title: Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding.
abstract: 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.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Denmark. vibe@nru.dk
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: William
authors.initials: W
authors.lastname: Baaré
authors.forename: Klaus Kähler
authors.initials: KK
authors.lastname: Holst
authors.forename: Erik Lykke
authors.initials: EL
authors.lastname: Mortensen
authors.forename: Haroon
authors.initials: H
authors.lastname: Arfan
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D005190:Family; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D010551:Personality / Q000502:physiology*; D010556:Personality Tests; D049268:Positron-Emission Tomography; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires; D014427:Twins; D055815:Young Adult
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin