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      A meta-analysis of sex differences in human brain structure

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          Highlights

          • This is the first meta-analysis of sex differences in the typical human brain.

          • Regional sex differences overlap with areas implicated in psychiatric conditions.

          • The amygdala, hippocampus, planum temporale and insula display sex differences.

          • On average, males have larger brain volumes than females.

          • Most articles providing sex differences in volume are in the ‘mature’ category.

          Abstract

          The prevalence, age of onset, and symptomatology of many neuropsychiatric conditions differ between males and females. To understand the causes and consequences of sex differences it is important to establish where they occur in the human brain. We report the first meta-analysis of typical sex differences on global brain volume, a descriptive account of the breakdown of studies of each compartmental volume by six age categories, and whole-brain voxel-wise meta-analyses on brain volume and density. Gaussian-process regression coordinate-based meta-analysis was used to examine sex differences in voxel-based regional volume and density. On average, males have larger total brain volumes than females. Examination of the breakdown of studies providing total volumes by age categories indicated a bias towards the 18–59 year-old category. Regional sex differences in volume and tissue density include the amygdala, hippocampus and insula, areas known to be implicated in sex-biased neuropsychiatric conditions. Together, these results suggest candidate regions for investigating the asymmetric effect that sex has on the developing brain, and for understanding sex-biased neurological and psychiatric conditions.

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          Most cited references152

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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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            Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig.

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              Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder.

              Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference=.408, p<.001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.
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                Author and article information

                Contributors
                Journal
                Neurosci Biobehav Rev
                Neurosci Biobehav Rev
                Neuroscience and Biobehavioral Reviews
                Pergamon Press
                0149-7634
                1873-7528
                1 February 2014
                February 2014
                : 39
                : 100
                : 34-50
                Affiliations
                [a ]Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Road, Cambridge CB2 8AH, United Kingdom
                [b ]Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
                [c ]Department of Psychiatry, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road Section 1, Taipei 10051, Taiwan
                [d ]Cambridgeshire and Peterborough NHS Foundation Trust, Elizabeth House, Fulbourn Hospital, Cambridge CB21 5EF, United Kingdom
                [e ]Department of Psychology, University of Cyprus, P.O. Box 20537, CY 1678 Nicosia, Cyprus
                [f ]Brain Mapping Unit, School of Clinical Medicine, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge CB2 0SP, United Kingdom
                [g ]Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, United Kingdom
                Author notes
                [* ]Corresponding author. Tel.: +44 1223 746030/746057; fax: +44 1223 746033. ar560@ 123456cam.ac.uk
                Article
                S0149-7634(13)00301-1
                10.1016/j.neubiorev.2013.12.004
                3969295
                24374381
                c8bae2e0-ef1e-4568-b175-119e1e1a0bb4
                © 2014 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 June 2013
                : 13 December 2013
                : 17 December 2013
                Categories
                Article

                Neurosciences
                brain,sex differences,meta-analysis,gaussian-process regression (gpr),voxel-based morphometry,volume

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