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 - Funding Information:
The authors declare no financial conflict of interest. This research was supported by Grant RO1MH063875 from the National Institute of Mental Health to Larry J. Siever and subsequently to Harold W. Koenigsberg. This publication was made possible by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).
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 -