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Associations between testosterone, estradiol, and androgen receptor genotype with amygdala subregions in adolescents

Campbell, Claire E. and Mezher, Adam F. and Tyszka, J. Michael and Nagel, Bonnie J. and Eckel, Sandrah P. and Herting, Megan M. (2022) Associations between testosterone, estradiol, and androgen receptor genotype with amygdala subregions in adolescents. Psychoneuroendocrinology, 137 . Art. No. 105604. ISSN 0306-4530. PMCID PMC8925279. doi:10.1016/j.psyneuen.2021.105604.

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Much is known about the development of the whole amygdala, but less is known about its structurally and functionally diverse subregions. One notable distinguishing feature is their wide range of androgen and estrogen receptor densities. Given the rise in pubertal hormones during adolescence, sex steroid levels as well as receptor sensitivity could influence age-related subregion volumes. Therefore, our goal was to evaluate the associations between the total amygdala and its subregion volumes in relation to sex hormones – estradiol and free testosterone (FT) – as a function of age and genetic differences in androgen receptor (AR) sensitivity in a sample of 297 adolescents (46% female). In males, we found small effects of FT-by-age interactions in the total amygdala, portions of the basolateral complex, and the cortical and medial nuclei (CMN), with the CMN effects being moderated by AR sensitivity. For females, small effects were seen with increased genetic AR sensitivity relating to smaller basolateral complexes. However, none of these small effects passed multiple comparisons. Future larger studies are necessary to replicate these small, yet possibly meaningful effects of FT-by-age associations and modulation by AR sensitivity on amygdala development to ultimately determine if they contribute to known sex differences in emotional neurodevelopment.

Item Type:Article
Related URLs:
URLURL TypeDescription
Campbell, Claire E.0000-0001-5288-9479
Mezher, Adam F.0000-0002-9317-1137
Tyszka, J. Michael0000-0001-9342-9014
Nagel, Bonnie J.0000-0001-6339-7453
Eckel, Sandrah P.0000-0001-6050-7880
Herting, Megan M.0000-0002-0840-4582
Additional Information:© 2021 Elsevier Ltd. Received 13 May 2021, Revised 18 November 2021, Accepted 19 November 2021, Available online 24 November 2021. The research above was supported by the following grants, T32 ES013678 (Campbell); R01 AA017664 (PI: Nagel), R21 MH099618 (PI: Nagel), R03 HD090308 (PI: Herting), K01 MH108761 (PI: Herting), and NIMH P50 MH094258 (PI: Adolphs). We also thank the families who contributed their time and participated in the above study. The authors have no conflicts of interest to disclose.
Funding AgencyGrant Number
NIH Predoctoral FellowshipT32 ES013678
NIHR01 AA017664
NIHR21 MH099618
NIHR03 HD090308
NIHK01 MH108761
NIHP50 MH094258
Subject Keywords:Amygdala; Androgen receptor; Adolescence; Lateral amygdala; Testosterone; Estradiol
PubMed Central ID:PMC8925279
Record Number:CaltechAUTHORS:20211202-191325714
Persistent URL:
Official Citation:Claire E. Campbell, Adam F. Mezher, J. Michael Tyszka, Bonnie J. Nagel, Sandrah P. Eckel, Megan M. Herting, Associations between testosterone, estradiol, and androgen receptor genotype with amygdala subregions in adolescents, Psychoneuroendocrinology, Volume 137, 2022, 105604, ISSN 0306-4530,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:112167
Deposited By: George Porter
Deposited On:03 Dec 2021 15:40
Last Modified:06 Apr 2022 20:33

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