Department of Psychiatry, University Clinic of Navarra, Pamplona, Spain.
J Affect Disord. 2012 May;138(3):479-84. doi: 10.1016/j.jad.2012.01.040. Epub 2012 Feb 26.
As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP.
We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used.
Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p=0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p>0.05).
The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders.
Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.
由于双相情感障碍（BP）和注意缺陷多动障碍（ADHD）的标志物基因尚未完全确定，我们进行了全基因组分析，以寻找在 ADHD 和 BP 中差异表达的基因。
我们招募了 39 名患者（30 名 ADHD，9 名 BP），年龄 7 至 23 岁。为了评估精神科诊断，我们使用了基于 K-SADS-PL（DSM-IV）的半结构化访谈。从外周血中提取 RNA ，并使用 GeneChip® Human Genome U133-Plus 2.0（Affymetrix）进行分析。为了验证差异表达的基因，使用实时 PCR。
杂交和随后的统计分析发现 ADHD 和 BP 患者中有 502 个探针集表达存在显著差异。其中，82 个有高度显著差异。神经调节蛋白（NRG1）、组织蛋白酶 B 和 D（CTSB、CTSD）和前列腺素 D2-合酶（PTGDS）被选择用于半定量 mRNA 测定。与 BP 患者相比，ADHD 患者的 PTGDS 表达统计学上增加（p=0.01）。我们没有发现 NRG1、CTSB 和 CTSD 基因的这种差异表达（p>0.05）。
与 BP 患者相比，ADHD 患者的 PTGDS 基因编码蛋白表达增加，表明其与 ADHD 的不同病因可能存在关联。我们使用的实验方法至少部分通过检测直接涉及脑功能的蛋白质得到了验证，并为研究脑功能基因与精神疾病之间的联系提供了一种可能的方法。
明确表型的更大样本患者的确认需要进一步研究。
