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Biol Psychiatry. 2014 Aug 15;76(4):324-31. doi: 10.1016/j.biopsych.2014.01.016. Epub 2014 Jan 29.

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

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Department of Psychology, Wayne State University, Detroit, Michigan.
Merrill Palmer Skillman Institute, Wayne State University, Detroit, Michigan; Department of Pediatrics, Wayne State University, Detroit, Michigan.
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
Department of Pediatrics, Wayne State University, Detroit, Michigan; Department of Psychology and Neuroscience, Duke University, Durham, North Carolina; Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina.
Department of Psychology, Wayne State University, Detroit, Michigan; Department of Psychology, Nipissing University, North Bay, Ontario, Canada. Electronic address:



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.


Aggression; amygdala; androgens; anger; emotion; fMRI; testosterone

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