Single-Dose of Testosterone and the MAOA VNTR Polymorphism Influence Emotional and Behavioral Responses in Men During a Non-social Frustration Task

Abstract

Previous studies suggest that testosterone and several neurotransmitters might interactively influence human aggression. The current study aimed to test potential interactions of a genetic variation linked to the catabolism of serotonin, dopamine, and norepinephrine and exogenous testosterone on the reaction towards non-social provocation. In total, 146 male participants were genotyped for a prominent polymorphism of the monoamine oxidase A (MAOA) gene resulting in a short and long variant. Participants completed a non-social frustration task after receiving either testosterone or a placebo gel in a double-blind setup. Participants performed a non-social frustration task, where they had to direct a virtually moving ball into a barrel by pulling a joystick (neutral block). During a frustration block, the joystick repeatedly did not respond to participants' reactions thereby causing failed trials to which participants reacted with increased anger and stronger pulling of the joystick. We analyzed the effect of testosterone administration on emotion and behavior in individuals who either carried a low (L) or high (H) activity MAOA variant. Testosterone administration increased provocation-related self-reported anger and abolished the association between trait aggression and joystick deflection in the frustration block. In MAOA-H carriers endogenous testosterone levels at baseline were associated with increased joystick deflection in both blocks. There was, however, no interaction of testosterone administration and genotype. Although preliminary, the results rather indicate independent influences of exogenous testosterone administration and MAOA, but support an interaction of endogenous testosterone levels and MAOA genetics in a frustration task. The administration of testosterone seems to act on the subjective emotional experience in a provoking situation, while endogenous testosterone levels increased pulling impulses only in carriers of the MAOA-H variant.

Aggression and criminality in androgen abusers

“…Of the 13 included studies, 4 are case studies [9 ▪▪ ,12–14], 4 are cross-sectional studies [15 ▪ –18 ▪ ], and two are meta-analyses of randomized controlled trials (RCTs) [19 ▪▪ ,20 ▪▪ ]. Additionally, two are systematic reviews on the effects of androgen therapy on aggression in transgender men [21 ▪ ] and the side effects of nandrolone decanoate [22], whereas one is a double-blind placebo-controlled RCT [23 ▪ ].…”

“…Only four studies [16 ▪ ,17 ▪ ,20 ▪▪ ,22] sampled women. Androgen abuse duration ranged from a few months [9 ▪▪ ] to 11 years [14] in the case reports, 1.33 [16 ▪ ] to 14.1 [18 ▪ ] years in the cross-sectional studies [15 ▪ ,17 ▪ ], one-time to 28 weeks in the meta-analyses of RCTs [19 ▪▪ ,20 ▪▪ ], and a one-time administration in the RCT [23 ▪ ].…”

DNA methylation and behavioral dysfunction in males with 47,XXY and 49,XXXXY: a pilot study

“…The beneficial effects associated with testosterone and behavior have been reported for more than a decade. Notably, testosterone treatment regulates both MAOA and AR expression [ 53 – 55 ] with one study reporting an interaction between testosterone treatment and an allelic variant in MAOA [ 56 ]. Generally, DNA methylation seems to be responsive to hormone treatment.…”

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

“…For example, TRT acts on the subjective emotional experience in a provoking situation, while endogenous testosterone levels increased pulling impulses only in carriers of the monoamine oxidase A variant with high activity due to a polymorphism of the MAOA gene (Wagels et al, 2020).…”

“…It is important to assess the effect of TRT on cerebral functions, since different responses have been demonstrated in subjects with high endogenous T levels compared to those with increased T due to TRT. For example, TRT acts on the subjective emotional experience in a provoking situation, while endogenous testosterone levels increased pulling impulses only in carriers of the monoamine oxidase A variant with high activity due to a polymorphism of the MAOA gene (Wagels et al, 2020).…”