Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding

Vibe G Frokjaer (1) , Maj Vinberg (1) , David Erritzoe (1) , William Baare (1) , Klaus Kähler Holst (1) , Erik Lykke Mortensen (1) , Haroon Arfan (1) , Jacob Madsen (1) , Terry Jernigan (1) , Lars Vedel Kessing (1) , Gitte Moos Knudsen (1)

1 Rigshospitalet section 9201

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-HT2A) receptor binding. Here we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT2A 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 [18F]-altanserin positron emission tomography (PET). We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT2A 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-HT2A 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-HT2A 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.

Mots clés: Clinical or Preclinical; 5-HT; 5-HT2A; affective disorder; personality; PET; Biological Psychiatry; Serotonin; Depression; Unipolar/Bipolar; Imaging

Vibe G Frokjaer, Maj Vinberg, David Erritzoe, William Baare, Klaus Kähler Holst, et al.. Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding. Neuropsychopharmacology, 2009, n/a (n/a), pp.n/a-n/a. ⟨10.1038/npp.2009.218⟩. ⟨hal-00496256⟩