Serum brain-derived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder

In this present work, it is aimed to demonstrate BDNF serum concentrations in patients with dysthymia and to compare them with BDNF serum concentrations in patients with major depressive disorder and healthy subjects. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Seventeen patients with dysthymia, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. The severity of depression was assessed with 17-item HAM-D. All subjects were asked to give their written consent. Blood samples were collected at baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA Kit (Promega; Madison, WI, USA), after dilution with the Block and Sample solution provided with the kit. The data were subjected to the analysis of variance. The BDNF serum concentrations of the dysthymia group (mean=28.9+/-9.2 ng/ml) were significantly higher than that of the major depressive disorder group (21.2+/-11.3 ng/ml) (p=0.002), and it was not different from the level of the control group (31.4+/-8.8 ng/ml). BDNF serum concentrations and HAM-D score did not have any significant correlation in the dysthymia and major depression groups (r=-0.276, p=0.086). The low level of BDNF in patients with dysthymic disorder seems to point out that BDNF changes in mood disorders are state-dependent and vary according to the severity of depressive episodes.     

Hippocampal loss of N-methyl-D-aspartate receptor subunit 1 mRNA in chronic temporal lobe epilepsy

The hippocampal distribution of mRNA for the N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR 1) was examined by non-radioactive in situ hybridization in 21 archival formalin-fixed and paraffin-embedded surgical specimens from patients with pharmacoresistant chronic epilepsy and in normal control specimens obtained at autopsy. Using the digoxigenin-labeling procedure, ribonucleotide probes were found to be significantly more sensitive than synthetic oligonucleotide probes. In normal autopsy specimens and in surgical specimens without Ammon's horn sclerosis there was intense NR 1 expression in a great majority of the dentate gyrus granular cells. Many neurons in the hippocampal pyramidal cell layer also revealed a strong signal intensity. The strata oriens and moleculare of Ammon's horn and the molecular layer of the dentate gyrus contained only few labeled neurons. In the subiculum and entorhinal cortex most neurons throughout various layers were positive. In hippocampal specimens of patients with chronic epilepsy there was a loss of NR 1-positive cells that was closely related to the overall neuronal loss in the respective specimen and to Ammon's horn sclerosis. These data suggest that the loss of NR 1 expression is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.     

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。     

颞叶癫痫患者注意网络的研究

目的探讨颞叶癫痫患者注意网络的状况及影响因素。方法连续收录2007年1月至2008年12月在我院就诊的44例颞叶癫痫患者,选择相匹配的健康志愿者40名作为对照研究。应用注意网络测试(attentional networks test,ANT)软件,评估被试者注意网络状况,比较两组注意网络各指标的差异,采用非条件Logistic分析受教育年限、病程等因素对注意网络指标的影响。结果与对照组比较,患者组的ANT平均反应时间较慢[患者组:(688.2±138.1)ms;对照组:(625.1±100.1)ms,t=2.06,P0.05];患者组ANT中执行功能效率显著下降[患者组:(155.7±57.0)ms;对照组:(108.0±33.8)ms,t=4.62,P0.01];两组MMSE、ANT的警觉功能与定向功能效率无统计学差异。非条件Logistic分析显示,存在脑电图痫性放电(95%CI:1.03～42.33,OR=6.603,P=0.043)为患者执行功能损害可能原因。结论初步证实颞叶癫痫患者存在注意网络的执行功能损害,痫性放电可能是导致患者注意执行功能损害的原因。     

颞叶癫痫患者海马苔藓纤维发芽的实验研究

目的观察颞叶癫痫病人海马齿状回和CA3区苔藓纤维出芽情况。方法癫痫组样本来自12例颞叶癫痫病例的手术切除标本包含海马齿状回和CA3区的脑组织，对照组脑组织样本来自4例非癫痫病的尸检脑组织。应用Timm组织化学染色方法在光镜和电镜水平进行海马结构苔藓纤维发芽的研究。结果光镜下癫痫组可见苔藓纤维穿越海马齿状回颗粒细胞层到达内分子层．CA3区也可见明显的苔藓纤维发芽。癫痫组CA3区和齿状回内分子层苔藓纤维发芽评分高于对照组．统计学上差异有显著性意义。电子显微镜下观察显示癫痫组患者齿状回内分子层可见到银标记的突触末端，主要和树突形成突触连接，所形成的突触为非对称性突触。结论颞叶癫痫可致海马齿状回和CA3区苔藓纤维发芽增加，这可能是难治性癫痫形成的重要机制。     

重度抑郁症症状缓解前后海马局部一致性研究

目的观察静息态下发作期重度抑郁症患者的海马功能,以及其在抗抑郁药物治疗达临床痊愈后的变化。方法对20例24项汉密尔顿抑郁量表(HAMD24)总分35分的重度抑郁症患者在治疗前、治疗8周达临床痊愈(HAMD24减分率≥75%)后进行静息态fMRI扫描,以性别、年龄、受教育程度匹配的20名正常人做对照组。采用局部一致性(regional homogeneity,ReHo)作为海马功能的测量指标。结果治疗前患者组较正常对照组左海马ReHo值增高,差异具有统计学意义(P0.05);但患者组治疗前与治疗后、治疗后与正常对照组的左海马ReHo值的差异均无统计学意义(P0.05)。患者组治疗前、治疗后、正常对照组中每两组间右海马ReHo值的差异均无统计学意义(P0.05)。结论重度抑郁症患者海马功能受损,存在侧化现象,经短期系统的抗抑郁药物治疗达临床痊愈后,这种损伤未见有效逆转。     

Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy

The expression of brain-derived neurotrophic factor and the alpha subunit of calcium/calmodulin-dependent protein kinase II mRNA in hippocampi obtained during surgical resections for intractable temporal lobe epilepsy were examined. Both calcium/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor are localized heavily within the hippocampus and have been implicated in regulating hippocampal activity (Kang and Schuman [1995] Science 267:1658-1662; Suzuki [1994] Intl J Biochem 26:735-744). Also, the autocrine and paracrine actions of brain-derived neurotrophic factor within the central nervous system make it a likely candidate for mediating morphologic changes typically seen in the epileptic hippocampus. Quantitative assessments of mRNA levels in epileptic hippocampi relative to autopsy controls were made by using normalized densitometric analysis of in situ hybridization. In addition, correlations between clinical data and mRNA levels were studied. Relative to autopsy control tissue, decreased hybridization to mRNA of the alpha subunit of calcium/calmodulin-dependent protein kinase II and increased hybridization to brain-derived neurotrophic factor mRNA were found throughout the granule cells of the epileptic hippocampus. There also was a significant negative correlation between the duration of epilepsy and the expression of mRNA for brain-derived neurotrophic factor. These results are similar qualitatively to those found in animal models of epilepsy and suggest that chronic seizure activity in humans leads to persistent alterations in gene expression. Furthermore, these alterations in gene expression may play a role in the etiology of the epileptic condition.     

Increased PLA2 activity in the hippocampus of patients with temporal lobe epilepsy and psychosis

Objective

The aim of this work was to investigate whether increased activity of the enzyme phospholipase A₂ (PLA₂) in the brain, as frequently reported in schizophrenia, is also related to psychosis in epilepsy. Our working hypothesis was based on the increased prevalence of schizophrenia-like psychosis in patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS), as compared to patients with other forms of epilepsy.

Methods

We determined PLA₂ activity in hippocampal tissue from 7 patients with TLE-MTS and psychosis, as compared to 9 TLE-MTS patients without psychosis. Hippocampal tissue was obtained from patients who underwent an anterior temporal lobectomy due to therapy-resistant epilepsy.

Results

We found that patients with TLE-MTS and psychosis had a significantly increased calcium-independent PLA₂ activity as compared to patients without psychosis (p = 0.016).

Conclusion

Our finding suggest that an increment in brain PLA₂ activity is not specific for schizophrenia, but rather may be associated to the manifestation of schizophrenia-like psychotic symptoms in general.     

精神分裂症患者脑源性神经营养因子基因多态性与临床症状的关系

背景 神经发育学说是精神分裂症发病机制的研究重点,脑源性神经营养因子（BDNF）在神经元发育过程中起重要作用,可能是精神分裂症的生物标志物之一。BDNF水平及其基因多态性在精神分裂症的发病机制中具有重要作用,但尚存争议。目的 分析精神分裂症患者BDNF水平与健康对照人群的差异,探讨BDNF单核苷酸多态性（SNPs）位点（rs11030101、rs2030324、rs6265）与BDNF水平的关系,并分析其与临床症状的关系,为精神分裂症的治疗提供参考。方法 采用病例对照研究,纳入2019年1月-2020年12月在中山市第三人民医院就诊的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）精神分裂症诊断标准的55例精神分裂症患者为研究对象,同期在中山市第三人民医院工作人员和社会人群中招募健康对照组31名。使用阳性和阴性症状量表（PANSS）评定精神分裂症患者的临床症状。采用酶联免疫吸附法（ELISA法）经酶标仪定标检测精神分裂症患者和对照组血清BDNF水平,采用聚合酶链式反应产物直接测序确定患者组和对照组BDNF的rs11030101、rs2030324、rs6265位点基因型。结果 患者组血清BDNF水平低于对照组,差异有统计学意义（t=-3.804,P<0.01）。临床症状方面,BDNF rs11030101位点不同基因型的患者PANSS总评分、兴奋敌对因子评分和抑郁焦虑因子评分差异均有统计学意义（t=2.022、Z=-2.696、-2.467,P<0.05或0.01）。不同位点的各基因型患者血清BDNF水平差异均无统计学意义（Z=1.483、F=2.584、0.417,P均>0.05）。结论 精神分裂症患者BDNF水平偏低。BDNF的rs11030101、rs2030324、rs6265位点多态性与血清BDNF水平水平无关,BDNF的rs11030101位点多态性可能会导致精神分裂症患者兴奋敌对、抑郁焦虑等临床症状。血清BDNF水平可能更多地取决于诊断效果而非基因多态性效应。     

5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression.

BACKGROUND: Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT(1A) receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT(1A) receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT(1A) receptor binding between TLE patients with and without MDD. For the first time, 5-HT(1A) receptor binding was measured in a sample large enough to permit sensitive comparisons between TLE patients with and without comorbid MDD diagnosed by clinical and structured psychiatric interviews. METHODS: Thirty-seven epilepsy patients with temporal lobe foci confirmed by ictal video-electroencephalogram (EEG) monitoring were recruited from the Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke. We performed interictal positron emission tomography scanning, with [(18)F]FCWAY, a fluorinated derivative of WAY100635, on a GE Medical Systems (Waukesha, Wisconsin) Advance scanner with continuous EEG monitoring. The 5-HT(1A) receptor binding was estimated by partial volume-corrected [(18)F]FCWAY V/f(1) values. RESULTS: In addition to decreased 5-HT(1A) receptor binding in the epileptic focus itself, comorbid MDD was associated with a significantly more pronounced reduction in 5-HT(1A) receptor binding in TLE patients, extending into non-lesional limbic brain areas outside the epileptic focus. Focus side and the presence of mesial temporal sclerosis were not associated with the presence of comorbid depression. CONCLUSIONS: Reductions in 5-HT(1A) receptor binding might help elucidate the neurobiological mechanisms underlying the TLE-MDD comorbidity.     

前颞叶和海马切除治疗难治性颞叶癫痫对认知功能影响的研究

目的 探讨前颞叶和海马切除治疗难治性颞叶癫痫对认知功能的影响.方法 19例难治性颞叶癫痫患者接受前颞叶和海马切除手术,手术前和手术后3、6月进行认知神经心理学测评以了解认知功能的变化.结果 19例难治件颞叶癫痫患者接受了前颞叶和海马切除术后取得了良好的疗效,术后1例有-过性的言语障碍,2例有-过性的欣快等精神症状.难治性颞叶癫痫患者存在严重的认知功能障碍(特别是智力、注意力、记忆功能障碍),前颞叶和海马切除手术没有加重认知功能障碍.在手术后6月一些认知功能反而有改善的趋势.结论 难治性颞叶癫痫患者存在认知功能障碍,采用前颞叶和海马切除能治愈或减少颞叶癫痫发作,并且对认知功能障碍有一定的改善作用.     

Different structural correlates for verbal memory impairment in temporal lobe epilepsy with and without mesial temporal lobe sclerosis

Objectives: Memory impairment is one of the most prominent cognitive deficits in temporal lobe epilepsy (TLE). The overall goal of this study was to explore the contribution of cortical and hippocampal (subfield) damage to impairment of auditory immediate recall (AIMrecall), auditory delayed recall (ADMrecall), and auditory delayed recognition (ADMrecog) of the Wechsler Memory Scale III (WMS‐III) in TLE with (TLE–MTS) and without hippocampal sclerosis (TLE‐no). It was hypothesized that volume loss in different subfields determines memory impairment in TLE–MTS and temporal neocortical thinning in TLE‐no. Methods: T1 whole brain and T2‐weighted hippocampal magnetic resonance imaging and WMS‐III were acquired in 22 controls, 18 TLE–MTS, and 25 TLE‐no. Hippocampal subfields were determined on the T2 image. Free surfer was used to obtain cortical thickness averages of temporal, frontal, and parietal cortical regions of interest (ROI). MANOVA and stepwise regression analysis were used to identify hippocampal subfields and cortical ROI significantly contributing to AIMrecall, ADMrecall, and ADMrecog. Results: In TLE–MTS, AIMrecall was associated with cornu ammonis 3 (CA3) and dentate (CA3&DG) and pars opercularis, ADMrecall with CA1 and pars triangularis, and ADMrecog with CA1. In TLE‐no, AIMrecall was associated with CA3&DG and fusiform gyrus (FUSI), and ADMrecall and ADMrecog were associated with FUSI. Conclusion: The study provided the evidence for different structural correlates of the verbal memory impairment in TLE–MTS and TLE‐no. In TLE–MTS, the memory impairment was mainly associated by subfield‐specific hippocampal and inferior frontal cortical damage. In TLE‐no, the impairment was associated by mesial–temporal cortical and to a lesser degree hippocampal damage. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Hippocampal neuronal density in temporal lobe epilepsy with and without gliomas

Summary The majority of patients with temporal lobe epilepsy show hippocampal sclerosis, which pathologically represents neuronal loss and gliosis. We studied volumetric neuronal density on a representative mid to mid-posterior level slice of hippocampi surgically removed from intractable temporal lobe epilepsy cases, and compared the results between 25 non-tumor epilepsy (NTE) cases and 5 tumor-associated epilepsy (TAE) cases. Eleven age-matched non-epileptic autopsy cases were studied as controls. Cells were counted in the CA1 through CA4 fields and the stratum granulosum of the dentate fascia. In NTE every hippocampal field showed statistically significant loss of neurons, the neuronal density in each field ranging from 35% to 50% of that of control. The mean neuronal density between the TAE and NTE groups also showed statistically significant differences in all hippocampal fields. The neuronal density of hippocampal fields of NTE ranged from 43% to 58% of that of TAE. Tumor-associated epilepsy cases, however, failed to show any statistically significant deviation from the control in their neuronal density. The etiology of the difference in neuronal density between the TAE and NTE groups is discussed.Supported by NIH grant NS06208     

Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y

Model studies on animal seizures have proposed potential involvement of the neurotrophins, BDNF and NGF, in human epilepsy. However, their biological significance in this disease itself remains to be evaluated. Here we demonstrate that patients with intractable temporal lobe epilepsy show a marked increase in protein levels of BDNF (2.6-fold, p<0.01) but not other neurotrophins. Moreover, the specific BDNF increase was significantly correlated with contents of neuropeptide Y. Thus, these results indicate the activity-dependent expression of BDNF in human subjects and its potential contribution to the pathophysiology of human epilepsy via neuropeptide Y.     

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor κB (NFκB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control.
Method: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors.
Results: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels.
Discussion: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.     

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.     

Predictors of depressive symptoms at hospital discharge in patients with major depressive disorder

Abstract

Objective. Often patients with major depressive disorder (MDD) leave the hospital with continued significant symptomatology. This study sought to evaluate demographic, clinical, and psychosocial predictors of the presence of clinically significant depressive symptoms, defined as a Modified Hamilton Rating Scale for Depression score of ≥ 14, immediately following hospitalization for MDD. Methods. The study enrolled 135 patients with MDD as part of a larger clinical trial investigating the efficacy of post-hospitalization pharmacologic and psychosocial treatments for depressed inpatients. Structured clinical interview and self-report data were available from 126 patients at hospital admission and discharge. Results. Despite the significant decreases in depressive symptoms over the course of hospitalization, 91 (72%) displayed clinically significant depressive symptoms at discharge. Multivariate logistic regression analysis revealed that female sex, earlier age of onset, and poorer social adjustment were unique predictors of symptom outcome. Conclusions. Results suggest that a large proportion of patients leave the hospital with continued significant symptomatology, and the presence of such symptoms following hospitalization for MDD is likely to be explained by a combination of factors.     

Voxel-based T2 relaxation rate measurements in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis

INTRODUCTION: Quantitative measurements of T(2) relaxation in the hippocampus for focus lateralization in mesial temporal lobe epilepsy (mTLE) are well established. Less is known to what degree such relaxation abnormalities also affect regions beyond the ipsilateral hippocampus. Therefore, the aim of this study was to characterize extent and distribution pattern of extrahippocampal relaxation abnormalities in TLE with (TLE-MTS) and without MRI evidence of mesial-temporal sclerosis (TLE-no). METHODS: Double spin echo images (TE1/2: 20/80 ms) acquired in 24 TLE-MTS and 18 TLE-no were used to calculate relaxation rate maps. These maps were analyzed by SPM2 and by selecting regions of interest (ROI) in the hippocampus and several extrahippocampal brain regions. RESULTS: In TLE-MTS, the results of the SPM and ROI analysis were in good agreement and showed the most severe relaxation rate decreases in the ipsilateral hippocampus but also in other ipsilateral temporal regions, orbitofrontal, and parietal regions and to a lesser degree in contralateral frontal regions. The relaxation rate decreases in TLE-no were confined to small regions in the ipsilateral anterior inferior and medial temporal lobe in the SPM analysis while ROI analysis showed additional regions in the ipsilateral hippocampus, amygdala, and anterior cingulate. CONCLUSION: TLE-MTS showed extensive, widespread but predominantly ipsilateral temporal and also extratemporal T(2) relaxation rate decreases. In contrast, the findings of the SPM and ROI analyses in TLE-no suggested that if relaxation rate decreases are present, they are less uniform and generally milder than in TLE-MTS. This further supports the hypothesis that TLE-no is a distinct clinicopathological entity from TLE-MTS and probably heterogeneous in itself.     

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real‐time PCR to quantify the expression of GABA_A (subunits α1, β1, β2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in α1, β1, and β2 subunits of GABA_A receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. © 2010 Wiley Periodicals, Inc., Inc.