title: Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans.
abstract: BACKGROUND
  Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies.
  
  
  METHODS
  With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire.
  
  
  RESULTS
  Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths.
  
  
  CONCLUSIONS
  This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.
authors: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom. ml437@cam.ac.uk
authors: Michael V
authors: MV
authors: Lombardo
authors: Emma
authors: E
authors: Ashwin
authors: Bonnie
authors: B
authors: Auyeung
authors: Bhismadev
authors: B
authors: Chakrabarti
authors: Meng-Chuan
authors: MC
authors: Lai
authors: Kevin
authors: K
authors: Taylor
authors: Gerald
authors: G
authors: Hackett
authors: Edward T
authors: ET
authors: Bullmore
authors: Simon
authors: S
authors: Baron-Cohen
mesh_terms: D000328:Adult; D000649:Amniocentesis / Q000379:methods; D001519:Behavior / Q000502:physiology*; D002648:Child; D003463:Cues; D004644:Emotions / Q000502:physiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006803:Human Development / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017072:Neostriatum / Q000254:growth & development / Q000473:pathology; D058027:Neuropsychiatry / Q000379:methods; D009714:Nucleus Accumbens / Q000254:growth & development / Q000473:pathology; D010553:Personality Development; D010775:Photic Stimulation / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000378:metabolism / Q000523:psychology; D012201:Reward; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000378:metabolism*
chemical_list: D013739:Testosterone