Currently the leading cause of global disability, clinical depression is a heterogeneous condition characterised by low mood, anhedonia and cognitive impairments. Its growing incidence among young people, often co-occurring with self-harm, is of particular concern. We recently reported very high rates of depression among first year university students in Northern Ireland, with over 25% meeting the clinical criteria, based on DSM IV. However, the causes of depression in such groups remain unclear, and diagnosis is hampered by a lack of biological markers. The aim of this exploratory study was to examine DNA methylation patterns in saliva samples from individuals with a history of depression and matched healthy controls. From our student subjects who showed evidence of a total lifetime major depressive event (MDE, n = 186) we identified a small but distinct subgroup (n = 30) with higher risk scores on the basis of co-occurrence of self-harm and attempted suicide. Factors conferring elevated risk included being female or non-heterosexual, and intrinsic factors such as emotional suppression and impulsiveness. Saliva samples were collected and a closely matched set of high-risk cases (n = 16) and healthy controls (n = 16) similar in age, gender and smoking status were compared. These showed substantial differences in DNA methylation marks across the genome, specifically in the late cornified envelope (LCE) gene cluster. Gene ontology analysis showed highly significant enrichment for immune response, and in particular genes associated with the inflammatory skin condition psoriasis, which we confirmed using a second bioinformatics approach. We then verified methylation gains at the LCE gene cluster at the epidermal differentiation complex and at MIR4520A/B in our cases in the laboratory, using pyrosequencing. Additionally, we found loss of methylation at the PSORSC13 locus on chromosome 6 by array and pyrosequencing, validating recent findings in brain tissue from people who had died by suicide. Finally, we could show that similar changes in immune gene methylation preceded the onset of depression in an independent cohort of adolescent females. Our data suggests an immune component to the aetiology of depression in at least a small subgroup of cases, consistent with the accumulating evidence supporting a relationship between inflammation and depression. Additionally, DNA methylation changes at key loci, detected in saliva, may represent a valuable tool for identifying at-risk subjects.

中文翻译：

---

患有抑郁症的年轻人的甲基化组分析支持与免疫反应和银屑病的联系。

目前，临床抑郁症是导致全球残疾的主要原因，是一种以情绪低落、快感缺乏和认知障碍为特征的异质性疾病。它在年轻人中的发病率越来越高，通常与自残同时发生，尤其令人担忧。我们最近报告了北爱尔兰大学一年级学生的抑郁症发生率非常高，根据 DSM IV，超过 25% 的学生符合临床标准。然而，这些群体中抑郁的原因尚不清楚，并且由于缺乏生物标志物而阻碍了诊断。这项探索性研究的目的是检查来自有抑郁症病史和匹配的健康对照者的唾液样本中的 DNA 甲基化模式。来自我们的学生科目，他们显示出终生严重抑郁事件（MDE，n = 186）我们确定了一个小但不同的亚组（n = 30），基于自残和企图自杀的同时发生，具有更高的风险评分。导致风险升高的因素包括女性或非异性恋，以及情绪压抑和冲动等内在因素。收集唾液样本并比较一组密切匹配的高危病例（n = 16）和健康对照（n = 16）在年龄、性别和吸烟状况方面相似。这些表明整个基因组中 DNA 甲基化标记存在显着差异，特别是在晚期角质化包膜 (LCE) 基因簇中。基因本体分析显示免疫反应高度显着富集，特别是与炎症性皮肤病银屑病相关的基因，我们使用第二种生物信息学方法证实了这一点。然后，我们在实验室的案例中使用焦磷酸测序验证了表皮分化复合体的 LCE 基因簇和 MIR4520A/B 的甲基化增益。此外，我们通过阵列和焦磷酸测序发现 6 号染色体上 PSORSC13 基因座的甲基化缺失，证实了最近在自杀死亡者脑组织中的发现。最后，我们可以证明，在一个独立的青春期女性队列中，免疫基因甲基化的类似变化先于抑郁症的发作。我们的数据表明，至少在一小部分病例中，免疫成分与抑郁症的病因有关，这与支持炎症与抑郁症之间关系的越来越多的证据一致。此外，在唾液中检测到的关键位点的 DNA 甲基化变化，