The Effects of Genetic Changes and Neuroinflammation on Loneliness Feelings and Social Isolation: A Systematic Review

Loneliness arises from unmet emotional and social needs which causes several somatic and mental complications. According to several studies, a considerable relationship exists between genetics and loneliness. Since there is no comprehensive study in this regard, this investigation was designed to assess the effects of gene expression on feelings of loneliness. In this systematic review, the searching strategy was designed using MeSH-based keywords of "Impact", "Influence", "Gene", "Genetic", "Loneliness", and "Social isolation" in valid databases of PubMed, Scopus, ScienceDirect, Embase, web of Sciences (WoS), and Google Scholar. Following primary and secondary screenings, a qualitative assessment was applied by December 2024. Then, eligible studies were enrolled for data extraction and categorization. Following the initial searching, 392 papers were gathered. Then, 23 duplicate papers were merged using EndNote software. During primary and secondary screenings, 315 and 34 irrelevant papers were also excluded, respectively. Finally, following the exclusion of low-quality investigations (n = 10), 10 eligible papers were detected for data extraction. It was found that the specific gene regulation (CTRA and APOE-e4 genes expression) along with polymorphism (CHRNA4:rs1044396 and BDNF) can directly or indirectly cause the feeling of loneliness and social isolation. Reports showed that neuroinflammation and involvement of genetic changes in the Nucleus Accumbens can potentially lead to loneliness feelings. The relationship between gene expression and feelings of loneliness is multifaceted, involving both genetic predispositions and environmental influences. Research indicates that loneliness can trigger significant changes at the cellular level, affecting immune responses and overall health.