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

Journal Article (Journal Article)


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.


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.


These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men.

Full Text

Duke Authors

Cited Authors

  • Goetz, SMM; Tang, L; Thomason, ME; Diamond, MP; Hariri, AR; Carré, JM

Published Date

  • August 2014

Published In

Volume / Issue

  • 76 / 4

Start / End Page

  • 324 - 331

PubMed ID

  • 24576686

Pubmed Central ID

  • PMC9552187

Electronic International Standard Serial Number (EISSN)

  • 1873-2402

International Standard Serial Number (ISSN)

  • 0006-3223

Digital Object Identifier (DOI)

  • 10.1016/j.biopsych.2014.01.016


  • eng