Brain Serotonin Synthesis in Adult Males Characterized by Physical Aggression during Childhood: A 21-Year Longitudinal Study

Abstract

BackgroundAdults exhibiting severe impulsive and aggressive behaviors have multiple indices of low serotonin (5-HT) neurotransmission. It remains unclear though whether low 5-HT mediates the behavior or instead reflects a pre-existing vulnerability trait.Methodology/Principal FindingsIn the present study, positron emission tomography with the tracer alpha-[11C]methyl-L-tryptophan (11C-AMT) was used to compare 5-HT synthesis capacity in two groups of adult males from a 21-year longitudinal study (mean age ± SD: 27.1±0.7): individuals with a history of childhood-limited high physical aggression (C-LHPA; N = 8) and individuals with normal (low) patterns of physical aggression (LPA; N = 18). The C-LHPA males had significantly lower trapping of 11C-AMT bilaterally in the orbitofrontal cortex and self-reported more impulsiveness. Despite this, in adulthood there were no group differences in plasma tryptophan levels, genotyping, aggression, emotional intelligence, working memory, computerized measures of impulsivity, psychosocial functioning/adjustment, and personal and family history of mood and substance abuse disorders.Conclusions/SignificanceThese results force a re-examination of the low 5-HT hypothesis as central in the biology of violence. They suggest that low 5-HT does not mediate current behavior and should be considered a vulnerability factor for impulsive-aggressive behavior that may or may not be expressed depending on other biological factors, experience, and environmental support during development.

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

“…Converging evidence from human clinical populations indicates that impulsive behaviors, especially those involving impulsive violent actions, are frequently associated with markers of serotonergic dysfunctions (Booij et al, 2010;Brown et al, 1979;Coccaro et al, 2010), confirming that this neurotransmitter plays a central role in selecting actions giving rise to motivationally significant reinforcers. On the other hand, the contributions of serotonin to decision makingFwhether impulsive or notFare likely to be complex and involve multiple receptor systems.…”

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

“…[147][148][149][150] Protective factors might also mitigate early influences on the neurochemical correlates of risk, including those mediated through 5-HT genes. 151 Multiple other biological adaptations that may promote resilience have also been identified. These include, but are not restricted to, high levels of dehydroepiandrosterone (DHEA), which has been shown to counter the effects of the stress hormone cortisol; high levels of testosterone; and high blood neuropeptide Y (NPY).…”

The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity

“…Notably, even though the observed differences in DNA methylation between those with high levels of aggression in childhood and those who had low levels were relatively small (5-8%), higher SLC6A4 methylation was associated with lower in vivo brain serotonin synthesis in the lateral left and right orbitofrontal cortex. Interestingly, these specific brain regions were also shown previously to have lower serotonin synthesis in those individuals with higher levels of aggressive behaviour during childhood (Booij et al, 2010).…”

“…Notably, even though the observed differences in DNA methylation between those with high levels of aggression in childhood and those who had low levels were relatively small (5-8%), higher SLC6A4 methylation was associated with lower in vivo brain serotonin synthesis in the lateral left and right orbitofrontal cortex. Interestingly, these specific brain regions were also shown previously to have lower serotonin synthesis in those individuals with higher levels of aggressive behaviour during childhood (Booij et al, 2010).It could be speculated that epigenetic alterations in 5-HT in the frontal-limbic regions are an underlying mechanism of how early environmental adversities translate into an increased risk for physical aggression. However, systematic studies investigating causal mechanisms of this potential association are lacking.…”

“…As mention above, maternal deprivation in monkeys is associated with altered 5-HIAA concentrations in the CSF but also with reduced 5-HTT and 5-HT 1A binding in the frontal-limbic regions (Ichise et al, 2006;Spinelli et al, 2010). Interestingly, serotonergic alterations in these brain regions have also been associated with impulsive/ aggressive behaviours (Booij et al, 2010;Siever, 2008). In humans, we found that maternal smoking during pregnancy was associated with lower brain 5-HT synthesis in the orbitofrontal cortex (OBFC) in adults .…”