TY - JOUR
T1 - Serotonin transporter availability in physically aggressive personality disordered patients
T2 - associations with trait and state aggression, and response to fluoxetine
AU - Rosell, Daniel R.
AU - Slifstein, Mark
AU - Thompson, Judy
AU - Xu, Xiaoyan
AU - Perez-Rodriguez, M. Mercedes
AU - McClure, Margaret M.
AU - Hazlett, Erin A.
AU - New, Antonia S.
AU - Nabulsi, Nabeel
AU - Huang, Yiyun
AU - Carson, Richard E.
AU - Siever, Larry S.
AU - Abi-Dargham, Anissa
AU - Koenigsberg, Harold W.
N1 - Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/2
Y1 - 2023/2
N2 - 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 [11C]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 [11C]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 [11C]DASB in IED patients. Greater baseline VST [11C]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.
AB - 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 [11C]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 [11C]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 [11C]DASB in IED patients. Greater baseline VST [11C]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.
KW - Aggression
KW - Anterior cingulate cortex
KW - Callousness
KW - Childhood trauma
KW - DASB
KW - Fluoxetine
KW - Intermittent explosive disorder
KW - Positron emission tomography
KW - Serotonin transporter
KW - Ventral striatum
UR - http://www.scopus.com/inward/record.url?scp=85146225231&partnerID=8YFLogxK
U2 - 10.1007/s00213-022-06306-2
DO - 10.1007/s00213-022-06306-2
M3 - Article
C2 - 36640190
AN - SCOPUS:85146225231
SN - 0033-3158
VL - 240
SP - 361
EP - 371
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2
ER -