广泛性焦虑症首次发病患者治疗前后前额叶皮质及海马神经生化物质的变化

目的:观察广泛性焦虑症(GAD)首次发病患者坦度螺酮治疗前后双侧前额叶皮质及海马神经生化物质的变化。方法:对39例首发的GAD患者(GAD组)给予坦度螺酮治疗8周;分别于治疗前后进行汉密尔顿焦虑量表(HAMA)评分及磁共振质子波谱分析(1H-MRS)检测双侧前额叶及海马N-乙酰天门冬氨酸(NAA)、谷氨酸复合物(Glx)、胆碱复合物(Cho)、肌酸(Cr)水平;并与30名正常对照者(正常对照组)比较。结果:治疗前GAD组右侧额叶NAA/Cr、Cho/Cr值显著低于正常对照组(P0.05或P0.01),Glx/Cr值明显高于正常对照组(P0.01);治疗后右侧额叶NAA/Cr、Cho/Cr值显著高于正常对照组(P0.05或P0.01);治疗前后左侧额叶及双侧海马各代谢指标相对浓度与正常对照组差异无统计学意义。相关分析显示,GAD组HAMA总分与右侧额叶NAA/Cr呈负相关(r=-0.732),与Glx/Cr呈正相关(r=0.569)(P均0.01)。结论:GAD患者发病初期即存在右侧前额叶神经元代谢异常;坦度螺酮抗焦虑疗效可能与其调整脑组织代谢有关。     

精神分裂症患者脑部质子波谱特点及其与临床症状的关系

目的 探讨精神分裂症患者前额叶、丘脑氧质子磁共振波谱(proton magnetic resonance spectroscopy,1H-MRS)的特点及其与临床症状的关系.方法 本研究纳入7 d内未使用抗精神病药物及影响脑内乙酰胆碱神经递质药物的32例精神分裂症患者和36名正常对照,入组24 h内采用多体素1H-MRS检测受试者前额叶和丘脑生化代谢物N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),并计算NAA/Cr、Cho/Cr和NAA/(Cho+Cr)的比值.患者组同时进行阳性和阴性症状量表(PANSS)评估.结果 患者组左侧前额叶及左右侧丘脑NAA/Cr值[分别为(1.30±0.39)、(1.53±0.36)和(1.47±0.35)]均低于对照组[分别为(1.74±0.24)、(1.73±0.25)和(1.74±0.31)],差异具有统计学意义(P＜0.05);患者组左侧前额叶NAA/(Cho+cr)值[(0.63±0.12)]低于对照组[(0.74±0.21)],差异具有统计学意义(P＜0.05).患者组左侧前额叶NAA/Cr值与PANSS总分及阴性症状分呈负相关(r=-0.48,P＜0.01;r=-0.54,P＜0.01),右侧丘脑NAA/Cr值与阴性症状呈负相关(r=-0.44,P＜0.01).结论 精神分裂症患者前额叶及丘脑存在神经元功能和(或)结构异常,左侧前额叶NAA/Cr值可能作为反映精神分裂症患者阴性症状严重程度的参考指标.     

不同性别首发精神分裂症患者前额叶和丘脑质子波谱的比较研究

目的探讨首发精神分裂症患者前额叶和丘脑神经生化代谢物质的特点及其性别差异。方法纳入首发精神分裂症患者男性33例、女性31例以及男性正常对照30名、女性正常对照22名,采用多体素磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)检测前额叶和丘脑N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),完成NAA/Cr值、Cho/Cr值的计算。患者在抗精神病药物治疗8周末复查1H-MRS,治疗前后采用阳性与阴性症状量表(positive and negative syndrome scale,PANSS)评定临床症状和疗效。结果治疗前,男性患者组、女性患者组左侧前额叶NAA/Cr值[(1.38±0.33)、(1.37±0.35)]、左侧丘脑NAA/Cr值[(1.47±0.35)、(1.45±0.38)]均分别低于同性别正常对照组[(1.61±0.38)、(1.63±0.37)和(1.71±0.38)、(1.72±0.39)],差异均有统计学意义(P0.05)。治疗前与治疗后,男性与女性患者组之间1H-MRS各代谢指标的差异均无统计学意义(P0.05),两组中NAA/Cr值、Cho/Cr值的治疗前后自身比较均无明显差异(P0.05)。男性患者组治疗前后左侧前额叶NAA/Cr变化值分别与PANSS总分及阴性症状因子分的变化值呈负相关(r=-0.39,P0.05;r=-0.43,P0.05)。结论未发现首发精神分裂症患者前额叶和丘脑代谢物存在明显的性别差异,但男性左侧前额叶NAA浓度的变化与阴性症状的变化可能有关。     

双相抑郁患者前额叶和前扣带回皮质氢质子波谱研究

目的:研究双相抑郁患者前额叶皮质、前扣带回皮质代谢物的相对含量。方法:对30例未服药双相抑郁患者和30名健康志愿者的前额叶皮质、前扣带回皮质进行氢质子波谱(1H-MRS)扫描,双相抑郁患者经6周药物治疗后再次做1H-MRS扫描,检测N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、谷氨酸复合物(Glx)、肌酸(Cr)4种代谢物。结果:双相抑郁组左侧前额叶皮质、双侧前扣带回皮质NAA/Cr值均显著低于正常对照组(P<0.05),Cho/Cr值、Glx/Cr值均显著高于正常对照组(P<0.05),双相抑郁组右侧前额叶皮质NAA/Cr、Cho/Cr、Glx/Cr值两组比较差异无统计学意义(P>0.05)。经药物治疗后,左侧前额叶皮质、双侧前扣带回皮质NAA/Cr值较治疗前升高,Cho/Cr值、Glx/Cr值较治疗前降低,差异有统计学意义(P<0.05)。结论:前额叶和前扣带回皮质NAA、Cho、Glx含量的改变与双相抑郁的发生和药物的疗效有关。     

首发未治精神分裂症神经系统软体征与脑内神经生化代谢物的相关性研究

目的探讨首发未经治疗的精神分裂症患者用药前脑内神经生化代谢物质的特点及其与神经系统软体征之间的相关性。方法研究组纳入符合《中国精神障碍分类与诊断标准第3版》(CCMD-3)诊断标准的首发未治精神分裂症患者33人(男19人、女14人)。对照组为健康成人33人(男14人、女19人)。选取部分额、颞叶功能测试量表评定其神经系统软体征。采用单体素氢质子磁共振波谱(1H-MRS)检测左侧前额叶和丘脑N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)、肌酸复合物(Cr)与磷酸化肌酸复合物(Cr2)的水平,并计算NAA/Cr值、Cho/Cr值、Cr2/Cr值、NAA/Cho值。结果研究组左侧前额叶Cr2/Cr值(1.15±0.87)显著高于对照组Cr2/Cr值(0.72±0.46)(P0.05)。NSS量表总分研究组(10.33±5.07)显著高于对照组(4.18±2.15)(P0.05)。研究组NSS总分与左侧前额叶Cr2/Cr值呈正相关(P0.05),与左侧前额叶NAA/Cho值呈负相关(P0.05)。结论首发未治精神分裂症神经系统软体征明显,提示可能存在中枢神经系统的整合缺陷,其脑内部分神经生化代谢物与神经系统软体征存在相关性。     

初发抑郁症患者丘脑质子磁共振波谱分析

目的探讨未用药首发抑郁症患者丘脑的脑代谢有无异常。方法利用质子磁共振波谱分析技术(1H-MRS)检测20例未用药首发抑郁症患者和20名健康志愿者丘脑的多个代谢指标,包括乙酰天门冬氨酸盐(NAA)、谷氨酰胺和谷氨酸复合物(Glx)、胆碱复合物(Cho)、肌酸-磷酸肌酸复合物(Cr)等。结果与对照组相比,患者组双侧丘脑NAA/Cr下降,但只有右侧的差异有统计学意义(t=2.923,P<0.05);两组间各代谢值、Cho/Cr和Glx/Cr的差异无统计学意义(P>0.05);轻度抑郁组和重度抑郁组间比较,各代谢值的差异均无统计学意义(P>0.05)。结论初发抑郁症患者右侧丘脑可能存在神经元受损和线粒体代谢障碍。     

男性精神分裂症患者前额叶质子波谱特点及其与执行功能的关系

目的探讨男性精神分裂症患者前额叶氢质子磁共振波谱(proton magnetic resonance spectrosco-py,1H-MRS)的特点及与执行功能的关系。方法纳入26例7d内未使用抗精神病药物及影响脑内乙酰胆碱神经递质药物的男性精神分裂症患者及28名男性正常对照。两组在入组24h内采用多体素1H-MRS检测前额叶生化代谢物N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),完成NAA/Cr值、Cho/Cr值和NAA/(Cho+Cr)值的计算,同时进行威斯康星卡片分类测验(Wisconsin Card Sorting Test,WCST)评定受试者的执行功能。结果患者组左侧前额叶NAA/Cr值(1.40±0.34)低于对照组(1.69±0.31),差异有统计学意义(t=2.93,P0.01)。患者组WCST的错误应答数、持续应答数、持续错误数均明显高于对照组(t分别为2.32、2.25、2.40,P均小于0.05),分类数和概念化水平应答数均明显低于对照组(t=2.91,P0.01;t=2.46,P0.05)。患者组左侧前额叶NAA/Cr值与错误应答数、持续错误数呈正相关(r=0.45,P0.05;r=0.47,P0.05),与分类数、概念化水平应答数呈负相关(r=-0.54,P0.01;r=-0.56,P0.01)。结论男性精神分裂症患者左侧前额叶可能存在神经元功能和(或)结构异常,这可能是引起额叶执行功能障碍的原因。     

高频或低频重复经颅磁刺激治疗对抑郁障碍患者局部脑内代谢物质的影响

目的:探讨高频或低频重复经颅磁刺激(rTMS)治疗对抑郁障碍患者局部脑内代谢物质的影响。方法:随机将40例抑郁障碍患者分成高频和低频r TMS组并进行相应的r TMS治疗4周。治疗前后应用汉密尔顿抑郁量表(HAMD)评定患者的病情,应用氢质子磁共振波普成像(1H-MRS)检测前额叶皮质N-22乙酰天门冬氨酸(NAA)、谷氨酸(Glx)、胆碱复合物(Cho)及肌酸(Cr)代谢物水平,并与20名正常对照者(对照组)比较。结果:两r TMS组分别有12例患者完成治疗,治疗后两组HAMD评分显著低于治疗前(P均0.01)。与对照组比较,治疗前两r TMS组左侧前额叶皮质NAA/Cr、Glx/Cr、右侧前额叶皮质NAA/Cr显著降低(P均0.01),治疗后都有明显升高(P均0.05)。结论:抑郁障碍患者双侧前额叶NAA及左侧前额叶Glx水平降低;高、低频r TMS治疗后患者双侧前额叶NAA及左侧前额叶Glx水平提高,可能是r TMS治疗抑郁障碍的机制之一。     

首发未用药精神分裂症患者脑内神经生化代谢物与认知功能的相关性

目的 探讨首发未经治疗的精神分裂症患者用药前脑内神经生化代谢物质的特点及其与 认知功能之间的相关性。方法 纳入首发未治精神分裂症患者33例（男性19例、女性14例）作为研究组, 对照组为符合纳入标准的健康成人33人（男性14名、女性19名）。采用单体素氢质子磁共振波谱（1H-MRS） 检测左侧前额叶和丘脑N-乙酰基天门冬氨酸（NAA）、胆碱复合物（Cho）、肌酸复合物（Cr）与磷酸化肌酸 复合物（Cr2）的水平,并计算NAA/Cr 值、Cho/Cr 值、Cr2/Cr 值、NAA/Cho 值。选取剑桥神经心理自动化成 套测试（CANTAB）中的图形识别记忆（PRM）延迟再识别正确率评定其认知功能。结果 研究组左侧前 额叶Cr2/Cr 值（1.15±0.87）高于对照组（0.72±0.46）,差异有统计学意义（P ＜ 0.05）。左侧前额叶NAA/Cr 值、Cho/Cr 值、NAA/Cho 值以及丘脑NAA/Cr 值、Cho/Cr 值、Cr2/Cr 值、NAA/Cho 值与对照组比较差异均 无统计学意义（P ＞ 0.05）。CANTAB 认知测试中PRM 正确率,研究组为（82.81±15.44）% 低于对照组的 （95.20±6.26）%,差异有统计学意义（P ＜ 0.05）。Pearson 相关分析发现,研究组左侧前额叶Cho/Cr 值与 PRM 正确率呈负相关（r=-0.424,P ＜ 0.05）,NAA/Cho 值与PRM 正确率呈正相关（r=0.473,P ＜ 0.01）。研 究组左侧前额叶NAA/Cr 值、Cho/Cr 值与PANSS 总分呈正相关（r=0.538、0.450,P ＜ 0.01）。结论 首发 未治精神分裂症患者用药前存在认知功能缺陷,其左侧前额叶部分神经生化代谢物质神经元细胞膜磷 酸化水平在用药前就出现了异常。提示首发未治精神分裂症患者用药前的认知功能损害与前额叶神经 生化代谢功能异常存在一定的相关性。     

抑郁症首次发病患者海马磁共振质子波谱成像的研究

目的 探讨抑郁症首次发病患者海马的磁共振质子波谱(1H-MRS)代谢物质的变化.方法 对99例首次发病的抑郁症患者和26例健康对照组行磁共振常规扫描及1H-MRS检查,测量双侧海马N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)和肌酸(Cr)三种代谢物质,计算NAA/Cr和Cho/Cr比值.结果 抑郁症患者海马NAA/Cr左右侧比值(1.23±0.16;1.16±0.16)低于对照组NAA/Cr左右侧比值(1.38±0.23;1.31±0.26),差异有显著性(P<0.05);抑郁症患者海马体部Cho/Cr左右侧比值(1.19±0.14;1.18±0.12)高于对照组Cho/Cr左右侧比值(1.14±0.12;1.11±0.14),差异有显著性(P<0.05).对照组左右侧NAA/Cr和Cho/Cr比较差异无显著性(P>0.05).抑郁症组右侧NAA/Cr低于左侧,差异显著(P<0.05);左侧Cho/Cr高于右侧,差异不明显(P>0.05).结论 抑郁症患者可能存在双侧海马神经细胞代谢功能障碍,右侧神经细胞功能障碍较左侧明显.     

Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases

Summary Tetrahydroisoquinoline (TIQ) alkaloids and 1-carboxy TIQ derivatives have been found in human fluids and/or tissues. The possible biosynthetic pathways of salsolinol (Sal), taken as an example of TIQs, are discussed, and the possibility that biosynthesis occurs through a stereospecific enzymatic reaction is considered. In this respect, it is reported that the R enantiomer of Sal predominates in urines of healthy volunteers, whereas the S enantiomer predominates in port wine and possibly in other beverages and foods, suggesting that Sal present in humans could have, at least partially, and endogenous enzymatic origin.TIQs and other dopamine-derived alkaloids are weak MAO inhibitors, the R enantiomer of Sal and salsolidine being more potent than the S form.The changes in monoamine oxidase activity and the nigrostriatal concentrations of dopamine and homovanillic acid in Parkinson's and Huntington's diseases and in alcoholism are reviewed. In these pathological situations, changes in the levels of dopamine-derived alkaloid levels may occur. The possibility that the modifications found might cause or contribute to changes in mental and/or neurophysiological states in these pathological situations is considered.     

Genetic findings in obsessive-compulsive disorder in childhood and adolescence and in adulthood

Obsessive-compulsive disorders (OCD) are on the rise, and affected children, 1-2% of the general population, often are seriously impaired in their development. OCD is characterized by recurrent, intrusive and disturbing thoughts as well as by repetitive stereotypic behaviours. Depending on their age and developmental status, patients usually try unsuccessfully to suppress the obsessive thoughts and compulsive behaviours. The current state of genetic research on OCD and early-onset OCD is presented and discussed. OCD, especially early-onset OCD, has been shown to be familial. Convincing evidence indicates that both environmental and genetic factors substantially influence OCD. Various approaches, including linkage and association studies, yielded conflicting results as well as the notion that multiple genes of modest effect sizes, in interaction with environmental factors, cause vulnerability to the disorder. The phenotypic and genetic heterogeneity of OCD complicate the identification of specific genetic factors. Further studies have to be designed in consideration of subtypes, e.g. age at onset, symptom dimensions, or comorbid disorders.     

Carbamazepine and Its Metabolites in Human Perfused Placenta and in Maternal and Cord Blood

Summary: Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatographyhass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10, 11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.     

Perceiving and acting in depth in Williams syndrome and typical development

Individuals with the neurodevelopmental disorder Williams syndrome (WS) often report difficulty processing and acting in depth, such as crossing roads or reaching for objects; however little research attention has been directed at understanding depth perception and action in depth in WS and whether deficits in depth perception have an ocular or perceptual root in this group. This study assessed the extent and relationship of deficits in stereopsis (binocular, three dimensional vision) and actions performed in depth in WS, as well as in typically developing participants (TD) matched for non-verbal ability. Stereoacuity was age-appropriate in the TD group but at the level of a TD three year old in WS; one third of the WS group did not show evidence of stereopsis. When monocularly acting in depth there was no difference between the WS and TD groups. When binocularly acting in depth the WS group that did not exhibit stereopsis were significantly poorer than the TD group and the WS group that exhibited stereopsis. When assessing the relationship between stereoacuity and action in depth, stereoacuity negatively correlated with binocular action in depth for the WS group with stereopsis, but not the TD group. Therefore, no deficits in monocular depth perception in WS were evidenced, yet significant deficits are exhibited in binocular depth perception and action. Importantly action in depth under binocular viewing may be a useful gross screening measure for stereodeficits in WS. Remediation of depth perception deficits in WS could train further understanding of monocular cues to compensate for poor stereopsis.     

Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls

Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.