Gender, personality, and serotonin-2A receptor binding in healthy subjects

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Psychiatry Research (Impact Factor: 2.47). 12/2009; 181(1):77-84. DOI: 10.1016/j.pscychresns.2009.08.007
Source: PubMed


The vulnerability to mood disorders, impulsive-aggression, eating disorders, and suicidal behavior varies greatly with gender, and may reflect gender differences in central serotonergic function. We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT(2A) receptor binding in 21 healthy subjects using [18F]altanserin and PET neuroimaging. Binding potentials in pre-defined regions-of-interest (ROI) were calculated using the Logan graphical method, corrected for partial volume effects, and compared by gender with age co-varied. SPM analysis was used for voxel level comparisons. Altanserin binding (BP(P)) was greater in male than female subjects in the following nine ROIs: hippocampus (HIP) and Lt. HIP, lateral orbital frontal cortex (LOF) and Lt. LOF, left medial frontal cortex (Lt. MFC), left medial temporal cortex (Lt. MTC), left occipital cortex (Lt. OCC), thalamus (THL) and Lt. THL. Differences in Lt. HIP and Lt. MTL remained significant after Bonferroni correction. Gender differences were noted in the co-variation of psychological traits with BP(P) values in specific ROIs. Among males alone, aggression was negatively correlated with BP(P) values in Lt. LOF and Lt. MFC, and Suspiciousness positively correlated in LOF, Lt. LOF and Lt. MFC. Among female subjects alone, Negativism was positively correlated with BP(P) values in HIP, and Verbal Hostility in Lt. HIP. Altanserin binding in Lt. MTC was positively correlated with Persistence, with no significant gender effect. Gender differences in 5HT(2A) receptor function in specific ROIs may mediate expression of psychological characteristics such as aggression, suspiciousness and negativism. Future studies of 5HT(2A) receptor function and its relationship to behavior should control for gender.

Download full-text


Available from: Neale Scott Mason,
  • Source
    • "The TCI consists of 4 temperament scales (Harm Avoidance (HA), Novelty seeking (NS), Reward dependence (RD), Persistence (P)), and three character scales (Cooperativeness (CO), Self-directedness (SD) and Self Transcendence (ST)) [34]. This inventory has been used in a variety of studies examining psychobiological substrates of personality, including neurobiological, neuroimaging and genetic methods [12], [36], [37]. We extracted only the temperament dimension HA for our purposes (minimum score = 0, maximum score is 36). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The left and right amygdalae are key regions distinctly involved in emotion-regulation processes. Individual differences, such as personality features, may affect the implicated neurocircuits. The lateralized amygdala affective processing linked with the temperament dimension Harm Avoidance (HA) remains poorly understood. Resting state functional connectivity imaging (rsFC) may provide more insight into these neuronal processes. In 56 drug-naive healthy female subjects, we have examined the relationship between the personality dimension HA on lateralized amygdala rsFC. Across all subjects, left and right amygdalae were connected with distinct regions mainly within the ipsilateral hemisphere. Females scoring higher on HA displayed stronger left amygdala rsFC with ventromedial prefrontal cortical (vmPFC) regions involved in affective disturbances. In high HA scorers, we also observed stronger right amygdala rsFC with the dorsomedial prefrontal cortex (dmPFC), which is implicated in negative affect regulation. In healthy females, left and right amygdalae seem implicated in distinct mPFC brain networks related to HA and may represent a vulnerability marker for sensitivity to stress and anxiety (disorders).
    PLoS ONE 04/2014; 9(4):e95740. DOI:10.1371/journal.pone.0095740 · 3.23 Impact Factor
  • Source
    • "For example, low levels of 5-HT 2A binding potential have been found in the PFC of violent aggressive individuals (Meyer et al., 2008). In males, a negative correlation was found between 5-HT 2A binding in left orbital and medial frontal cortex and aggression severity (Soloff et al., 2010). In contrast with these data, prefrontal 5-HT 2 binding (as tested by 3 H ketanserin) has been found to be directly correlated with lifetime aggression scores in suicidal subjects (but not in their controls) (Oquendo et al., 2006); furthermore, 5-HT 2A receptor availability in the OFC has been recently correlated with a state measure of impulsive aggression (Rosell et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the mulifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and find new effective therapies for these conditions.
    Neuroscience 02/2013; 236:160-185. DOI:10.1016/j.neuroscience.2013.01.015 · 3.36 Impact Factor
  • Source
    • "Details concerning the MR and PET imaging procedures related to both [11C]WAY100635 and [18F]altanserin are described below, and have also been described previously [14,15,65-67] (see previous reports for discussion about the limitations, challenges and methodological attempts to minimize potential artifacts and biases related to these radioligands [25,67-71]). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography. 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low. Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.
    Biology of Mood and Anxiety Disorders 09/2011; 1(1):2. DOI:10.1186/2045-5380-1-2
Show more