Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

Michael V. Lombardo, Emma Ashwin, Bonnie Auyeung, Bhismadev Chakrabarti, Meng-chuan Lai, Kevin Taylor, Gerald Hackett, Edward T. Bullmore, Simon Baron-cohen

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)839-847
JournalBiological Psychiatry
Volume72
Issue number10
DOIs
Publication statusPublished - 15 Nov 2012

Fingerprint

Fetal Development
Reward
Testosterone
Cues
Caudate Nucleus
Putamen
Nucleus Accumbens
Amygdala
Emotions
Choice Behavior
Avoidance Learning
Punishment
Amniotic Fluid
Sex Characteristics
Fear
Magnetic Resonance Imaging
Pregnancy

Cite this

Lombardo, M. V., Ashwin, E., Auyeung, B., Chakrabarti, B., Lai, M., Taylor, K., ... Baron-cohen, S. (2012). Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans. Biological Psychiatry, 72(10), 839-847. https://doi.org/10.1016/j.biopsych.2012.05.027

Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans. / Lombardo, Michael V.; Ashwin, Emma; Auyeung, Bonnie; Chakrabarti, Bhismadev; Lai, Meng-chuan; Taylor, Kevin; Hackett, Gerald; Bullmore, Edward T.; Baron-cohen, Simon.

In: Biological Psychiatry, Vol. 72, No. 10, 15.11.2012, p. 839-847.

Research output: Contribution to journalArticle

Lombardo, MV, Ashwin, E, Auyeung, B, Chakrabarti, B, Lai, M, Taylor, K, Hackett, G, Bullmore, ET & Baron-cohen, S 2012, 'Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans', Biological Psychiatry, vol. 72, no. 10, pp. 839-847. https://doi.org/10.1016/j.biopsych.2012.05.027
Lombardo, Michael V. ; Ashwin, Emma ; Auyeung, Bonnie ; Chakrabarti, Bhismadev ; Lai, Meng-chuan ; Taylor, Kevin ; Hackett, Gerald ; Bullmore, Edward T. ; Baron-cohen, Simon. / Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans. In: Biological Psychiatry. 2012 ; Vol. 72, No. 10. pp. 839-847.
@article{54ce51033b8f457896d7eaa507a39e60,
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.",
author = "Lombardo, {Michael V.} and Emma Ashwin and Bonnie Auyeung and Bhismadev Chakrabarti and Meng-chuan Lai and Kevin Taylor and Gerald Hackett and Bullmore, {Edward T.} and Simon Baron-cohen",
year = "2012",
month = "11",
day = "15",
doi = "10.1016/j.biopsych.2012.05.027",
language = "English",
volume = "72",
pages = "839--847",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier",
number = "10",

}

TY - JOUR

T1 - Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

AU - Lombardo, Michael V.

AU - Ashwin, Emma

AU - Auyeung, Bonnie

AU - Chakrabarti, Bhismadev

AU - Lai, Meng-chuan

AU - Taylor, Kevin

AU - Hackett, Gerald

AU - Bullmore, Edward T.

AU - Baron-cohen, Simon

PY - 2012/11/15

Y1 - 2012/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84867741450&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1016/j.biopsych.2012.05.027

U2 - 10.1016/j.biopsych.2012.05.027

DO - 10.1016/j.biopsych.2012.05.027

M3 - Article

VL - 72

SP - 839

EP - 847

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 10

ER -