Neurogenetics and Epigenetics of Loneliness
Open accessAbstract
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.
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Blum et al identified genetic predisposition, mental health-related genetic overlap, epigenetic consequences of adverse childhood experiences, and hypodopaminergic reward deficiency states caused by early-life stress as factors influencing loneliness.
“Blum et al78 identified multiple factors influencing loneliness: (1) genetic predisposition; (2) mental health-related genetic overlap; (3) epigenetic consequences of adverse childhood experiences; and (4) hypodopaminergic reward deficiency states caused by early-life stress.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [78]
Loneliness contributes significantly to both psychological and physical morbidity.
“Loneliness, a growing public health concern, contributes significantly to both psychological and physical morbidity.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [78]
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Self-citationLoneliness-based impaired reward system pathway: Theoretical and clinical analysis and application
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Predicting the Risk of Loneliness in Children and Adolescents: A Machine Learning Study
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Exclusion and racial trauma: mental health costs for Canadian university students of color
Nepton, A., Farahani, H., Faber, S. C., & Williams, M. T. (2025) · Academia Mental Health and Well-Being · doi:10.20935/mhealthwellb7836 · Cited by 5 · see citing works
Personality and Psychoneuroimmunology: A Systems Biology Perspective
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Environmental epigenetics and the loneliness epidemic
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Life satisfaction as modifiable CVD prevention target: cross-cultural mediation in aging cohorts
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Self-citationCorrelates of Loneliness in Parkinson Disease During the COVID-19 Pandemic: A Longitudinal Study
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Social Isolation, Social Interaction, and Neuroticism: A Mendelian Randomization StudyPreprint
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- Authors
- Bowirrat, A., Elman, I., Dennen, C. A., Gondré-Lewis, M. C., Cadet, J. L., Khalsa, J., Baron, D., Soni, D., Gold, M. S., McLaughlin, T., Bagchi, D., Braverman, E. R., Ceccanti, M., Thanos, P. K., Modestino, E., Sunder, K., Jafari, N., Zeine, F., Badgaiyan, R. D., Barh, D., Makale, M., Murphy, K. T., & Blum, K.
- Affiliations
- Ariel University (IL)
- Cambridge Health Alliance (US)
- Thomas Jefferson University Hospital (US)
- National Institutes of Health (US)
- George Washington University (US)
- Western University of Health Sciences (US)
- Washington University in St. Louis (US)
- Texas Southern University (US)
- Regione Lazio (IT)
- University at Buffalo, State University of New York (US)
- Curry College (US)
- University of California, Riverside (US)
- California State University, Long Beach (US)
- Icahn School of Medicine at Mount Sinai (US)
- Universidade Federal de Minas Gerais (BR)
- University of California San Diego (US)
- Corresponding author
- Elman, Igor
- ORCID
- Venue
- Psychology Research and Behavior Management
- Publisher
- Informa UK Limited
- Published
- 2023-11
- Volume
- Volume 16
- Pages
- 4839-4857
- ISSN
- 1179-1578 (ISSN-L)
- PMC
- PMC10693768
- OpenAlex
- W4389146182
- Cited by
- 23
- References
- 176
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Psychology Research and Behavior Management (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (UL1TR001409)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Health › Health disparities and outcomes
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- loneliness, neurogenetics, epigenetics, social isolation, early life stress, maternal separation, childhood adversity, DNA methylation, mental health, dopamine, parental support, therapeutic target
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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