Choi Kwang Ho, Elashoff Michael, Higgs Brandon W, Song Jonathan, Kim Sanghyeon, Sabunciyan Sarven, Diglisic Suad, Yolken Robert H, Knable Michael B, Torrey E Fuller, Webster Maree J
Stanley Laboratory of Brain Research, 9800 Medical Center Dr. Bldg 2C, Rockville, MD 20850, USA.
BMC Psychiatry. 2008 Nov 7;8:87. doi: 10.1186/1471-244X-8-87.
Recent studies have shown similarities between schizophrenia and bipolar disorder in phenotypes and in genotypes, and those studies have contributed to an ongoing re-evaluation of the traditional dichotomy between schizophrenia and bipolar disorder. Bipolar disorder with psychotic features may be closely related to schizophrenia and therefore, psychosis may be an alternative phenotype compared to the traditional diagnosis categories.
We performed a cross-study analysis of 7 gene expression microarrays that include both psychosis and non-psychosis subjects. These studies include over 400 microarray samples (163 individual subjects) on 3 different Affymetrix microarray platforms.
We found that 110 transcripts are differentially regulated (p < 0.001) in psychosis after adjusting for confounding variables with a multiple regression model. Using a quantitative PCR, we validated a set of genes such as up-regulated metallothioneins (MT1E, MT1F, MT1H, MT1K, MT1X, MT2A and MT3) and down-regulated neuropeptides (SST, TAC1 and NPY) in the dorsolateral prefrontal cortex of psychosis patients.
This study demonstrates the advantages of cross-study analysis in detecting consensus changes in gene expression across multiple microarray studies. Differential gene expression between individuals with and without psychosis suggests that psychosis may be a useful phenotypic variable to complement the traditional diagnosis categories.
近期研究表明，精神分裂症和双相情感障碍在表型和基因型上存在相似性，这些研究推动了对精神分裂症和双相情感障碍之间传统二分法的持续重新评估。伴有精神病性特征的双相情感障碍可能与精神分裂症密切相关，因此，与传统诊断类别相比，精神病可能是一种替代表型。
我们对7个基因表达微阵列进行了跨研究分析，这些微阵列包括精神病患者和非精神病患者。这些研究包括在3种不同的Affymetrix微阵列平台上的400多个微阵列样本（163名个体受试者）。
我们发现，在使用多元回归模型调整混杂变量后，110个转录本在精神病患者中存在差异调节（p < 0.001）。通过定量PCR，我们验证了一组基因，如精神病患者背外侧前额叶皮质中上调的金属硫蛋白（MT1E、MT1F、MT1H、MT1K、MT1X、MT2A和MT3）和下调的神经肽（SST、TAC1和NPY）。
本研究证明了跨研究分析在检测多个微阵列研究中基因表达的共识变化方面的优势。有精神病和无精神病个体之间的差异基因表达表明，精神病可能是一个有用的表型变量，以补充传统诊断类别。
