The Relationship Between Impulsivity Traits and In Vivo Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in Healthy Individuals: A Double-Tracer PET Study with C-11 DASB and C-11 MDL100907

To elucidate the potential roles of presynaptic and postsynaptic serotonergic activity in impulsivity traits, we investigated the relationship between self-reported impulsiveness and serotonin transporter (5-HTT) and 5-HT2A receptors in healthy individuals. In this study, 26 participants completed 3-Tesla magnetic resonance imaging and positron emission tomography with [¹¹C]DASB and [¹¹C]MDL100907. To quantify 5-HTT and 5-HT2A receptor availability, the binding potential (BP_ND) of [¹¹C]DASB and [¹¹C]MDL100907 was derived using the simplified reference tissue model with cerebellar gray matter as the reference region. The participants' impulsivity levels were assessed using the Barratt Impulsiveness Scale-11 (BIS-11). The region of interest (ROI)-based partial correlation analysis with age, sex, and temperament traits as covariates revealed a significant positive correlation between non-planning impulsiveness and [¹¹C]MDL100907 BP_ND in the caudate (CAU) at Bonferroni-corrected <i>p</i> < 0.0045. Non-planning impulsiveness was also positively correlated with [¹¹C]MDL100907 BP_ND in the prefrontal cortex (PFC), ventromedial PFC, orbitofrontal cortex (OFC), insula (INS), amygdala (AMYG), putamen, ventral striatum, and thalamus, and the total score of BIS-11 was positively correlated with [¹¹C]MDL100907 BP_ND in the OFC, INS, AMYG, and CAU at uncorrected <i>p</i> < 0.05. Motor impulsiveness had a positive correlation with [¹¹C]DASB BP_ND in the CAU at uncorrected <i>p</i> < 0.05. Our results suggest that impulsivity traits, characterized by focusing on the present moment without considering future consequences, may be involved in serotonergic neurotransmission, particularly 5-HT2A receptor-mediated postsynaptic signaling in the CAU, which plays an important role in cognitive processes related to executive function, judgment of alternative outcomes, and inhibitory control.