Neurogenetics and Epigenetics of Loneliness

Abdalla Bowirrat, Igor Elman, Catherine A. Dennen, Marjorie C. Gondré-Lewis, Jean Lud Cadet, Jag Khalsa, David Baron, Diwanshu Soni, Mark S. Gold, Thomas J. McLaughlin, Debasis Bagchi, Eric R. Braverman, Mauro Ceccanti, Panayotis K. Thanos, Edward Justin Modestino, Keerthy Sunder, Nicole Jafari, Foojan Zeine, Rajendra D. Badgaiyan, Debmalya BarhMilan Makale, Kevin T. Murphy, Kenneth Blum

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4839-4857
Number of pages19
JournalPsychology Research and Behavior Management
StatePublished - 2023
Externally publishedYes


  • addiction
  • affective
  • alcohol
  • anti-reward
  • anxiety
  • cancer
  • cardiovascular
  • cognitive
  • depression
  • dopamine
  • genes
  • medical
  • motivation
  • reward deficiency
  • social isolation

ASJC Scopus subject areas

  • General Psychology
  • Psychiatry and Mental health


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