Testosterone rapidly increases neural reactivity to threat in healthy men: A novel two-step pharmacological challenge paradigm

Stefan M.M. Goetz, Lingfei Tang, Moriah E. Thomason, Michael P. Diamond, Ahmad R. Hariri, Justin M. Carré

Research output: Contribution to journalArticlepeer-review

120 Scopus citations


Background 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. Methods 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. Results Gonadotropin releasing hormone antagonism successfully reduced circulating concentrations of T and brought subjects to a common baseline. Administration of T rapidly increased circulating T concentrations and was associated with heightened reactivity of the amygdala, hypothalamus, and periaqueductal grey to angry facial expressions. Conclusions These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men.

Original languageEnglish (US)
Pages (from-to)324-331
Number of pages8
JournalBiological Psychiatry
Issue number4
StatePublished - Aug 15 2014


  • Aggression
  • amygdala
  • androgens
  • anger
  • emotion
  • fMRI
  • testosterone

ASJC Scopus subject areas

  • Biological Psychiatry


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