焦虑症的生化病理机制探讨

目的：从神经递质与神经内分泌角度探讨焦虑症的生化病理机制。方法：采用高效液相色谱法及放射免疫测定法，分别测定25例焦虑症患者和28例正常对照者血小板5—羟色胺(5—HT)含量及血浆催乳素(PRL)含量、地塞米松抑制实验(DST)皮质醇含量。结果：广泛性焦虑(GAD)组血小板5—HT水平高于正常对照组，惊恐障碍(PD)组与正常对照组无显著差异；GAD组与对照组血浆PRL均极显著低于PD组；GAD组与PD组血浆基础皮质醇含量均显著高于正常对照组，两组DST阳性率均为20％，正常对照组为14．3％，3组阳性率无显著性差异；汉密尔顿焦虑量表(HAMA)评分与血浆皮质醇浓度呈显著正相关。结论：焦虑症患者存在神经递质和神经内分泌功能的紊乱，但不同亚型间可能存在不同的病理机制，皮质醇浓度可能是焦虑水平的标志因子。     

无先兆偏头痛患者血浆及血小板5-HT、5-HIAA含量的变化

目的　了解 5 -羟色胺 (5 - HT)、5 -羟吲哚乙酸 (5 - HIAA)在无先兆偏头痛发病中的作用。方法　用荧光分光光度法检测 2 0例无先兆偏头痛患者 (病例组 )和 2 3名正常人 (对照组 )血浆及血小板 5 - HT、5 - HI-AA的含量。结果　病例组发作期血浆 5 - HT含量低于对照组 (P<0 .0 5 ) ,而 5 - HIAA高于对照组 (P<0 .0 5 ) ;间歇期血浆 5 - HT高于发作期 (P<0 .0 5 ) ,而 5 - HIAA含量低于发作期 (P<0 .0 5 )。发作期血小板 5 - HT含量显著高于间歇期和对照组 (P<0 .0 1) ,而 5 - HIAA含量显著低于间歇期和对照组 (P<0 .0 1)。病例组 (含发作期和间歇期 )血小板 5 - HT含量高于对照组 (P<0 .0 5 ) ,而 5 - HIAA含量显著低于对照组 (P<0 .0 5 )。结论　无先兆偏头痛患者不同时期其血浆和血小板 5 - HT、5 - HIAA含量发生不同变化     

抑郁症患者单胺类神经递质与血脂的相关性

目的：探讨抑郁症患者血浆单胺类神经递质与血脂的关系。方法：检测55例抑郁症患者和21例正常人的血浆去甲肾上腺素(NE)、5—羟色胺(5—HT)、血清总胆固醉(CH0)、甘油三酯(TG)、高密度脂蛋白—胆固醇(HDL-C)和低密度脂蛋白—胆固醇(LDL-C)。结果：抑郁症患者的血浆5—HT浓度和血清CH0浓度显著低于正常对照组，血浆NE浓度显著高于正常对照组；抑郁症患者的血浆5-HT浓度和血清CH0浓度呈显著正相关，血浆NE浓度与血清HDL-C浓度呈显著正相关。结论：抑郁症患者的血脂代谢异常与血浆单胺类神经递质有关。     

儿童孤独症血浆5-羟色胺的测定

目的 比较孤独症儿童和正常儿童血浆5-羟色胺(5-HT)的浓度,探索5-HT浓度增高和5-HT浓度正常的孤独症儿童各自的临床特点。方法 采用孤独症行为评定量表(ABC)、儿童期孤独症评定量表(CARS)和适应行为评定量表对33例孤独症儿童进行评定,并进行了血浆5-HT检测,以高出正常儿童平均5-HT浓度1.67个标准差的孤独症儿童为5-HT增高组,其他孤独症儿童为5-HT正常组,比较两组孤独症儿童的临床特征。结果 孤独症儿童的ABC得分为72.30±29.91、CARS的得分为41.83±4.05、适应行为评定量表的得分为66.55±12.52。孤独症儿童5-HT浓度为0.77±0.33μmol/L;正常儿童5-HT浓度为0.62±0.18μmol/L,两组经t检验有显著性差异(t=2.23;P=0.03)。5-HT增高的孤独症儿童有9例,5-HT正常的孤独症儿童有24例,两组临床特征比较未发现明显差异。结论 27.3％的孤独症儿童5-HI浓度增高,5-HT增高与5-HT正常的儿童孤独症临床特征相同。孤独症的病因可能是异质性的。     

儿童孤独症的血浆谷氨酸和γ-氨基丁酸水平及其与伴发癫痫的关系

目的 探讨血浆谷氨酸(Glu)和γ-氨基丁酸(GABA)水平异常与儿童孤独症的关系,及其在儿童孤独症易发癫痫病理机制中的作用.方法 从已经收集血样的儿童孤独症患者库(278例)中随机选择34例为总的患者组,其中不伴癫痫者30例(不伴癫痫组),伴癫痫者4例;而此库中所有伴发癫痫的27例患者为伴癫痫组,正常儿童36名为对照组.采用高效液相色谱法测定血浆Glu和GABA水平并进行上述3组间的比较.结果 孤独症患者伴发癫痫的比例为9.7%(27/278).总患者组的血浆Glu和GABA水平与对照组的差异均无统计学意义(t=1.09,P:0.28;t=0.56,P=0.58).两两比较:伴癫痫组血浆Glu水平显著高于不伴癫痫组和对照组(H=8.93,P=0.003;H=10.65,P=0.001),而后两组间的差异无统计学意义(H=0.00,P=1.00);此3组间血浆GABA水平差异无统计学意义(H=5.38,P=0.07,df=2).Pearson相关分析显示,患者组的血浆Glu及GABA水平分别与性别、年龄、病程、孤独症行为评定量表(Autism Behavior Checklist,ABC)评分等的相关均无统计学意义(P＞0.05).结论 仅在伴发癫痫的孤独症儿童中发现血浆Glu水平的异常增高,这可能是孤独症易发癫痫的病理机制之一.     

血清抗神经节苷脂M1抗体水平与儿童孤独症严重程度的相关性研究

目的 了解血清抗神经节苷脂M1(GM1)抗体水平的变化及其与儿童孤独症严重程度的关系,为儿童孤独症的病因及治疗提供线索和依据. 方法 病例组选择自2012年6月至8月在广州市小天使康复训练中心进行康复训练的已确诊的孤独症患儿50例,对照组选择同期在广东省妇幼保健院儿童保健科门诊体检正常的儿童50例.采用酶联免疫吸附法(ELISA)检测2组儿童血清抗GM1抗体水平.根据儿童孤独症评定量表(CARS)评定孤独症患儿的疾病严重程度.比较组间及不同疾病严重程度、性别间抗GM1抗体水平并行相关性分析. 结果 根据所测得的抗GM1抗体截断值(156.18 ng/mL)判断,24％(12/50)的孤独症患儿抗GM1抗体阳性,对照组仅4％(2/50)抗GM1抗体阳性,差异有统计学意义(P＜0.05).7.7％(2/26)轻中度孤独症患儿抗GM1抗体阳性,而41.7％(10/24)重度孤独症患儿抗GM1抗体阳性,差异有统计学意义(P＜0.05).孤独症组抗GM1抗体水平[12.79(146.02) ng/mL]高于对照组[11.35(53.80) ng/mL],差异有统计学意义(P＜0.05).女性孤独症患儿抗GM1抗体水平[191.74(216.18) ng/mL]高于男性患儿[11.11(9.51) ng/mL],差异有统计学意义(P＜0.05).相关性分析显示,孤独症患儿血清抗GM1抗体水平与CARS评分呈正相关(r=0.866,P＜0.005). 结论 血清抗神经节苷脂GM1抗体水平可能是孤独症的一项生化标志,与儿童孤独症的严重程度相关.     

焦虑和抑郁障碍共病血浆单胺类神经递质研究

目的：探讨血浆单胺类神经递质与焦虑和抑郁障碍共病的关系。方法：使用高效液相－电化学检测法检测25例焦虑和抑郁障碍共病、30例抑郁症、20例焦虑症患者和21例正常人的血浆去甲肾上腺素（NE）和5－羟色胺（5－HT）浓度。结果：3组患者的血浆NE浓度均显著高于正常对照组,但共病组与抑郁症组和焦虑症组无明显差异;抑郁症组的血浆5－HT浓度显著低于正常对照组,共病组和焦虑症组的血浆5－HT浓度与正常对照组无显著差异,3组患者之间血浆5－HT浓度也无显著差异。结论：血浆单胺类神经递质不能鉴别抑郁症和焦虑症,也不支持焦虑和抑郁障碍共病是第3种疾病的观点。     

血微量元素与儿童孤独症及症状严重程度的相关性

目的:探讨儿童孤独症患者全血微量元素含量,以及与儿童孤独症症状严重程度的相关性。方法:选取25例儿童孤独症患者作为病例组,30例健康者作为对照组,采用原子吸收分光光度法对被试的全血铜、锌、钙、镁和铁离子水平进行测定;采用儿童孤独症行为量表(AutismBehaviorChecklist,ABC)对病例组的症状进行评估。结果:与对照组相比,病例组的血镁和锌离子含量降低(t=-12.435,P<0.001;t=-11.44,P<0.001),而血铜离子含量增高(t=3.915,P<0.05),差异具有统计学意义。两组的其余血微量元素含量差异不显著。儿童孤独症行为量表的得分与血镁、锌离子含量呈显著负相关(r=-0.813,P<0.001;r=-0.785,P<0.001),与血铜离子含量呈显著正相关(r=0.466,P<0.001)。结论:孤独症患儿症状的严重水平与血镁和锌离子含量降低,血铜离子含量增高有密切关系,血微量元素含量异常可能是诊断儿童孤独症的敏感生物学指标之一。     

五羟色胺与孤独症

本文介绍了 5 羟色胺 (5 HT)在孤独症患者中的生物化学和分子生物学特性 ,探讨了 5 HT与孤独性障碍的关系 ,对 5 HT系统功能水平、 5 HT受体基因的不同表达等可能与孤独症的关系作一综述     

儿童孤独症与感觉统合失调的相关分析

目的:探索儿童孤独症与感觉统合失调的关系.方法:对60例符合国际疾病分类第10版(ICD-10)诊断标准的儿童孤独症患儿(患者组)与60名健康儿童(对照组)填写儿童情况调查表,并分别进行感觉统合评定量表(SIS)、克氏孤独症行为量表(CBRS)及并儿童孤独症评定量表(CARS)评定孤独症患儿症状严重程度.结果:患者组伴感觉统合失调的占95.0%,而对照组存在感觉统合失调的仅占3.3%;患者组与对照组的感觉统合评定结果比较,差异具有显著性(P＜0.01);病程长短不同的患儿感觉统合失调严重度不同,差异具有显著性(P＜0.05);智力水平与感觉统合失调显著相关(P＜0.05);多元逐步回归分析结果:是否诊断为儿童孤独症与CBRS总分、本体感、母孕期有无高危因素、既往有重大疾病史、有无窒息史、母亲文化程度有关.结论:儿童孤独症患儿普遍存在感觉统合失调,在对儿童孤独症患儿进行个别化训练的同时应进行感觉统合训练.     

Low platelet-poor plasma levels of serotonin in adult autistic patients

BACKGROUND: Hyperserotonemia has been reported in about a third of autistic patients. However, most studies have examined whole blood levels of serotonin (5-HT), the vast majority of which is found in platelets. The aim of this study was to determine 5-HT levels in platelet-poor plasma (PPP) in a group of adult patients with autism. METHODS: Levels of PPP 5-HT were compared between 10 adult drug-free autistic patients and 12 healthy controls. The Ritvo-Freeman Real-Life Rating Scale and the Overt Aggression Scale (OAS) were administered to the autistic group as a measure of symptom severity. RESULTS: Significantly lower PPP 5-HT levels were observed in the autistic group as compared to the controls (p = 0.03). In addition, PPP 5-HT levels were inversely correlated with OAS scores among subjects with autism (r = -0.64, p < 0.05). CONCLUSION: PPP 5-HT ('free') levels appear to be low in autistic patients and may play a role in the pathophysiology and symptomatology of the disorder.     

Increased growth hormone response to sumatriptan challenge in adult autistic disorders

Serotonergic (5-HT) abnormalities have been documented in autism. To assess sensitivity of the 5-HT1d receptor, growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls. In this study, 11 adult patients with autism or Asperger's disorder were compared with nine matched controls. All subjects were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a 1-week interval, and growth hormone was measured before and during the challenges. The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline. This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls, independent of placebo effects. Therefore, abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism.     

儿童孤独症与5-羟色胺转运体基因连锁多态性区域的关联性研究

目的:探讨汉族人群中5-羟色胺转运体基因连锁多态性区域(5-HTTLPR)与儿童孤独症(CA)的相关性. 方法:采用病例对照研究、聚合酶链反应(PCR)的方法对中国汉族CA患儿与5-HTTLPR的关联性进行研究.以健康儿童作对照. 结果:中国汉族CA患者的5-HTTLPR分布与对照组差异无显著性,但CA组5-HTTLPR纯合子基因型的频率显著高于对照组;5-HTTLPR的基因型与CA的躯体运动因子显著相关. 结论:5-HTTLPR与CA的主要症状存在显著关联;5-HTTLPR的纯合子基因型和等位基因L可能增加了CA的患病危险.     

Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia

The well-replicated platelet hyperserotonemia of autism has stimulated interest in serotonin (5-HT) in autism. We have examined the effects of the serotonin transporter gene (5-HTT, locus SLC6A4) promoter polymorphism (5-HTTLPR) on platelet 5-HT physiology in autism. Platelet 5-HT uptake rates and affinities (V(max) and K(m)), uptake site densities (B(max)) and 5-HT levels were examined in 31 French individuals with autism genotyped with respect to the 5-HTTLPR. Platelet 5-HT uptake and 5-HT levels were measured using HPLC; uptake sites were determined by radioligand binding. A 1.5-fold increased rate (V(max)) of platelet 5-HT uptake was observed in ll genotype individuals compared to those with ls and ss genotypes (Mann- Whitney U-test, P = 0.022). However, no significant relationship was observed between genotype and uptake site density (U-test, P = 0.51). Although median levels of platelet 5-HT in platelet-rich plasma were higher in the ll group, only trend level significance was observed (U-test, P= 0.069); platelet 5-HT content measured in whole blood was similar across genotypes. Uptake rates were well correlated with B(max) values (r = 0.66, P = 0.002); correlations between uptake and platelet 5-HT levels and between B(max) values and 5-HT levels were somewhat lower. While 5-HTTLPR alleles had an appreciable effect on platelet 5-HT uptake rates, effects on 5-HT levels and uptake site density were smaller or absent. Based on these preliminary data and prior studies of allele frequencies, we conclude that the 5-HTTLPR is not a major determinant of the group mean platelet serotonin elevation seen in autism. However, a role for increased uptake in the hyperserotonemia of autism can not be ruled out. In addition, it appears that studies of platelet 5-HT measures in autism and other disorders should take account of the effects of 5-HTTLPR genotype on 5-HT uptake     

Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women

Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity.     

Brief Report: Platelet-Poor Plasma Serotonin in Autism

Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the platelet to 5-HT. Mean (± SD) concentrations of PPP 5-HT observed in the autism (N = 18), hyperserotonemic subgroup (N = 5) and control (N = 24) groups were 0.86 ± 0.53, 0.87 ± 0.43 and 0.86 ± 0.36 nM, respectively. The results suggest that the hyperserotonemia of autism is not due to increased exposure of the platelet to 5-HT and make it more likely that the factor(s) contributing to the hyperserotonemia of autism have to do with the platelet's handling of 5-HT.     

孤独症核心家系5—HT和APOE基因的关联研究

目的 探讨孤独症与5-HT基因和APOE基因之间的关系。方法 应用PCR-RFLP技术对符合国际疾病分类第10版(ICD-10)中孤独症诊断标准的21例孤独症患儿和他们的父母进行了5-HT2a,5-HT6和APOE多态性的检测。结果 孤独症患儿与对照组5-HT2a,5-HT6和APOE的基因频率和基因型频率的分布呈基本一致的趋势,两组间未显示具有统计学意义的差别。采用基于单体型的单体型相对风险率分析方法,发现仅5-HT6基因中T等位基因与孤独症显著关联(RR=3.59,P<0.05)。传递不平衡检验(TDT)发现孤独症可能与5-HT6中T等位基因相连锁(McNemarX~2=5.4,P<0.05)。结论 5-HT6基因与孤独症的发病可能存在关联或连锁关系。     

Plasma cyclic AMP and cyclic GMP in childhood-onset psychoses

Plasma cyclic AMP is a “second messenger” that may reflect levels of activity of important neurotransmitter receptors. Plasma cyclic AMP was measured in 18 patients with childhood autism, 7 patients with pervasive developmental disorder, and 12 age- and sex-matched healthy controls. Plasma cyclic AMP was significantly elevated by over 100% in both groups of patients with childhood-onset psychoses compared with controls. Plasma cyclic GMP, a nucleotide linked to different receptors, was not elevated, suggesting that the finding may be specific.     

Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates

OBJECTIVE: To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). METHOD: Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined. RESULTS: Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels. CONCLUSIONS: The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.     

Urinary 5-hydroxyindoleacetic acid and whole blood serotonin and tryptophan in autistic and normal subjects

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in two consecutive collection periods (5:00 PM-11:00 PM and 11:00 PM-8:00 AM) and whole blood serotonin (5-HT) and tryptophan (TRP) were measured in groups of unmedicated autistics (n = 16), medicated autistics (n = 20), and normal controls (n = 27). Whole blood 5-HT values were significantly higher in unmedicated autistics compared to normal controls. No significant differences were found in 5-HIAA excretion (microgram/mg creatinine, mean +/- SD) between unmedicated autistics (4.07 +/- 1.52) and normal controls (3.50 +/- 1.07), or between medicated (5.35 +/- 2.93) and drug-free autistic individuals. No correlations were found between 5-HT values and urinary 5-HIAA excretion. Urinary 5-HIAA (microgram/mg creatinine, mean +/- SD) was significantly greater in hyperserotonemic autistic subjects (4.88 +/- 0.87) compared to normal controls (3.50 +/- 1.07, total collection period; p = 0.002). The relevance of these findings to the possibility that increased gut production of 5-HT might cause the elevated whole blood 5-HT levels seen in autism is discussed.