Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans

Abstract Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A receptor (5-HT2AR) agonist radioligand [11C]Cimbi-36. In a randomized, double-blind, placebo-controlled, three-arm design, 23 healthy volunteers were PET scanned twice with [11C]Cimbi-36: at baseline and following double-blind assignment to one of three interventions (1) infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram preceded by oral dosing of the 5-HT1AR antagonist pindolol, (n = 8) (2) acute tryptophan depletion (ATD) (n = 7) and (3) placebo (n = 8). Two-sample t-tests revealed no significant group differences in percent change of neocortical [11C]Cimbi-36 binding from baseline to intervention between placebo and citalopram/pindolol (p = 0.4) or between placebo and ATD (p = 0.5). Notably, there was a significantly larger within-group variation in 5-HT2AR binding after intervention with citalopram/pindolol, as compared with placebo (p = 0.007). These findings suggest that neither ATD nor a combination of citalopram and pindolol elicit acute unidirectional changes in serotonin levels sufficient to be detected with [11C]Cimbi-36 PET in neocortex. We suggest that the large interindividual variation in 5-HT2AR binding after citalopram/pindolol reflects that after an acute SSRI intervention, individuals respond substantially different in terms of their brain serotonin levels. Our observation has a potential impact for the understanding of patient responses to SSRI

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT₄ receptor binding

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT(4) receptor (5-HT(4)R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT(4)R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT(4)R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT(4)R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT(4)R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT(4)R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT(4)R binding were associated with high trait aggression in males, but not in females

Trait aggression is associated with five-factor personality traits in males

BACKGROUND: Although aggression is conceptualized as a dimensional construct with violent behavior representing the extreme end of a spectrum, studies on the involvement of personality traits in human aggression have typically only included data representing a restricted spectrum of aggressive behaviors. METHODS: In the current study, we therefore examine whether trait aggression is associated with five‐factor model personality traits in an enriched sample of 259 men with a broad continuum of trait aggression, ranging from very low to very high including 39 incarcerated aggressive violent offenders. All participants completed the NEO Personality Inventory‐Revised (NEO PI‐R) and the Buss–Perry Aggression Questionnaire (BPAQ). The association between each of the five NEO PI‐R personality traits and trait aggression (BPAQ) was investigated using five linear regression models, covarying for group status, age and educational level. RESULTS: Higher BPAQ scores were positively associated with Neuroticism and negatively associated with Agreeableness and Conscientiousness. CONCLUSION: Our results indicate that those high in Neuroticism and low in Agreeableness and Conscientiousness are at higher risk of exhibiting aggressive behavior, underlining the relevance of these higher order personality traits in understanding aggressive behavior. We argue that studying individual personality differences should be offered a greater attention within violent and criminal behaviors