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。     

精神分裂症阳性症状与脑质子波谱及事件相关电位的相关性

目的:探讨阳性症状为主型精神分裂症患者前额叶和丘脑氢质子磁共振波谱(1H-MRS)与事件相关电位的相关性。方法:78例7d内未使用抗精神病药及影响脑内乙酰胆碱神经递质药阳性症状为主型精神分裂症患者(研究组)及56名正常对照(对照组)。研究组在入组24h内采用多体素1H-MRS检测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),计算NAA/Cr和Cho/Cr值;同时检测事件相关电位P300(P300)和听觉诱发电位(AEP),并与对照组进行比较。结果:研究组NAA/Cr值左侧前额叶、左侧丘脑均低于对照组,差异有统计学意义[(1.40±0.35)vs(1.60±0.39),t=3.11,P<0.01;(1.48±0.33)vs(1.64±0.36),t=2.50,P<0.05]。研究组P300靶刺激P3(Cz、FPz)、非靶刺激NP3(Cz、FPz)与AEPP2(FPz)的潜伏期均高于对照组,靶刺激P3(Cz、FPz)、非靶刺激NP3(Cz、FPz)及AEPN1-P2(Cz、FPz)波幅均低于对照组,差异均有统计学意义(P<0.05或P<0.01)。研究组左侧前额叶NAA/Cr值与Cz点的P3潜伏期呈负相关(r=-0.32,P<0.05),与P3、N1-P2波幅呈正相关(r=0.32、0.34,P均<0.05);与FPz点P3、NP3、P2潜伏期呈负相关(r=-0.37、-0.40、-0.41,P均<0.01),与P3、NP3、N1-P2波幅呈正相关(r=0.33、0.33、0.35,P均<0.05)。结论:阳性症状为主型精神分裂症患者左侧前额叶NAA代谢失衡与认知功能损害有关,低水平的NAA浓度可能是认知功能损害的发病机制之一。     

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。     

精神分裂症患者质子磁共振波谱变化特点及与疗效、认知功能的相关分析

目的探讨不同疗效的精神分裂症患者前额叶、丘脑神经生化代谢物质的变化特点,及神经生化代谢物质与疗效和事件相关电位P300的相关性。方法对经非典型抗精神病药物治疗8周的171例精神分裂症患者,治疗前后分别采用多体素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),计算NAA/Cr值、Cho/Cr值;运用事件相关电位P300(P300)评估认知功能。运用阳性与阴性症状量表(PANSS)评定临床症状,以PANSS减分率评定疗效;根据PANSS减分率分为有效组(≥50%)、改善组(20%～49%)和无效组(<20%),比较不同疗效组上述脑代谢指标的变化。结果治疗后有效组(n=79)、改善组(n=71)和无效组(n=21)的左侧前额叶NAA/Cr变化值分别为(0.054±0.019)、(0.047±0.017)和(0.037±0.014),前者高于后两者,改善组高于无效组(P<0.05或P<0.01);有效组左、右侧丘脑NAA/Cr变化值均高于无效组(P均小于0.01)。左侧前额叶、左侧和右侧丘脑NAA/Cr变化值均与PANSS减分率呈正相关(r值分别为0.45、0.38、0.41,P均小于0.01)。左侧前额叶NAA/Cr变化值与靶刺激P2、P3潜伏期变化值成负相关(r值分别为-0.37,-0.33,P<0.01或P<0.05),与靶刺激P2、P3及非靶刺激P2波幅变化值成正相关(r值分别为0.42,0.38,0.36,P<0.01);左侧丘脑NAA/Cr变化值与靶刺激P2潜伏期变化值成负相关(r=-0.30,P<0.05),与靶刺激P2及非靶刺激P2波幅变化值成正相关(r值分别为0.40,0.35,P<0.01);右侧前额叶、右侧丘脑NAA/Cr变化值与靶刺激P2潜伏期变化值成负相关(r值分别为-0.33,-0.34,P<0.05),与波幅变化值成正相关(r值分别为0.34,0.32,P<0.05)。结论精神分裂症患者左侧前额叶和左侧丘脑NAA/Cr值变化与抗精神病药物疗效相关,与认知功能变化也存在相关性。     

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。     

男性首次发病精神分裂症患者治疗前后额叶的质子波谱研究

目的在体研究精神分裂症症状发生的神经生物学基础,探讨抗精神病药对额叶代谢物质的潜在影响。方法应用磁共振质子波谱(MRS)技术对10例男性首发精神分裂症患者(患者组)和10名男性正常对照者(对照组)检测额叶氮-乙酰天门冬氨酸(NAA)、胆碱复合物(CHO)、肌酸(Cr)。患者组入组后均予以第二代抗精神病药治疗,治疗第2个月时复查额叶~1H-MRS。每次~1H-MRS检查的同时,患者组各接受1次阳性和阴性症状量表(PANSS)评定、威斯康星卡片分类测试(WCST)评定。对照组仅进行1次WCST评定。结果多因素方差分析表明,治疗前患者组左、右侧额叶灰白质NAA/Cr均低于对照组[左侧白质：患者组1.87±0.30；对照组2.13±0.43。左侧灰质：患者组1.44±0.20；对照组1.67±0.32。右侧白质：患者组1.60±0.28；对照组2.09±0.41。右侧灰质：患者组1.35±0.25；对照组1.56±0.30],差异均有统计学意义(P均＜0.05)。患者组治疗前后NAA/Cr、CHO/Cr的差异均无统计学意义(P均＞0.05)。结论精神分裂症患者可能存在额叶神经元的损害。第二代抗精神病药短期治疗对精神分裂症患者额叶~1H-MRS代谢物水平无明显影响。     

联合1H-MRS 及T2 信号对精神分裂症前额叶皮质的研究

目的 联合磁共振质子波谱（1H-MRS）及T2 信号强度两种手段对首发精神分裂症患者前 额叶皮质进行研究,探讨其变化规律及潜在联系。方法 收集34 例首发未用药精神分裂症患者和健康 对照35 人。所有受试者分别行前额叶皮层的1H-MRS 及快速自旋回波T2 序列,分析精神分裂症患者前 额叶皮质的代谢指标及T2 信号强度的变化规律。并分析相关阳性指标与PANSS 评分之间的相关性。 结果 精神分裂症患者双侧额叶NAA/Cr 比值较对照组明显降低,差异有统计学意义（P＜ 0.05）;两组间 双侧额叶Cho/Cr比值差异无统计学意义（P ＞ 0.05）。精神分裂症患者双侧额叶上部磁共振T2 信号强度 较对照组明显增高,差异有统计学意义（t=2.07、2.18,P＜ 0.05）;精神分裂症患者左、右侧额叶中部及额 叶下部磁共振T2 信号强度与对照组相比差异均无统计学意义（P＞0.05）。精神分裂症患者左侧额叶上 部磁共振T2信号与PANSS阴性症状分数、PANSS总分呈正相关（r=0.57、0.49,P＜0.05）。结论 1H-MRS 及T2信号强度联合分析,可为精神分裂症临床早期诊断提供新的思路,借此思路或可解释首发精神分裂 症患者前额叶皮质的神经元代谢异常及病理改变两者之间的潜在联系。     

精神分裂症早发未用药患者脑质子磁共振波谱的异常特征

目的 探讨早发未经药物治疗的精神分裂症男性、女性患者前额叶和丘脑的神经生化代谢物质特点及差异.方法 纳入符合DSM-Ⅳ中精神分裂症诊断标准的早发患者44例(患者组),其中男25例(男性患者组)、女19例(女性患者组),以及健康对照者50名(对照组),其中男30名(男性对照组)、女20名(女性对照组).采用多体素质子磁共振波谱(hydrogen proton magnetic resonance spectroscopy,1 H-MRS)在患者入院24 h内抗精神病药治疗之前及健康对照入组时检测所有受试者前额叶和丘脑N-乙酰基天冬氨酸(N-acetylaspartate,NAA)、胆碱复合物(choline-congtaining compounds,Cho)与肌酸复合物(creatine compounds,Cr).采用PANSS评估患者临床症状.结果 男性与女性患者组之间PANSS总分及各因子分、病程的比较,差异均无统计学意义.男性患者组和女性患者组的NAA/Cr值:左侧前额叶(1.44±0.27和1.41 ±0.24)、右侧前额叶(1.41 ±0.28和1.39 ±0.26)及左侧丘脑(1.47±0.28和1.49±0.29)均分别低于同性别对照组(1.62±0.33和1.60±0.34、1.65±0.32和1.59 ±0.30、1.62 ±0.36和1.71±0.36),差异均有统计学意义(t值分别为2.18、2.06、2.23、2.28、2.20、2.09,均P＜0.05).男性与女性患者组之间1H-MRS各代谢指标比较,差异均无统计学意义,且2组前额叶、丘脑的NAA/Cr值、Cho/Cr值与PANSS总分及各因子分、病程间均无相关性(r=-0.37 ～0.27,P＞0.05).结论 早发未经药物治疗的精神分裂症患者可能存在双侧前额叶和左侧丘脑的神经元损害,这种损害与临床症状和病程均无直接关系,未发现存在性别差异.     

阳性症状为主型精神分裂症首次发病患者前额叶和海马磁共振质子波谱成像研究

目的 探讨阳性症状为主型精神分裂症首次发病患者前额叶和海马的磁共振质子波谱(1H-MRS)变化特点,为其病因学探讨提供线索.方法 对22例首次发病精神分裂症阳性症状为主型患者(患者组)和11名年龄、性别、受教育时间均匹配的正常对照者(对照组),应用2D 1H-MRS成像技术检测2组双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,分别计算NAA/Cr和Cho/Cr的比值;采用配对t检验、独立样本t检验进行统计分析.结果 (1)患者组左侧额叶白质NAA/Cr和Cho/Cr分别为(1.63±0.30)和(1.23±0.26),均低于对照组[(2.10±0.30)、(1.54±0.25)],右侧额叶白质NAA/Cr(1.70±0.34)低于对照组(1.97±0.34),差异有统计学意义(P<0.01和P<0.05);(2)双侧前扣带回皮质NAA/Cr、Cho/Cr值与对照组差异无统计学意义(P>0.05);(3)患者组右侧海马NAA/Cr(1.59±0.27)高于对照组(1.24±0.17),差异有统计学意义(P<0.01);(4)对照组内左侧额叶白质Cho/Cr(1.54±0.25)高于右侧(1.35±0.18),左侧海马NAA/Cr(1.45±0.28)高于右侧(1.24±0.17),差异均有统计学意义(P<0.05);(5)患者组内左侧海马NAA/Cr和Cho/Cr分别为(1.43±0.27)和(1.39±0.38),均低于右侧[(1.59±0.27)、(1.56±0.39)],差异有统计学意义(P<0.05).结论 首发精神分裂症阳性症状为主型患者的1H-MRS代谢物与正常人存在差异,提示阳性症状为主型患者存在双侧前额叶白质、海马的神经功能障碍.

Abstract：

Objective To identify the possible alteration of brain functioning in prefrontal lobes and hippocampus in the first-episode positive symptoms of schizophrenia using proton magnetic resonance spectroscopy (1H-MRS). Methods 1H-MRS was performed on prefrontal white matter, anterior cingulated cortex and hippocampus in 22 patients and 11 age-, sex-, and education-matched right-handed healthy controls. The ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr were calculated. Results The NAA/Cr and Cho/Cr ratios in the left prefrontal white matter in patients were lower than that in normal controls (patients, NAA/Cr 1. 63 ±0. 30; Cho/Cr 1. 23 ±0. 26; controls, NAA/Cr 2. 10 ±0. 30; Cho/Cr 1. 54 ± 0. 25, P<0. 01) , and NAA/Cr in the right prefrontal white matter was lower in patients than in controls (patients 1. 70 ± 0. 34; controls 1. 97 ± 0. 34, P<0. 05). There were no significant difference in NAA/Cr, Cho/Cr for the bilateral anterior cingulated cortex between patients and controls (P>0. 05). The ratio of NAA/Cr in the right hippocampus was significantly higher in patients than that in controls (patients 1. 59 ± 0. 27; controls 1. 24 ± 0. 17, P<0. 01). In addition, in healthy controls,Cho/Cr was significantly higher in the left prefrontal white matter than in the right (left 1. 54 ± 0. 25; right 1. 35 ±0. 18, P<0. 05) , and NAA/Cr in the left hippocampus was significantly higher than in the right (left 1. 45 ± 0. 28; right 1. 24 ± 0. 17, P<0. 05). While NAA/Cr and Cho/Cr in the left hippocampus were significantly lower than in the right hippocampus in schizophrenia patients (left, NAA/Cr 1.43 ± 0. 27;Cho/Cr 1.39 ±0.38; right, NAA/Cr 1.59 ±0.27; Cho/Cr 1.56 ±0.39, P<0.05). Conclusion There is the significant difference of manifestation of 1H-MRS between schizophrenia patients with positive symptoms and normal controls, which reflects neuronal dysfunction in the prefrontal lobes and hippocampus.     

精神分裂症患者前额叶和丘脑的质子磁共振波谱研究

Objective To identify the metabolite levels in prefrontal lobe and thalamus in patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). Methods Thirty-eighty schizophrenics and 38 normal controls were involved in this study. A multi-voxel 1H-MRS was given to all the subjects on prefrontal lobe and thalamus within 24 hours they got in hospital. The N-acetylaspartate (NAA), choline-congtaining compounds (Cho), and creatine compounds (Cr) were measured and the ratios of NAA/Cr, Cho/Cr and NAA/( Cho + Cr) were determined Results In left prefrontal lobe and bilateral thalamus, the NAA/Cr ratio in patients demonstrated lower than that in normal controls ( all P <0. 05). In left prefrontal lobe, the NAA/(Cho + Cr) ratio in patients showed lower than that in normal controls (0. 64 ±0. 13 vs. 0. 74±0. 22,t =2. 26, P<0. 05). Both in patients and in normal controls, there were no significant differences in NAA/Cr, Cho/Cr and NAA/(Cho + Cr) between the two sides (all P >0. 05). Conclusious Abnormalities in neuronal function and/or integrity are present in schizophrenics.There is no significantly lateralized asymmetry for metabolite levels such as NAA, Cho and Cr in either the schizophrenics or the controls.     

正常人丘脑质子磁共振波谱分析

背景：磁共振波谱使神经影像学从单纯形态学观察进入到分子水平上的探索,有研究利用磁共振波谱发现疾病发生时丘脑生化代谢物质与正常人存在差异。 目的：利用氢质子磁共振波谱(1H-MRS)观察正常人的丘脑代谢特点,为正常人及脑部疾患的相关治疗提供客观依据。 设计、时间及地点：自身对照,横断面调查,于2007-08/2008-08在解放军第九一中心医院影像中心完成。 对象：选择解放军第九一中心医院附近社区的精神正常的居民及学生共56名,男32名,女24名。所有受检者或其监护人均对调查方案知情同意,并签署知情同意书, 方法：采用1.5T超导型磁共振成像系统,入组24 h后采用多体素1H-MRS检测丘脑生化代谢物N-乙酰天冬氨酸、胆碱复合物与肌酸复合物。 主要观察指标：用随机软件测量N-乙酰天冬氨酸、胆碱复合物、肌酸复合物的峰下面积,以肌酸复合物峰为参照,计算机自动完成N-乙酰天冬氨酸/肌酸复合物值、胆碱复合物/肌酸复合物值、N-乙酰天冬氨酸/(胆碱复合物+肌酸复合物)值的计算。 结果：正常人丘脑1H-MRS左侧N-乙酰天冬氨酸/肌酸复合物、N-乙酰天冬氨酸/(胆碱复合物+肌酸复合物)高于右侧,胆碱复合物/肌酸复合物低于右侧,但差异但差异无显著性意义(P > 0.05)。经Pearson分析,丘脑双侧各观察指标与年龄均无相关性(P > 0.05);不同性别间比较,男性组左右两侧N-乙酰天冬氨酸/肌酸复合物、右侧胆碱复合物/肌酸复合物、左侧N-乙酰天冬氨酸/(胆碱复合物+肌酸复合物)均高于女性组,余观察指标低于女性组,但差异均无显著性意义(P > 0.05)。 结论：正常人丘脑代谢物双侧无差异,代谢物水平可能并不受性别和年龄的影响。     

Negative symptoms and hypofrontality in chronic schizophrenia.

Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms.     

Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study

INTRODUCTION: Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects. METHOD: Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured. RESULTS: There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites. CONCLUSIONS: The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.     

Positive and negative subtypes of schizophrenia. A follow-up study from India

98 schizophrenic patients who were initially studied to examine the concept of positive and negative subtyping, were followed up for a period ranging from 18 to 30 months. Follow-up data were available for 79 patients. The major findings of the study are significant reduction in positive symptom scores and the number of patients in the positive subtype of schizophrenia. The mixed subtype of schizophrenics increased in number and at follow-up there were significantly more mixed subtype schizophrenics who did not meet criteria for either the positive or negative subtype, i.e., who had little of either type of symptomatology. The number of schizophrenics categorized as negative subtype, as well as negative symptom scores did not change appreciably. The results of the study indicate that the negative symptoms seem to become more stable over a period of time.     

Striatal creatine and glutamate/glutamine in attention-deficit/hyperactivity disorder

OBJECTIVE: The glutamatergic prefrontal-striatal pathway has been implicated previously in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). We used short echo proton magnetic resonance spectroscopy (1H-MRS) to examine glutamate in the prefrontal cortex, left striatum, and, as a control area, the occipital lobe. METHOD: Thirteen treatment-na?ve ADHD children and 10 healthy comparison subjects participated. All were males between the ages of 6 to 11 years of age. Twelve ADHD subjects were scanned after 8 weeks of treatment. RESULTS: Striatal glutamate, glutamate/glutamine (Glx) and creatine concentrations were greater in the ADHD subjects at baseline as compared to controls. Only striatal creatine, not glutamate or Glx, was reduced after stimulant treatment in the ADHD patients. No significant differences between groups were noted in the remainder of the striatal metabolites or any of the occipital lobe or prefrontal cortex metabolites. CONCLUSIONS: These findings provide initial evidence of a striatal creatine/glutamatergic dysregulation in ADHD.     

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).     

Proton magnetic resonance spectroscopy of the medial prefrontal cortex in patients with deficit schizophrenia: preliminary report

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome. METHOD: The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex. RESULTS: The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients. CONCLUSIONS: As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.