Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.
Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.
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DOI：
10.1002/ajmg.b.31006
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发表时间：
2010-03-05
影响因子：
2.8
通讯作者：
Everall, Ian P.
中科院分区：
文献类型：
--
作者：
Bousman, Chad A.;Chana, Gursharan;Glatt, Stephen J.;Chandler, Sharon D.;Lucero, Ginger R.;Tatro, Erick;May, Todd;Lohr, James B.;Kremen, William S.;Tsuang, Ming T.;Everall, Ian P.
精神分裂症 (SCZ) 和双相情感障碍 (BPD) 是多基因疾病，许多基因导致其病因。这项研究的目的是寻找这些疾病以及精神病的失调的分子和细胞途径。我们对来自圣地亚哥（SCZ = 13，BPD = 9，对照 = 8）和台湾（SCZ = 11，BPD = 14，对照 = 16）的两个独立样本进行了基于血液的微阵列研究。将诊断组与对照组进行比较，并将有精神病史的受试者[PSYCH(+)：圣地亚哥(n = 6)，台湾(n = 14)]与没有精神病史的受试者进行比较[PSYCH(−)：圣地亚哥(n = 11)，台湾(n = 14)]。对逐个基因比较平均表达水平进行协方差分析，为每个诊断组的两个样本生成前 100 个显着失调的基因列表。基因列表被导入 Ingenuity Pathway Analysis (IPA) 软件中。结果显示，泛素蛋白酶体通路 (UPS) 在两个样本中均被列为 BPD 和精神病诊断组的十大典型通路，且偶然发生的可能性相当低 (P = 0.001)。在两个独立样本之间没有观察到这些通路中失调基因的重叠。研究结果提供了 BPD 和精神病中 UPS 失调的初步证据，并支持进一步研究 UPS 和其他分子和细胞通路，寻找 SCZ、BPD 和/或精神病的潜在生物标志物。
Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control = 8) and Taiwan (SCZ = 11, BPD = 14, control = 16). Diagnostic groups were compared to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n = 6), Taiwan (n = 14)] were compared to subjects without such history [PSYCH(−): San Diego (n = 11), Taiwan (n = 14)]. Analyses of covariance comparing mean expression levels on a gene-by-gene basis were conducted to generate the top 100 significantly dysregulated gene lists for both samples by each diagnostic group. Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical pathways for BPD and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence (P = 0.001). No overlap in dysregulated genes populating these pathways was observed between the two independent samples. Findings provide preliminary evidence of UPS dysregulation in BPD and psychosis as well as support further investigation of the UPS and other molecular and cellular pathways for potential biomarkers for SCZ, BPD, and/or psychosis.
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影响因子：
--
作者：
Schroeder A;Mueller O;Stocker S;Salowsky R;Leiber M;Gassmann M;Lightfoot S;Menzel W;Granzow M;Ragg T
通讯作者：
Ragg T
影响因子：
3.7
作者：
Huang JT;Leweke FM;Tsang TM;Koethe D;Kranaster L;Gerth CW;Gross S;Schreiber D;Ruhrmann S;Schultze-Lutter F;Klosterkötter J;Holmes E;Bahn S
通讯作者：
Bahn S
DOI：
10.1073/pnas.032069099
发表时间：
2002-04-02
影响因子：
11.1
作者：
Mimmack, ML;Ryan, M;Bahn, S
通讯作者：
Bahn, S
影响因子：
--
作者：
Merikangas, Kathleen R.;Akiskal, Hagop S.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
168.9
作者：
Tkachev, D;Mimmack, ML;Bahn, S
通讯作者：
Bahn, S