title: Testosterone rapidly increases neural reactivity to threat in healthy men: a novel two-step pharmacological challenge paradigm.
abstract: 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.
authors.affiliation: Department of Psychology, Wayne State University, Detroit, Michigan.
authors.forename: Stefan M M
authors.initials: SM
authors.lastname: Goetz
authors.affiliation: Department of Psychology, Wayne State University, Detroit, Michigan.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Tang
authors.affiliation: Merrill Palmer Skillman Institute, Wayne State University, Detroit, Michigan; Department of Pediatrics, Wayne State University, Detroit, Michigan.
authors.forename: Moriah E
authors.initials: ME
authors.lastname: Thomason
authors.affiliation: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.affiliation: 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.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
authors.affiliation: Department of Psychology, Wayne State University, Detroit, Michigan; Department of Psychology, Nipissing University, North Bay, Ontario, Canada. Electronic address: justinca@nipissingu.ca.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Carré
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D001774:Blood Chemical Analysis; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005149:Facial Expression; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D006727:Hormone Antagonists / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D012815:Signal Processing, Computer-Assisted; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D010100:Oxygen
keywords: Aggression; amygdala; androgens; anger; emotion; fMRI; testosterone