Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding.
Open accessAbstract
Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT(2A)) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT(2A) receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [(18)F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT(2A) receptor binding (p=0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT(2A) receptor binding was positively associated (p=0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT(2A) receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.
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Neuroticism is the personality trait most strongly associated with many forms of psychopathology.
“The personality trait neuroticism, reflecting an individual’s tendency to experience negative emotions, sensitivity to aversive cues, and insufficient ability to cope with stress, has been found to be the personality trait that is the most strongly associated with many forms of psychopathology (26–31)”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [28]
The Introduction (page not provided) describes neuroticism as a risk factor for depression, and the paper also links it to mood-disorder risk. It does not say neuroticism is the personality trait most strongly associated with psychopathology or establish an association across many forms of psychopathology. (LLM, conf=0.87)
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- Authors
- Frokjaer, V. G., Vinberg, M., Erritzoe, D., Baaré, W., Holst, K. K., Mortensen, E. L., Arfan, H., Madsen, J., Jernigan, T. L., Kessing, L. V., & Knudsen, G. M.
- Affiliations
- Copenhagen University Hospital (DK)
- Hvidovre Hospital (DK)
- University of Copenhagen (DK)
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2009-12-30
- Volume
- 35
- Issue
- 5
- Pages
- 1129-1137
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055406
- OpenAlex
- W2013558791
- Cited by
- 53
- References
- 52
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 4 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Lundbeckfonden (R62-2010-5364)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- mood disorders, familial risk, neuroticism, 5-HT2A receptor, life events, stress reactivity, personality traits, genetic risk, serotonergic neurotransmission, twins
- MeSH terms
- Adult, Family, Female, Frontal Lobe, Humans, Ketanserin, Limbic System, Male, Middle Aged, Personality, Personality Tests, Surveys and Questionnaires, Risk Factors, Sex Factors, Twins, Mood Disorders, Genetic Predisposition to Disease, Receptor, Serotonin, 5-HT2A, Positron-Emission Tomography, Young Adult
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