Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects.
OBJECTIVE
Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT(1A) receptor, and sex hormones.


METHODS
Thirty-three healthy volunteers (16 women, aged 26.24 +/- 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl-(11)C]WAY-100635 to quantify 5-HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17beta-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions.


RESULTS
Statistical analyses revealed higher 5-HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5-HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03).


CONCLUSIONS
The present study provides first-time evidence for a specific interrelation between the 5-HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down-stream control due to higher amounts or activities of frontal 5-HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones.
Witte
A Veronica
AV
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Flöel
Agnes
A
Stein
Patrycja
P
Savli
Markus
M
Mien
Leonhard-Key
LK
Wadsak
Wolfgang
W
Spindelegger
Christoph
C
Moser
Ulrike
U
Fink
Martin
M
Hahn
Andreas
A
Mitterhauser
Markus
M
Kletter
Kurt
K
Kasper
Siegfried
S
Lanzenberger
Rupert
R
D000328:Adult; D000374:Aggression / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D010552:Personality Assessment; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012738:Sex Hormone-Binding Globulin; D044282:Receptor, Serotonin, 5-HT1A; D013739:Testosterone; D004958:Estradiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide