孤独,两者的既定风险因素,精神和身体的发病率,是一个日益严重的公共卫生问题。然而,孤独感相关发病的神经生物学机制尚不明确.在这里,我们研究了基因和相关的DNA风险多态性变异的作用,这些变异通过遗传和表观遗传机制与孤独有关,因此可能指向特定的治疗靶标。搜索是在PubMed上进行的,Medline,和EMBASE数据库使用特定的医学主题词,如孤独和基因,神经和表观遗传学,上瘾,情感障碍,酒精,反奖励,焦虑,抑郁症,多巴胺,癌症,心血管,认知,多巴胺减少症,medical,动机,(神经)精神病理学,社会孤立,奖励不足。叙事文献综述产生了科学和临床证据的递归集合,随后在以下关键领域进行了总结和总结:(1)遗传前因:探索介导奖励的多基因,压力,免疫和其他重要的重要功能;(2)基因和心理健康:检查与人格特质和精神疾病相关的基因,以深入了解融合在孤独体验上的复杂互动网络;(3)表观遗传效应:调查由与负面童年经历相关的表观遗传甲基化驱动的孤独和社会隔离的情况;(4)神经相关:分析与孤独相关的情感状态和认知,重点是早期生活中的多巴胺缺乏例如,母性分离,强调父母在生命早期支持的重要性。各种(epi)遗传因素对个人的贡献的识别为创造创新的预防,诊断,以及应对持续孤独感的个体的治疗方法。与当前对孤独的理解相关的临床方面和治疗前景,讨论了在孤独相关发病率的背景下,强调基因和DNA风险多态性变异的相关性。
Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.