Investigating Sexual Dimorphism of Human White Matter in a Harmonized, Multisite Diffusion Magnetic Resonance Imaging Study

Johanna Seitz; Suheyla Cetin-Karayumak; Amanda Lyall; Ofer Pasternak; Madhura Baxi; Mark Vangel; Godfrey Pearlson; Carol Tamminga; John Sweeney; Brett Clementz; David Schretlen; Petra Verena Viher; Katharina Stegmayer; Sebastian Walther; Jungsun Lee; Tim Crow; Anthony James; Aristotle Voineskos; Robert W Buchanan; Philip R Szeszko; Anil Malhotra; Matcheri Keshavan; Inga K Koerte; Martha E Shenton; Yogesh Rathi; Marek Kubicki

doi:10.1093/cercor/bhaa220

Investigating Sexual Dimorphism of Human White Matter in a Harmonized, Multisite Diffusion Magnetic Resonance Imaging Study

Cereb Cortex. 2021 Jan 1;31(1):201-212. doi: 10.1093/cercor/bhaa220.

Authors

Johanna Seitz¹, Suheyla Cetin-Karayumak¹, Amanda Lyall^{1

2}, Ofer Pasternak^{1

2

3}, Madhura Baxi^{1

4}, Mark Vangel⁵, Godfrey Pearlson⁶, Carol Tamminga⁷, John Sweeney⁸, Brett Clementz⁹, David Schretlen¹⁰, Petra Verena Viher¹¹, Katharina Stegmayer¹¹, Sebastian Walther¹¹, Jungsun Lee¹², Tim Crow¹³, Anthony James¹³, Aristotle Voineskos¹⁴, Robert W Buchanan¹⁵, Philip R Szeszko^{16

17}, Anil Malhotra¹⁸, Matcheri Keshavan¹⁹, Inga K Koerte^{1

20}, Martha E Shenton^{1

2

3

21}, Yogesh Rathi^{1

2

3}, Marek Kubicki^{1

2

3}

Affiliations

¹ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, 02115, USA.
² Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, MA, Boston, 02114, USA.
³ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, 02115, USA.
⁴ Graduate Program of Neuroscience, Boston University, Boston, MA, 02215, USA.
⁵ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, 02115, USA.
⁶ Department of Psychiatry, Yale University, New Haven, CT, 06520, USA.
⁷ Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
⁸ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, 45221, USA.
⁹ Department of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, 30601, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, 21205, USA.
¹¹ University of Bern, University Hospital of Psychiatry, Bern, 3012, Switzerland.
¹² Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 690-749, Korea.
¹³ Department of Psychiatry, SANE POWIC, Warneford Hospital, University of Oxford, Oxford, OX3 7 JX, UK.
¹⁴ Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, M5T1R8, Canada.
¹⁵ Maryland Psychiatry Research Center, University of Maryland School of Medicine, Baltimore, 21228, USA.
¹⁶ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
¹⁷ Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center, Bronx, New York, 10461, USA.
¹⁸ The Feinstein Institute for Medical Research and Zucker Hillside Hospital, Manhasset, 11030, USA.
¹⁹ Department of Psychiatry, Beth Israel Deaconess Medical Centre, Harvard Medical School, MA, Boston, 02115, USA.
²⁰ cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-Universität, Munich, 80337, Germany.
²¹ VA Boston Healthcare System, Brockton, MA, 02301, USA.

Abstract

Axonal myelination and repair, critical processes for brain development, maturation, and aging, remain controlled by sexual hormones. Whether this influence is reflected in structural brain differences between sexes, and whether it can be quantified by neuroimaging, remains controversial. Diffusion-weighted magnetic resonance imaging (dMRI) is an in vivo method that can track myelination changes throughout the lifespan. We utilize a large, multisite sample of harmonized dMRI data (n = 551, age = 9-65 years, 46% females/54% males) to investigate the influence of sex on white matter (WM) structure. We model lifespan trajectories of WM using the most common dMRI measure fractional anisotropy (FA). Next, we examine the influence of both age and sex on FA variability. We estimate the overlap between male and female FA and test whether it is possible to label individual brains as male or female. Our results demonstrate regionally and spatially specific effects of sex. Sex differences are limited to limbic structures and young ages. Additionally, not only do sex differences diminish with age, but tracts within each subject become more similar to one another. Last, we show the high overlap in FA between sexes, which implies that determining sex based on WM remains open.

Keywords: connectivity; diffusion-weighted MRI; female; fractional anisotropy; male.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aged
Aging
Anisotropy
Axons / physiology
Child
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
Female
Humans
Limbic System / diagnostic imaging
Limbic System / physiology
Male
Middle Aged
Myelin Sheath / physiology
Neural Pathways / diagnostic imaging
Neural Pathways / physiology
Sex Characteristics*
White Matter / anatomy & histology*
White Matter / diagnostic imaging*
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding