Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, Toronto, Canada; Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil; Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo, SP, Brazil; University of Toronto, Toronto, Canada.
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, Toronto, Canada; University of Toronto, Toronto, Canada.
J Psychiatr Res. 2018 Jul;102:186-191. doi: 10.1016/j.jpsychires.2018.04.012. Epub 2018 Apr 13.
The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The "Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders" study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI.
这项研究的目的是比较精神分裂症（SZ）和心境障碍（MD）患者与健康对照组（HC）死后大脑中与 reelin 通路相关的基因表达，并探讨体重指数（BMI）作为潜在中介的作用。“精神分裂症和心境障碍死后 dlPFC 和海马体中的基因表达”研究拥有来自 SZ、MD 和 HC 个体的微阵列数据（其中 849 个样本来自 dlPFC，579 个来自海马体）。mRNA 数据使用 HumanHT-12 v4 BeadChip 阵列（Illumina）获得。多变量协方差分析用于研究组和相关协变量对 RELNm、NOTCH1、GRIN1m、GRIN3A、CAMK2Gm、CAMK2A、CAMK2Bm、CAMK2N2、GRIN2Bm、GRIN2A、CREBBPm、APOE、LDLR 和 DAB1 基因表达的主要影响。在 dlPFC 中，与 HC 相比，SZ 患者的 APOE 表达更高。与 HC 相比，MD 患者的 CAMK2A、CAMK2N2 和 GRIN2Bm 表达更高。此外，与 SZ 患者相比，MD 患者的 CAMK2N2 表达更高。RELN、CAMK2A、CAMK2N2 和 GRIN2A 的表达存在显著的组间 BMI 效应。在海马体中，与 HC 相比，MD 患者的 APOE 表达更低。这项研究的结果表明，与 reelin 通路相关的基因表达在 SZ 和 MD 患者与健康对照者之间可能不同，BMI 较大与更大的脆弱性相关。
