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 ¼ 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 ¼ 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.

Effects of serotonin-2A receptor binding and gender on personality traits and suicidal behavior in borderline personality disorder

“…Increased cortical binding to the serotonin-2A receptor has been reported in some small sample studies of postmenopausal women following replacement hormone therapy (Moses et al, 2000; Kugaya et al, 2003), though not in other studies of hormonal contraception or replacement therapy (Frokjaer et al, 2008). A positive correlation between cortical serotonin-2A receptor binding and plasma estradiol levels has been reported in healthy men, with no independent effects for testosterone (Frokjaer et al, 2010). Future studies should sample sex hormones at the time of PET study to control for this variable.…”

The Association Between Negative Affect and Prescription Opioid Misuse in Patients With Chronic Pain: The Mediating Role of Opioid Craving

“…For example, previous studies have found that NA may enhance drug craving and the likelihood of drug abuse through increased noradrenergic and dopaminergic activity in cortical and subcortical mesolimbic areas. 48,71,72 Interestingly, NA has also been found to be associated with decreased central serotonergic (5-HT) activity, 1,29,31,32,41 one of the main neurotransmitter systems involved in the regulation of craving and drug use. In previous studies, decreased 5-HT activity has been found to be associated with enhanced self-reports of craving and with an increased likelihood of drug abuse in patients with various forms of drug problem.…”

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

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