Testosterone Rapidly Increases Neural Reactivity to Threat in Healthy Men: A Novel Two-Step Pharmacological Challenge Paradigm

Journal article

Goetz, Stefan; Lingfei Tang; Moriah E. Thomason; Michael P. Diamond; Ahmad R. Hariri & Justin M. Carré (2014) Testosterone Rapidly Increases Neural Reactivity to Threat in Healthy Men: A Novel Two-Step Pharmacological Challenge Paradigm, Biological Psychiatry 76 (4): 324–331.

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Previous research suggests that testosterone (T) plays a key role in shaping competitive and aggressive behavior in humans, possibly by modulating threat-related neural circuitry. However, this research has been limited by the use of T augmentation that fails to account for baseline differences and has been conducted exclusively in women. Thus, the extent to which normal physiologic concentrations of T affect threat-related brain function in men remains unknown.

In the current study, we use a novel two-step pharmacologic challenge protocol to overcome these limitations and to evaluate causal modulation of threat- and aggression-related neural circuits by T in healthy young men (n = 16). First, we controlled for baseline differences in T through administration of a gonadotropin releasing hormone antagonist. Once a common baseline was established across participants, we then administered T to within the normal physiologic range. During this second step of the protocol we acquired functional neuroimaging data to examine the impact of T augmentation on neural circuitry supporting threat and aggression.

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