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。     

坦度螺酮对焦虑症患者治疗前后额叶神经生化物质的影响分析

目的探讨坦度螺酮对焦虑症患者治疗前后额叶神经生化物质的影响。方法选择我院2014年1月至12月接诊的90例焦虑症进行研究,按随机数表法,将其分为观察组和对照组各45例。对观察组患者采用坦度螺酮治疗四周,对照组则采用丁螺环酮进行治疗。采用HAMA焦虑量表及SAS焦虑自评表对患者治疗前后进行评定分析,且采用磁共振质子波谱对患者的额叶皮质各项水平(NAA、Cho及Glx值)进行评定分析,在治疗后对两组患者的疗效进行分析,同时选择本院体检的45例正常患者进行对比。结果两组患者在治疗前的HAMA及SAS评分均无显著差异(P0.05),在治疗后,两组患者的HAMA及SAS评分均优于治疗前的评分,且观察组患者的评分明显优于对照组患者(P0.05);治疗后观察组患者的NAA、Cho及Glx值均优于对照组(P0.05);经治疗,观察组患者的总有效率为91.11%,和对照组(80%)相比,具有显著差异(P0.05)。结论焦虑症患者在发病期额叶神经元功能异常,坦度螺酮具有良好的疗效,患者的依赖性降低,有效地进行焦虑缓解和情绪调节。     

氟西汀干预对大鼠抑郁模型海马代谢的影响

目的探讨氟西汀干预对大鼠抑郁模型的海马代谢的影响。方法 45只SD大鼠随机分为正常对照组(n=15)以及抑郁组(n=30)。抑郁组又被分为干预亚组(n=15)及未干预亚组(n=15)。采用慢性不可预知应激及孤养的方法建立抑郁模型。在制模成功后不干预亚组大鼠腹腔注射生理盐水2.0 ml/d,干预亚组大鼠腹腔注射盐酸氟西汀溶液5.0 mg/(kg·d);均持续4周。于干预前后对各组大鼠进行氢质子磁共振波谱分析检查,并进行比较。结果抑郁组大鼠双侧海马N-乙酰天冬氨酸(NAA)/肌酸(Cr)及谷氨酸复合物(Glx)/Cr显著低于正常对照组,胆碱复合物(Cho)/Cr及肌醇(mI)/Cr显著高于正常对照组(P0.05~0.01)。干预亚组双侧海马的NAA/Cr及Glx/Cr显著高于未干预亚组双侧海马的Cho,ho/Cr及右侧海马的mI/Cr显著低于未干预亚组(P0.05~0.01)。与干预前比较,干预亚组干预后双侧海马NAA/Cr及Glx/Cr显著升高(均P0.05);未干预亚组双侧海马Cho/Cr及mI/Cr显著升高,NAA/Cr及Glx/Cr显著降低(均P0.05)。结论氟西汀能够改善海马神经细胞的谷氨酸循环及肌醇磷酸循环,恢复神经元及神经胶质细胞的功能。     

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。     

双相抑郁患者前额叶及海马磁共振质子波谱成像研究

目的探讨双相抑郁患者前额叶及海马磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)的代谢物变化特点,为其神经生物学研究提供线索。方法应用磁共振质子波谱成像技术检测26例双相抑郁患者(患者组)和26例单相抑郁患者及13例健康志愿者(对照组)双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(N-Acetylaspartate,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)3种代谢物,以Cr为参照物,分别计算双侧NAA/Cr和Cho/Cr比值。采用SPSS 13.0进行统计处理。结果患者组左侧前额叶白质NAA/Cr(1.65±0.31)低于对照组(2.37±0.36),左侧前额叶白质Cho/Cr(1.35±0.27)低于对照组(1.65±0.21),差异有统计学意义(P<0.05);右侧前额叶白质NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧前扣带回NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧海马NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组与单相抑郁组的双侧额叶白质、双侧前扣带回皮质、双侧海马NAA/Cr、Cho/Cr值差异均无统计学意义。结论双相抑郁患者可能存在左侧前额叶神经元功能下降和膜磷脂代谢异常,其代谢物特点存在偏侧化。     

针药治疗抑郁症过程中患者海马、额叶代谢的变化

目的：对正常志愿者、抑郁症患者脑海马、前额叶进行1H-MRS分析,探讨治疗前后脑内代谢物质的变化特点。方法：将75例轻、中度抑郁症患者随机分为西药组（A组）、电针组（B组）、针药组（C组）,采用GE EXCITE II Signa 3.0T磁共振系统,PROBE-J序列进行单体素采集,感兴趣区分别置于左、右两侧海马和额叶。比较正常志愿者与3组患者治疗前后N－乙酰天门冬氨酸/胆碱（NAA/Cho）、N－乙酰天门冬氨酸/肌酸（NAA/Cr）和胆碱/肌酸（Cho/ Cr）值的差异。结果：治疗前三组患者双侧海马的NAA/Cr值较对照组减低,治疗后B组双侧海马、C组右侧海马的NAA/Cr值较治疗前增高（P<0.05）,C组左侧海马的NAA/Cr值较治疗前明显增高（P<0.01）。治疗前三组患者双侧额叶的Cho/ Cr值较对照组增高（P<0.05）,治疗后A组、B组双侧额叶的Cho/ Cr值较治疗前减低（P<0.05）,C组双侧额叶的Cho/ Cr值较治疗前明显减低（P<0.01）。结论：抑郁症患者双侧额叶、海马与正常成人相应部位的代谢物浓度存在差异,三种方案干预前后抑郁症患者脑功能活动各项指标的改变表明电针可通过多途径改善抑郁,而百优解的作用途径单一。     

磁共振波谱分析对轻微型肝性脑病患者的诊断价值

目的研究磁共振波谱分析(MRS)对轻微型肝性脑病(MHE)患者的诊断价值。方法应用3.0MR机对26例MHE患者进行扣带回和额叶的单体素点分辨自旋回波波谱序列扫描。计算N-乙酰天门冬氨酸(NAA)、肌酐(Cr)、胆碱(Cho)、肌醇(mI)和谷氨酰胺复合物(Glx)的峰下面积,计算NAA/Cr、Cho/Cr、mI/Cr、Glx/Cr的值,并与正常对照组比较。结果与正常对照组相比,MHE组扣带回和额叶的Cho/Cr、mI/Cr显著降低(P<0.01～0.001),Glx/Cr值显著升高(均P<0.005),NAA/Cr值差异无统计学意义(均P>0.05)。结论MHE患者MRS检查显示扣带回和额叶Cho、mI水平降低,Glx水平升高,MRS对MHE的诊断有显著价值。     

重复经颅磁刺激对酒依赖患者记忆功能及海马代谢的影响

目的 探讨重复经颅磁刺激(rTMS)对酒依赖患者戒断期记忆功能的影响及与海马代谢物水平变化的关系.方法 将38例男性戒断期酒依赖患者按随机数字表分为rTMS组和伪rTMS组,rTMS组给予1 Hz刺激4周,刺激部位为右侧背外侧前额叶皮质(DLPFC);伪rTMS组给予无效刺激.治疗前后分别评估言语记忆、视觉记忆,并采用氢质子磁共振波谱(1 H-MRS)检测双侧海马部位代谢物N-乙酰基天门冬氨酸(NAA)、胆碱化合物(Cho)和肌酸复合物(Cr).结果 (1)rTMS组治疗后言语记忆和视觉记忆评分较治疗前提高(P<0.05),而伪rTMS组治疗后记忆评分较治疗前差异无统计学意义(P>0.05).治疗后,rTMS组仅视觉记忆评分优于伪rTMS组,差异有统计学意义(P<0.01),而言语记忆未见明显改善(P>0.05).(2)rTMS组治疗后双侧海马NAA/Cr、Cho/Cr较治疗前升高(P<0.01),而伪rTMS组治疗前后双侧海马NAA/Cr、Cho/Cr的差异无统计学意义(P>0.05).治疗后,rTMS组双侧海马NAA/Cr、Cho/Cr高于伪rTMS组,差异有统计学意义(P<0.01).(3)左侧海马NAA/Cr、右侧海马Cho/Cr治疗后与治疗前的差值分别与言语记忆、视觉记忆评分呈正相关(P<0.01).结论 rTMS可以改善戒断期酒依赖患者的记忆功能,其可能机制与升高海马NAA/Cr和Cho/Cr有关.     

超高场强磁共振波谱分析对轻微型肝性脑病

目的： 研究MRS对轻微型肝性脑病(MHE)患者的诊断价值。方法　应用3.0 MR机对33例MHE患者和46例没有轻微型肝性脑病的肝硬化患者进行了扣带回和右侧前额叶的单体素点分辨自旋回波波谱序列扫描。计算N-乙酰天门冬氨酸(NAA)、肌酐(Cr)、胆碱(Cho)、肌醇(MI)和谷氨酰胺复合物(Glx)的峰下面积,计算NAA/Cr、Cho/Cr、MI/Cr、Glx/Cr,并与30例健康体检者（正常对照组）比较。33例在 MR检查前后一周内进行了静脉血氨水平测定。结果：与正常对照组相比,有轻微肝性脑病患者扣带回和右侧前额叶的Cho/Cr、MI/Cr 显著降低（P<0.01和 P0.05）,没有轻微肝性脑病的肝硬化患者与正常对照组比较MI/Cr有显著性差异（P0.05）。扣带回与右侧额叶的Glx/Cr比值与血氨浓度呈正相关,Cho/Cr 和MI/Cr的比值与血氨浓度呈负相关。 结论：MHE患者MRS检查显示扣带回和右侧前额叶Cho、MI水平降低,Glx水平升高;扣带回与右侧额叶的MRS指标与血氨之间存在相关关系,MRS对MHE的诊断有显著价值;扣带回和额叶可作为检测肝硬化患者脑改变的一个敏感部位。     

军人创伤后应激障碍治疗前后前额叶磁共振质子波谱的变化

目的探讨军人创伤后应激障碍(post-traumatic stress disorder,PTSD)患者治疗前后前额叶质子波谱的变化及临床疗效。方法纳入23例军人PTSD患者,并随机抽取某部25名健康官兵作为对照。采用前额叶氢质子磁共振波谱(proton magnetic resonance spectroscopy,1H-MRS)检查,测定两组前额叶N-乙酰基天门冬氨酸(N-acetylaspartate,NAA)、谷氨酰胺复合物(glutamate/glutamine,Glx)、胆碱复合物(choline-congtaining compounds,Cho)、肌醇(myo-inositol,m I)、肌酸复合物(creatine compounds,Cr)等化合物的含量。治疗前后采用创伤后应激障碍自评量表(post traumatic stress disorder self-rating scale,PTSD-SS)评估研究组症状。结果研究组治疗前左侧前额叶Cho/Cr与对照组存在统计学差异[(1.23±0.36)vs.(1.14±0.31),P0.05];研究组治疗前后左侧前额叶NAA/Cr存在统计学差异[(1.34±0.42)vs.(1.49±0.52),P0.05];相较治疗前,研究组治疗后PTSD-SS总分降低[(57.68±11.35)vs.(45.57±10.86)],各因子分亦均降低(P0.05)。结论军人PDST患者双侧前额叶均存在NAA/Cr、Cho/Cr等代谢物质的改变,且可能与患者精神症状的严重程度有关。     

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.     

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.     

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.     

Cellular origin and regulation of D- and L-serine in in vitro and in vivo models of cerebral ischemia

D-Serine is known to be essential for the activation of the N-methyl-D-aspartate (NMDA) receptor in the excitation of glutamatergic neurons, which have critical roles in long-term potentiation and memory formation. D-Serine is also thought to be involved in NMDA receptor-mediated neurotoxicity. The deletion of serine racemase (SRR), which synthesizes D-serine from L-serine, was recently reported to improve ischemic damage in mouse middle cerebral artery occlusion model. However, the cell type in which this phenomenon originates and the regulatory mechanism for D-/L-serine remain elusive. The D-/L-serine content in ischemic brain increased until 20 hours after recanalization and then leveled off gradually. The results of in vitro experiments using cultured cells suggested that D-serine is derived from neurons, while L-serine seems to be released from astroglia. Immunohistochemistry studies of brain tissue after cerebral ischemia showed that SRR is expressed in neurons, and 3-phosphoglycerate dehydrogenase (3-PGDH), which synthesizes L-serine from 3-phosphoglycerate, is located in astrocytes, supporting the results of the in vitro experiments. A western blot analysis showed that neither SRR nor 3-PGDH was upregulated after cerebral ischemia. Therefore, the increase in D-/L-serine was not related to an increase in SRR or 3-PGDH, but to an increase in the substrates of SRR and 3-PGDH.