Departments of Psychology and Psychiatry, Stony Brook University, Stony Brook, NY, USA.
Rush Alzheimer's Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Transl Psychiatry. 2018 Jan 10;8(1):2. doi: 10.1038/s41398-017-0086-2.
Subjective social isolation, loneliness, is associated with poor mental and physical health, but the underlying molecular mechanisms are poorly understood. Here we analyzed loneliness data collected on average 5 years ante-mortem and RNA gene expression at death in postmortem dorsolateral prefrontal cortex (DLPFC) from 181 participants in the Rush Memory and Aging Project (MAP), a longitudinal, prospective cohort study of common chronic conditions of aging. Our analytic protocol controlled for biographical variables (age, sex, education), psychological and health variables (depressive symptoms, interval between assessment and autopsy, slope of cognitive decline, AD pathology, presence of infarcts) and RNA integrity. Our results are based on a pre-ranked Gene Set Enrichment Analysis (GSEA) at FDR-corrected q-values <0.05, using these collections from the Molecular Signatures Database (v6.0 MSigDB): (1) Hallmarks, (2) Canonical, (3) Gene Ontology (GO), (4) Chemical and Genetic Perturbations, (5) Immunologic Signatures, (6) Oncogenic Signatures, and (7) Cancer Modules. We now report on 337 up-regulated and 43 down-regulated gene sets, among which the most significant ones were associated with Alzheimer's disease, psychiatric illness, immune dysfunction, and cancer. These gene sets constitute attractive targets for future studies into the molecular mechanisms by which loneliness exacerbates a wide range of neurodegenerative, psychiatric, and somatic illnesses.
主观社会隔离和孤独感与心理健康和身体健康状况不佳有关，但潜在的分子机制尚不清楚。在这里，我们分析了 Rush 记忆与衰老项目（MAP）中 181 名参与者平均在死前 5 年收集的孤独感数据以及死后死后外侧前额叶皮层（DLPFC）的 RNA 基因表达，MAP 是一项针对衰老常见慢性疾病的纵向前瞻性队列研究。我们的分析方案控制了传记变量（年龄、性别、教育程度）、心理和健康变量（抑郁症状、评估和尸检之间的间隔、认知能力下降的斜率、AD 病理学、梗死的存在）以及 RNA 完整性。我们的结果基于使用来自分子特征数据库（v6.0 MSigDB）的以下集合进行的预先排名基因集富集分析（GSEA）：（1）特征，（2）经典，（3）基因本体论（GO），（4）化学和遗传干扰，（5）免疫特征，（6）致癌特征和（7）癌症模块。现在，我们报告了 337 个上调和 43 个下调的基因集，其中最显著的基因集与阿尔茨海默病、精神疾病、免疫功能障碍和癌症有关。这些基因集为未来研究孤独感加剧广泛的神经退行性、精神和躯体疾病的分子机制提供了有吸引力的目标。
