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Developmental variation in testosterone:cortisol ratio alters cortical- and amygdala-based cognitive processes

Published online by Cambridge University Press:  29 July 2021

Jimin Lew
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada, H3A2B4 Research Institute of the McGill University Health Center, Montreal, QC, Canada, H4A3J1
Sherri Lee Jones
Research Institute of the McGill University Health Center, Montreal, QC, Canada, H4A3J1 Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A1A1
Christina Caccese
Research Institute of the McGill University Health Center, Montreal, QC, Canada, H4A3J1 Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A1A1
Isobel Orfi
Department of Psychology, McGill University, Montreal, QC, Canada, H4A3J1
Charlotte Little
Department of Psychology, McGill University, Montreal, QC, Canada, H4A3J1
Kelly N. Botteron
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA Brain Development Cooperative Group, USA
James T. McCracken
Brain Development Cooperative Group, USA Department of Child and Adolescent Psychiatry, University of California in Los Angeles, Los Angeles, CA 90024, USA
Tuong-Vi Nguyen*
Research Institute of the McGill University Health Center, Montreal, QC, Canada, H4A3J1 Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A1A1 Department of Obstetrics-Gynecology, McGill University Health Center, Montreal, QC, Canada, H4A3J1
Address for correspondence: Tuong-Vi Nguyen, McGill University Health Center, Royal Victoria Hospital at the Glen Site, 1001 Decarie, Montreal, QC, Canada, H4A3J1. Email:


Testosterone (T) and cortisol (C) are the end products of neuroendocrine axes that interact with the process of shaping brain structure and function. Relative levels of T:C (TC ratio) may alter prefrontal–amygdala functional connectivity in adulthood. What remains unclear is whether TC-related effects are rooted to childhood and adolescence. We used a healthy cohort of 4–22-year-olds to test for associations between TC ratios, brain structure (amygdala volume, cortical thickness (CTh), and their coordinated growth), as well as cognitive and behavioral development. We found greater TC ratios to be associated with the growth of specific brain structures: 1) parietal CTh; 2) covariance of the amygdala with CTh in visual and somatosensory areas. These brain parameters were in turn associated with lower verbal/executive function and higher spatial working memory. In sum, individual TC profiles may confer a particular brain phenotype and set of cognitive strengths and vulnerabilities, prior to adulthood.

Original Article
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Jimin Lew and Sherri Lee Jones contributed equally to the manuscript and share first authorship.


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Developmental variation in testosterone:cortisol ratio alters cortical- and amygdala-based cognitive processes
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