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Role of testosterone: cortisol ratio in age- and sex-specific cortico-hippocampal development and cognitive performance

Published online by Cambridge University Press:  31 March 2021

Christina Caccese
Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada Research Institute of the McGill University Health Center, Montreal, QC, Canada
Sherri Lee Jones
Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada Research Institute of the McGill University Health Center, Montreal, QC, Canada
Mrinalini Ramesh
Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada
Ally Yu
Department of Psychology, McGill University, Montreal, QC, Canada
Marie Brossard-Racine
Research Institute of the McGill University Health Center, Montreal, QC, Canada School of Physical and Occupational Therapy, Faculty of Medicine, McGill University, Montreal, QC, Canada
Tuong-Vi Nguyen*
Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada Research Institute of the McGill University Health Center, Montreal, QC, Canada Department of Obstetrics-Gynecology, McGill University Health Center, Montreal, QC, Canada
Address for correspondence: Dr. Tuong-Vi Nguyen, McGill University Health Center, Royal Victoria Hospital at the Glen site, 1001 Decarie, Montreal, QC, Canada. Email:


Testosterone (T) and cortisol (C) are steroid hormones that have been argued to play opposing roles in shaping physical and behavioral development in humans. While there is evidence linking T and C to different memory processes during adulthood, it remains unclear how the relative levels of T and C (TC ratio) may influence brain and behavioral development, whether they are influenced by sex of the child, and whether or not they occur as a result of stable changes in brain structure (organizational changes), as opposed to transient changes in brain function (activational changes). As such, we tested for associations among TC ratio, cortico-hippocampal structure, and standardized tests of executive, verbal, and visuo-spatial function in a longitudinal sample of typically developing 4–22-year-old children and adolescents. We found greater TC ratios to be associated with greater coordinated growth (i.e. covariance) between the hippocampus and cortical thickness in several areas primarily devoted to visual function. In addition, there was an age-related association between TC ratio and parieto-hippocampal covariance, as well as a sex-specific association between TC ratio and prefrontal-hippocampal covariance. Differences in brain structure related to TC ratio were in turn associated with lower verbal/executive function, as well as greater attention in tests of visuo-spatial abilities. These results support the notion that TC ratio may shift the balance between top-down (cortex to hippocampus) and bottom-up (hippocampus to cortex) processes, impairing more complex, cortical-based tasks and optimizing visuospatial tasks relying primarily on the hippocampus.

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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Christina Caccese and Sherri Lee Jones contributed equally to the manuscript and share first authorship.


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