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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
Affiliation:
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
Affiliation:
Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada Research Institute of the McGill University Health Center, Montreal, QC, Canada
Mrinalini Ramesh
Affiliation:
Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada
Ally Yu
Affiliation:
Department of Psychology, McGill University, Montreal, QC, Canada
Marie Brossard-Racine
Affiliation:
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*
Affiliation:
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: [email protected]

Abstract

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.

Type
Original Article
Copyright
© 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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Footnotes

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

References

Liening, SH, Stanton, SJ, Saini, EK, Schultheiss, OC. Salivary testosterone, cortisol, and progesterone: two-week stability, interhormone correlations, and effects of time of day, menstrual cycle, and oral contraceptive use on steroid hormone levels. Physiol Behav. 2010; 99(1), 816.CrossRefGoogle ScholarPubMed
Kapoor, A, Matthews, SG. Testosterone is involved in mediating the effects of prenatal stress in male guinea pig offspring. J Physiol. 2011; 589(Pt 3), 755766.CrossRefGoogle ScholarPubMed
Montoya, ER, Terburg, D, Bos, PA, van Honk, J. Testosterone, cortisol, and serotonin as key regulators of social aggression: a review and theoretical perspective. Motiv Emot. 2012; 36(1), 6573.CrossRefGoogle ScholarPubMed
Gaffey, AE, Martinez, BS. Neuroendocrine Mechanisms of Psychological Stress: Age and Sex Differences in Adults, 2019. Oxford University Press, Oxford, UK.Google Scholar
Maeng, LY, Milad, MR. Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav. 2015; 76, 106117.CrossRefGoogle ScholarPubMed
Nguyen, TV, Jones, SL, Elgbeili, G, et al. Testosterone-cortisol dissociation in children exposed to prenatal maternal stress, and relationship with aggression: project ice storm. Dev Psychopathol. 2018; 30(3), 981994.CrossRefGoogle ScholarPubMed
Tabori, NE, Stewart, LS, Znamensky, V, et al. Ultrastructural evidence that androgen receptors are located at extranuclear sites in the rat hippocampal formation. Neuroscience. 2005; 130(1), 151163.CrossRefGoogle ScholarPubMed
Kalafatakis, K, Giannakeas, N, Lightman, SL, et al. Utilization of the allen gene expression atlas to gain further insight into glucocorticoid physiology in the adult mouse brain. Neurosci Lett. 2019; 706, 194200.CrossRefGoogle ScholarPubMed
Neufang, S, Specht, K, Hausmann, M, et al. Sex differences and the impact of steroid hormones on the developing human brain. Cereb Cortex. 2009; 19(2), 464473.CrossRefGoogle ScholarPubMed
McAuley, MT, Kenny, RA, Kirkwood, TB, Wilkinson, DJ, Jones, JJ, Miller, VM. A mathematical model of aging-related and cortisol induced hippocampal dysfunction. BMC Neurosci. 2009; 10, 26.CrossRefGoogle ScholarPubMed
Panizzon, MS, Hauger, RL, Xian, H, et al. Interactive effects of testosterone and cortisol on hippocampal volume and episodic memory in middle-aged men. Psychoneuroendocrinol. 2018; 91, 115122.CrossRefGoogle ScholarPubMed
Nguyen, TV, Lew, J, Albaugh, MD, et al. Sex-specific associations of testosterone with prefrontal-hippocampal development and executive function. Psychoneuroendocrinol. 2017; 76, 206217.CrossRefGoogle ScholarPubMed
Nguyen, TV, McCracken, J, Ducharme, S, et al. Testosterone-related cortical maturation across childhood and adolescence. Cereb Cortex. 2013; 23(6), 14241432.CrossRefGoogle ScholarPubMed
Alexander-Bloch, A, Giedd, JN, Bullmore, E. Imaging structural co-variance between human brain regions. Nat Rev Neurosci. 2013; 14(5), 322336.CrossRefGoogle ScholarPubMed
Farooqi, NAI, Scotti, M, Yu, A, et al. Sex-specific contribution of DHEA-Cortisol ratio to prefrontal-hippocampal structural development, cognitive abilities and personality traits. J Neuroendocrinol. 2018; e12682. doi: 10.1111/jne.12682.Google Scholar
Platje, E, Popma, A, Vermeiren, RR, et al. Testosterone and cortisol in relation to aggression in a non-clinical sample of boys and girls. Aggress Behav. 2015; 41(5), 478487.CrossRefGoogle Scholar
Barel, E, Shahrabani, S, Tzischinsky, O. Sex hormone/cortisol ratios differentially modulate risk-taking in men and women. Evol Psychol. 2017; 15(1), 1474704917697333.CrossRefGoogle ScholarPubMed
Mehta, PH, Josephs, RA. Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone hypothesis. Horm Behav. 2010; 58(5), 898906.CrossRefGoogle ScholarPubMed
Evans, AC. The NIH MRI study of normal brain development. Neuroimage. 2006; 30(1), 184202.CrossRefGoogle ScholarPubMed
Khan-Dawood, FS, Choe, JK, Dawood, MY. Salivary and plasma bound and “free” testosterone in men and women. Am J Obstet Gynecol. 1984; 148(4), 441445.CrossRefGoogle ScholarPubMed
Kancheva, R, Hill, M, Novák, Z, et al. Peripheral neuroactive steroids may be as good as the steroids in the cerebrospinal fluid for the diagnostics of CNS disturbances. J Steroid Biochem Mol Biol. 2010; 119(1), 3544.CrossRefGoogle ScholarPubMed
Francavilla, VC, Vitale, F, Ciaccio, M, et al. Use of Saliva in alternative to serum sampling to monitor biomarkers modifications in professional soccer players. Front Physiol. 2018; 9, 1828.CrossRefGoogle ScholarPubMed
Brambilla, DJ, Matsumoto, AM, Araujo, AB, McKinlay, JB. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab 2009; 94(3), 907913.CrossRefGoogle ScholarPubMed
Parikh, TP, Stolze, BR, Ozarda Ilcol, Y, et al. Diurnal variation of steroid hormones and reference intervals using mass spectrometric analysis. Endocr Connect. 2018. doi: 10.1530/EC-18-0417.CrossRefGoogle ScholarPubMed
Ankarberg, C, Norjavaara, E. Diurnal rhythm of testosterone secretion before and throughout puberty in healthy girls: correlation with 17beta-estradiol and dehydroepiandrosterone sulfate. J Clin Endocrinol Metab 1999; 84(3), 975984.Google ScholarPubMed
Bae, YJ, Zeidler, R, Baber, R, et al. Reference intervals of nine steroid hormones over the life-span analyzed by LC-MS/MS: effect of age, gender, puberty, and oral contraceptives. J Steroid Biochem Mol Biol. 2019; 193, 105409.CrossRefGoogle ScholarPubMed
Raven, G, de Jong, FH, Kaufman, J-M, In Men, de Ronde W., Peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion. J Clin Endocrinol Metab. 2006; 91(9), 33243328.CrossRefGoogle ScholarPubMed
Petersen, A, Crockett, L, Richards, M, Boxer, A. A self-report measure of pubertal status: reliability, validity, and initial norms. J Youth Adolesc. 1988; 17(2), 117133.CrossRefGoogle ScholarPubMed
Khoury, JE, Gonzalez, A, Levitan, RD, et al. Summary cortisol reactivity indicators: interrelations and meaning. Neurobiol Stress. 2015; 2, 3443.CrossRefGoogle ScholarPubMed
Fekedulegn, DB, Andrew, ME, Burchfiel, CM, et al. Area under the curve and other summary indicators of repeated waking cortisol measurements. Psychosom Med. 2007; 69(7), 651659.CrossRefGoogle ScholarPubMed
Nguyen, TV, McCracken, JT, Ducharme, S, et al. Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development. J Neurosci. 2013; 33(26), 1084010848.CrossRefGoogle ScholarPubMed
Lyttelton, O, Boucher, M, Robbins, S, Evans, A. An unbiased iterative group registration template for cortical surface analysis. Neuroimage. 2007; 34(4), 15351544.CrossRefGoogle ScholarPubMed
Sled, JG, Zijdenbos, AP, Evans, AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 1998; 17(1), 8797.CrossRefGoogle ScholarPubMed
Zijdenbos, AP, Forghani, R, Evans, AC. Automatic “pipeline” analysis of 3-D MRI data for clinical trials: application to multiple sclerosis. IEEE Trans Med Imaging 2002; 21(10), 12801291.CrossRefGoogle ScholarPubMed
Collins, DL, Pruessner, JC. Towards accurate, automatic segmentation of the hippocampus and amygdala from MRI by augmenting ANIMAL with a template library and label fusion. Neuroimage. 2010; 52(4), 13551366.CrossRefGoogle ScholarPubMed
Pruessner, JC, Collins, DL, Pruessner, M, Evans, AC. Age and gender predict volume decline in the anterior and posterior hippocampus in early adulthood. J Neurosci. 2001; 21(1), 194200.CrossRefGoogle ScholarPubMed
Pruessner, JC, Li, LM, Serles, W, et al. Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex. 2000; 10(4), 433442.CrossRefGoogle ScholarPubMed
Collins, DL, Evans, AC. Animal: validation and applications of nonlinear registration-based segmentation. Int J Pattern Recognit Artif Intell 1997; 11(08), 12711294.CrossRefGoogle Scholar
Strauss, E, Sherman, EMS, Spreen, O, Spreen, O. A Compendium of Neuropsychological Tests : Administration, Norms, and Commentary, 3rd edn, 2006. Oxford University Press, Oxford; New York.Google Scholar
Luciana, M. Practitioner review: computerized assessment of neuropsychological function in children: clinical and research applications of the Cambridge Neuropsychological Testing Automated Battery (CANTAB). J Child Psychol Psychiatry. 2003; 44(5), 649663.CrossRefGoogle Scholar
Worsley, KJ, Evans, AC, Marrett, S, Neelin, P. A three-dimensional statistical analysis for CBF activation studies in human brain. J. Cereb Blood Flow Metab. 1992; 12(6), 900918.CrossRefGoogle Scholar
Hamson, DK, Roes, MM, Galea, LA. Sex hormones and cognition: neuroendocrine influences on memory and learning. Compr Physiol. 2016; 6(3), 12951337.CrossRefGoogle ScholarPubMed
Farooqi, NAI, Scotti, M, Lew, JM, et al. Role of DHEA and cortisol in prefrontal-amygdalar development and working memory. Psychoneuroendocrinol. 2018; 98, 8694.CrossRefGoogle ScholarPubMed
Butler, K, Klaus, K, Edwards, L, Pennington, K. Elevated cortisol awakening response associated with early life stress and impaired executive function in healthy adult males. Horm Behav. 2017; 95, 1321.CrossRefGoogle ScholarPubMed
Ostatnikova, D, Celec, P, Putz, Z, et al. Intelligence and salivary testosterone levels in prepubertal children. Neuropsychologia. 2007; 45(7), 13781385.CrossRefGoogle ScholarPubMed
Xing, X, Yin, T, Wang, M. Cortisol stress reactivity moderates the effects of parental corporal punishment on Chinese preschoolers’ executive function. Child Abuse Negl. 2019; 88, 288297.CrossRefGoogle ScholarPubMed
Salmon, E, Van der Linden, M, Collette, F, et al. Regional brain activity during working memory tasks. Brain 1996; 119 (Pt 5), 16171625.CrossRefGoogle ScholarPubMed
Pham, AV, Hasson, RM. Verbal and visuospatial working memory as predictors of children’s reading ability. Arch Clin Neuropsychol 2014; 29(5), 467477.CrossRefGoogle ScholarPubMed
Kintsch, W, Patel, VL, Ericsson, KA. The role of long-term working memory in text comprehension. Psychologia: Int J Psychol Orient. 1999; 42(4), 186198.Google Scholar
Mattson, MP. Superior pattern processing is the essence of the evolved human brain. Front Neurosci. 2014; 8, 265.CrossRefGoogle ScholarPubMed
Handa, R, McGivern, R. Steroid hormones, receptors, and perceptual and cognitive sex differences in the visual system. Curr Eye Res. 2014; 40, 118.Google ScholarPubMed
Foradori, CD, Weiser, MJ, Handa, RJ. Non-genomic actions of androgens. Front Neuroendocrinol. 2008; 29(2), 169181.CrossRefGoogle ScholarPubMed
Green, MR, Nottrodt, RE, Simone, JJ, McCormick, CM. Glucocorticoid receptor translocation and expression of relevant genes in the hippocampus of adolescent and adult male rats. Psychoneuroendocrinol. 2016; 73, 3241.CrossRefGoogle ScholarPubMed
Nguyen, TV, Jones, SL, Gower, T, et al. Age-specific associations between oestradiol, cortico-amygdalar structural covariance, and verbal and spatial skills. J Neuroendocrinol. 2019; 31(4), e12698.CrossRefGoogle ScholarPubMed
Labrie, F, Luu-The, V, Labrie, C, Simard, J. DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology. Front Neuroendocrinol. 2001; 22(3), 185212.CrossRefGoogle ScholarPubMed
Seeman, TE, Singer, B, Wilkinson, CW, Bruce, M. Gender differences in age-related changes in HPA axis reactivity. Psychoneuroendocrinology. 2001; 26(3), 225240.CrossRefGoogle ScholarPubMed
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