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Citation
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Rosell DR, Slifstein M, Thompson J, Xu X, Perez-Rodriguez MM, McClure MM, Hazlett EA, New AS, Nabulsi N, Huang Y, Carson RE, Siever LS, Abi-Dargham A, Koenigsberg HW. Psychopharmacology 2023; ePub(ePub): ePub. |
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Abstract
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RATIONALE: Characterizing the neuroanatomical basis of serotonergic abnormalities in severe, chronic, impulsive aggression will allow for rational treatment selection, development of novel therapeutics, and biomarkers to identify at-risk individuals.
OBJECTIVES: The aim of this study is to identify associations between regional serotonin transporter (5-HTT) availability and trait and state aggression, as well as response to the anti-aggressive effects of fluoxetine.
METHODS: We examined 5-HTT availability using positron emission tomography (PET) imaging with [(11)C]DASB in personality disordered patients with current physical intermittent explosive disorder (IED; n = 18), and healthy comparison participants (HC; n = 11), in the anterior cingulate cortex (ACC), amygdala (AMY), ventral striatum (VST), and midbrain (MID). After PET imaging, IED patients were treated with fluoxetine 20 mg daily (n = 9) or placebo (n = 6) for 12 weeks. Trait and state aggression, trait callousness, and childhood trauma were assessed.
RESULTS: In IED patients, trait aggression was positively associated with [(11)C]DASB binding in the ACC and VST; covarying for trait callousness and childhood trauma enhanced these correlations. Baseline state aggression was positively correlated with ACC [(11)C]DASB in IED patients. Greater baseline VST [(11)C]DASB binding predicted greater decreases in state aggression with fluoxetine treatment.
CONCLUSIONS: Consistent with prior reports, ACC 5-HTT is related to trait aggression, and adjusting for factors related to proactive (callousness) and reactive (childhood trauma) aggression subtypes further resolves this relationship. Novel findings of the study include a better understanding of the association between regional 5-HTT availability and state aggression, and the involvement of VST 5-HTT with trait aggression, and with the anti-aggressive effects of fluoxetine.
Language: en |