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      Multimodal neuroimaging of male and female brain structure in health and disease across the life span

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          Abstract

          Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

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          Most cited references45

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          Sexual dimorphism of brain developmental trajectories during childhood and adolescence.

          Human total brain size is consistently reported to be approximately 8-10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.
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            Sex differences in the brain: implications for explaining autism.

            Empathizing is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior of nonagentive deterministic systems by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males are stronger systemizers. The "extreme male brain" theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy may also be extremes of typical male neuroanatomy.
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              Age, APOE and sex: Triad of risk of Alzheimer's disease.

              Age, apolipoprotein E ε4 (APOE) and chromosomal sex are well-established risk factors for late-onset Alzheimer's disease (LOAD; AD). Over 60% of persons with AD harbor at least one APOE-ε4 allele. The sex-based prevalence of AD is well documented with over 60% of persons with AD being female. Evidence indicates that the APOE-ε4 risk for AD is greater in women than men, which is particularly evident in heterozygous women carrying one APOE-ε4 allele. Paradoxically, men homozygous for APOE-ε4 are reported to be at greater risk for mild cognitive impairment and AD. Herein, we discuss the complex interplay between the three greatest risk factors for Alzheimer's disease, age, APOE-ε4 genotype and chromosomal sex. We propose that the convergence of these three risk factors, and specifically the bioenergetic aging perimenopause to menopause transition unique to the female, creates a risk profile for AD unique to the female. Further, we discuss the specific risk of the APOE-ε4 positive male which appears to emerge early in the aging process. Evidence for impact of the triad of AD risk factors is most evident in the temporal trajectory of AD progression and burden of pathology in relation to APOE genotype, age and sex. Collectively, the data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer's disease.
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                Author and article information

                Contributors
                neda.jahanshad@usc.edu
                Journal
                J Neurosci Res
                J. Neurosci. Res
                10.1002/(ISSN)1097-4547
                JNR
                Journal of Neuroscience Research
                John Wiley and Sons Inc. (Hoboken )
                0360-4012
                1097-4547
                07 November 2016
                Jan-Feb 2017
                : 95
                : 1-2 , An Issue Whose Time Has Come: Sex/Gender Influences on Nervous System Function ( doiID: 10.1002/jnr.v95.1-2 )
                : 371-379
                Affiliations
                [ 1 ] Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine University of Southern California Marina del Rey California
                Author notes
                [*] [* ]Correspondence to: Neda Jahanshad, PhD, Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292. E‐mail: neda.jahanshad@ 123456usc.edu
                Article
                JNR23919
                10.1002/jnr.23919
                5119539
                27870421
                aa8ea176-20fc-4471-b2a0-99a07e214991
                © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 June 2016
                : 13 August 2016
                : 22 August 2016
                Page count
                Figures: 0, Tables: 0, Pages: 9, Words: 7805
                Categories
                Mini‐Review
                Developmental Neuroscience and Developmental Disorders
                Mini‐Reviews
                Custom metadata
                2.0
                jnr23919
                January/February 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.8 mode:remove_FC converted:25.11.2016

                Neurosciences
                brain development,sexual dimorphism,neuroimaging,magnetic resonance imaging,white matter

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