessed the hypothesis that miRNA-134 may be present and detectable in circulating blood, and that miRNA-134 may serve as a biomarker of mania episodes in BD. In the present study, we recruited 21 bipolar I, manic (DSM-IV) patients and controls matched by sex and age for quantification of miR-134 level in plasma using real-time RT-PCR method. We found that: Plasma miR-134 levels in drug-free, 2-week medicated, and 4-week medicated bipolar mania patients were significantly decreased when compared with controls, and the level was increased on following medication. Decreased circulating miR-134 level both in drug-free and medicated patients did presented negative correlation with the clinical scales. Overall, these results suggest that the decreased plasma miR-134 levels may be directly associated with the pathophysiology and severity of manic symptoms in BD. Plasma miRNA-134 in BD may be considered as a potential peripheral marker that can respond to acute manic episodes and associate with effective mood stabilizers treatment.