{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:43:03Z","timestamp":1784004183336,"version":"3.55.0"},"reference-count":129,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006475","name":"Bergen Research Foundation","doi-asserted-by":"publisher","award":["BFS2017TMT01"],"award-info":[{"award-number":["BFS2017TMT01"]}],"id":[{"id":"10.13039\/501100006475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The societal implication of sex and gender (SG) differences in brain are profound, as they influence brain development, behavior, and importantly, the presentation, prevalence, and therapeutic response to diseases. Technological advances have enabled speed up identification and characterization of SG differences during development and in psychopathologies. The main aim of this review is to elaborate on new technological advancements, such as genomics, imaging, and emerging biobanks, coupled with bioinformatics analyses of data generated from these technologies have facilitated the identification and characterization of SG differences in the human brain through development and psychopathologies. First, a brief explanation of SG concepts is provided, along with a developmental and evolutionary context. We then describe physiological SG differences in brain activity and function, and in psychopathologies identified through imaging techniques. We further provide an overview of insights into SG differences using genomics, specifically taking advantage of large cohorts and biobanks. We finally emphasize how bioinformatics analyses of big data generated by emerging technologies provides new opportunities to reduce SG disparities in health outcomes, including major challenges.<\/jats:p>","DOI":"10.3390\/life13081676","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:57:33Z","timestamp":1690973853000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Insights into Sex and Gender Differences in Brain and Psychopathologies Using Big Data"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-6355","authenticated-orcid":false,"given":"Aura","family":"Zelco","sequence":"first","affiliation":[{"name":"Department of Clinical Science, Computational Biology Unit, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattama","family":"Wapeesittipan","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Computational Biology Unit, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anagha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Computational Biology Unit, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","unstructured":"Harkin, T., Snowe, O.J., Mikulski, B.A., and Waxman, H.A. (2001). Drug Safety: Most Drugs Withdrawn in Recent Years Had Greater Health Risks for Women."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrendo.2014.130","article-title":"DSDs: Genetics, underlying pathologies and psychosexual differentiation","volume":"10","author":"Arboleda","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/ajmg.a.34123","article-title":"High-level 46XX\/46XY chimerism without clinical effect in a healthy multiparous female","volume":"155","author":"James","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chan, W.F.N., Gurnot, C., Montine, T.J., Sonnen, J.A., Guthrie, K.A., and Nelson, J.L. (2012). Male Microchimerism in the Human Female Brain. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045592"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s11199-011-9932-5","article-title":"Distinguishing Between Sex and Gender: History, Current Conceptualizations, and Implications","volume":"64","author":"Muehlenhard","year":"2011","journal-title":"Sex Roles"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ecl.2019.01.002","article-title":"Etiology of Gender Identity","volume":"48","author":"Korpaisarn","year":"2019","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1124\/jpet.120.266163","article-title":"Neuroimmune Mechanisms and Sex\/Gender-Dependent Effects in the Pathophysiology of Mental Disorders","volume":"375","author":"Kokkosis","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s10508-015-0490-8","article-title":"Beyond Sexual Orientation: Integrating Gender\/Sex and Diverse Sexualities via Sexual Configurations Theory","volume":"44","year":"2015","journal-title":"Arch. Sex. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0140","DOI":"10.2106\/JBJS.RVW.19.00140","article-title":"The Biology of Sex and Sport","volume":"8","author":"Bassett","year":"2020","journal-title":"JBJS Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Trofimova, I. (2011). Are men evolutionarily wired to love the \u201cEasy\u201d buttons?. Nat. Preced.","DOI":"10.1038\/npre.2011.5562.1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1080\/03081079.2015.1032529","article-title":"The evolutionary theory of asymmetry by V. Geodakyan","volume":"44","author":"Geodakyan","year":"2015","journal-title":"Int. J. Gen. Syst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/BF02365058","article-title":"The role of sex chromosomes in evolution: A new concept","volume":"93","author":"Geodakian","year":"1999","journal-title":"J. Math. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrg1985","article-title":"The evolution of sex: Empirical insights into the roles of epistasis and drift","volume":"8","author":"Elena","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/evan.21834","article-title":"Expanding the evolutionary explanations for sex differences in the human skeleton","volume":"29","author":"Dunsworth","year":"2020","journal-title":"Evol. Anthropol. Issues News Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1037\/0003-066X.60.6.581","article-title":"The gender similarities hypothesis","volume":"60","author":"Hyde","year":"2005","journal-title":"Am. Psychol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104691","DOI":"10.1016\/j.yhbeh.2020.104691","article-title":"Sexual differentiation of brain and other tissues: Five questions for the next 50 years","volume":"120","author":"Arnold","year":"2020","journal-title":"Horm. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/jnr.24945","article-title":"Genetics, sex, and gender","volume":"101","author":"Reale","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng1705","article-title":"Dosage compensation of the active X chromosome in mammals","volume":"38","author":"Nguyen","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrg.2017.36","article-title":"Human Y-chromosome variation in the genome-sequencing era","volume":"18","author":"Jobling","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mce.2006.12.029","article-title":"Genetic programs that regulate testicular and ovarian development","volume":"265\u2013266","author":"Cederroth","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_21","first-page":"27","article-title":"Meningiomas: Histogenesis and classification. A comparative morphological study","volume":"134","author":"Mennel","year":"1988","journal-title":"Zentralbl. Allg. Pathol. Pathol. Anat."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"McGivern, R.F., Mosso, M., Freudenberg, A., and Handa, R.J. (2019). Sex related biases for attending to object color versus object position are reflected in reaction time and accuracy. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210272"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105444","DOI":"10.1016\/j.cmpb.2020.105444","article-title":"Gender-based functional connectivity differences in brain networks in childhood","volume":"192","author":"Acer","year":"2020","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1136\/postgradmedj-2019-137452","article-title":"Gender medicine: Its historical roots","volume":"96","author":"Lippi","year":"2020","journal-title":"Postgrad. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/B978-0-12-820683-6.00031-2","article-title":"Sexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation","volume":"181","author":"Swaab","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1523\/JNEUROSCI.0750-19.2019","article-title":"Neuroscience and Sex\/Gender: Looking Back and Forward","volume":"40","author":"Hines","year":"2020","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/7854_2018_56","article-title":"Sexual Differentiation and Sex Differences in Neural Development","volume":"43","author":"Turano","year":"2019","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1210\/en.2003-1504","article-title":"Minireview: Sex differences in adult and developing brains: Compensation, compensation, compensation","volume":"145","year":"2004","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ristori, J., Cocchetti, C., Romani, A., Mazzoli, F., Vignozzi, L., Maggi, M., and Fisher, A.D. (2020). Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062123"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neurobiolaging.2021.06.002","article-title":"Age- and gender-related differences in brain tissue microstructure revealed by multi-component T2 relaxometry","volume":"106","author":"Verdolini","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/17588928.2020.1800617","article-title":"Development of sex differences in the human brain","volume":"12","author":"Kurth","year":"2021","journal-title":"Cogn. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13293-019-0245-7","article-title":"Sex differences in gray matter volume: How many and how large are they really?","volume":"10","author":"Aguirre","year":"2019","journal-title":"Biol. Sex Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-444-64123-6.00001-1","article-title":"Structural differences between male and female brains","volume":"175","author":"Luders","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.neubiorev.2021.02.026","article-title":"Dump the \u201cdimorphism\u201d: Comprehensive synthesis of human brain studies reveals few male-female differences beyond size","volume":"125","author":"Eliot","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1177\/0271678X16668536","article-title":"Sex differences of human cortical blood flow and energy metabolism","volume":"37","author":"Aanerud","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/17588928.2020.1806810","article-title":"Are there sex differences in brain activity during long-term memory? A systematic review and fMRI activation likelihood estimation meta-analysis","volume":"12","author":"Spets","year":"2021","journal-title":"Cogn. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1002\/hbm.23659","article-title":"Network for Efficiency and Standardization of Dementia Diagnosis (NEST-DD) database. Gender differences in healthy aging and Alzheimer\u2019s Dementia: A 18 F-FDG-PET study of brain and cognitive reserve","volume":"38","author":"Malpetti","year":"2017","journal-title":"Hum. Brain Mapp."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1111\/ejn.15107","article-title":"Sex differences in executive control: A systematic review of functional neuroimaging studies","volume":"53","author":"Gaillard","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e201700120","DOI":"10.1002\/jbio.201700120","article-title":"Gender differences in brain networks during verbal Sternberg tasks: A simultaneous near-infrared spectroscopy and electro-encephalography study","volume":"11","author":"Gao","year":"2018","journal-title":"J. Biophotonics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117507","DOI":"10.1016\/j.neuroimage.2020.117507","article-title":"Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory: An fMRI study","volume":"225","author":"Charron","year":"2021","journal-title":"NeuroImage"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/B978-0-444-64123-6.00007-2","article-title":"Gender differences in language are small but matter for disorders","volume":"175","author":"Wallentin","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1017\/S1138741600005801","article-title":"Null sex differences in general intelligence: Evidence from the WAIS-III","volume":"5","author":"Colom","year":"2002","journal-title":"Span. J. Psychol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1093\/cercor\/bhz134","article-title":"Gender Differences in Connectome-based Predictions of Individualized Intelligence Quotient and Sub-domain Scores","volume":"30","author":"Jiang","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2989\/17280583.2020.1848850","article-title":"Gender differences in brain type according to the Empathy\/Systemising Quotient for Children (EQ\/SQ-C) questionnaire in Indonesia","volume":"32","author":"Chaidir","year":"2020","journal-title":"J. Child Adolesc. Ment. Health"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dhingra, I., Zhang, S., Zhornitsky, S., Wang, W., Le, T.M., and Li, C.S.R. (2021). Sex differences in neural responses to reward and the influences of individual reward and punishment sensitivity. BMC Neurosci., 22.","DOI":"10.1186\/s12868-021-00618-3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/hbm.24388","article-title":"Sex differences in own and other body perception","volume":"40","author":"Burke","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.jalz.2019.04.006","article-title":"Sex\/gender differences in cognitive trajectories vary as a function of race\/ethnicity","volume":"15","author":"Avila","year":"2019","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/jnr.24970","article-title":"Sex and gender difference in cognitive and behavioral studies in developmental age: An introduction","volume":"101","author":"Riva","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1080\/1357650X.2018.1497044","article-title":"Cognitive sex differences and hemispheric asymmetry: A critical review of 40 years of research","volume":"24","author":"Hirnstein","year":"2019","journal-title":"Laterality"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1002\/hbm.24462","article-title":"Machine learning of brain gray matter differentiates sex in a large forensic sample","volume":"40","author":"Anderson","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"ref_51","first-page":"3698","article-title":"Correlations Between Personality and Brain Structure: A Crucial Role of Gender","volume":"27","author":"Nostro","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E191","DOI":"10.36076\/ppj\/2019.22.E191","article-title":"Gender Differences in the Association of Brain Gray Matter and Pain-Related Psychosocial Characteristics","volume":"22","author":"Malfliet","year":"2019","journal-title":"Pain Physician"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.neuroimage.2018.10.013","article-title":"Sex difference in brain CB1 receptor availability in man","volume":"184","author":"Laurikainen","year":"2019","journal-title":"NeuroImage"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.neubiorev.2021.09.012","article-title":"Sex\/gender differences in the brain are not trivial\u2014A commentary on Eliot et al. (2021)","volume":"130","author":"Hirnstein","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2857","DOI":"10.1002\/brb3.2857","article-title":"Are sex differences in self-estimated intelligence an elusive phenomenon? Exploring the role of working memory, creativity, and other psychological correlates in young and older adults","volume":"13","author":"Giannouli","year":"2023","journal-title":"Brain Behav."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/17588928.2020.1853087","article-title":"Sex\/gender differences in brain activity\u2014It\u2019s time for a biopsychosocial approach to cognitive neuroscience","volume":"12","author":"Hausmann","year":"2021","journal-title":"Cogn. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"485","DOI":"10.5406\/amerjpsyc.128.4.0485","article-title":"Do Psychological Sex Differences Reflect Evolutionary Bisexual Partitioning?","volume":"128","author":"Trofimova","year":"2015","journal-title":"Am. J. Psychol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hartung, C., and Lefler, E. (2019). Sex and gender in psychopathology: DSM-5 and beyond. Psychol. Bull.","DOI":"10.1037\/bul0000183"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1177\/1745691616650677","article-title":"Evolution of Sex Differences in Trait- and Age-Specific Vulnerabilities","volume":"11","author":"Geary","year":"2016","journal-title":"Perspect. Psychol. Sci. J. Assoc. Psychol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.jaac.2018.09.425","article-title":"Beyond a Binary Classification of Sex: An Examination of Brain Sex Differentiation, Psychopathology, and Genotype","volume":"58","author":"Phillips","year":"2019","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.biopsych.2021.02.972","article-title":"Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders","volume":"91","author":"Blokland","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S2215-0366(16)30263-2","article-title":"Why is depression more common among women than among men?","volume":"4","author":"Kuehner","year":"2017","journal-title":"Lancet. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"650904","DOI":"10.3389\/fpsyt.2021.650904","article-title":"The Pharmacodynamics of Antipsychotic Drugs in Women and Men","volume":"12","author":"Seeman","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Arora, P., Gudelsky, G., and Desai, P.B. (2021). Gender-based differences in brain and plasma pharmacokinetics of letrozole in sprague-dawley rats: Application of physiologically-based pharmacokinetic modeling to gain quantitative insights. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248579"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"(2022). Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry, 9, 137\u2013150.","DOI":"10.1016\/S2215-0366(21)00395-3"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/nm.4386","article-title":"Sex-specific transcriptional signatures in human depression","volume":"23","author":"Engmann","year":"2017","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Dumont, L., Marin, M.F., Lupien, S.J., and Juster, R.P. (2020). Sex Differences in Work-Stress Memory Bias and Stress Hormones. Brain Sci., 10.","DOI":"10.3390\/brainsci10070432"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107829","DOI":"10.1016\/j.neuropsychologia.2021.107829","article-title":"Gender differences in functional connectivity during emotion regulation","volume":"156","author":"Stoica","year":"2021","journal-title":"Neuropsychologia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/17588928.2020.1793752","article-title":"Sex-related differences in brain dynamism at rest as neural correlates of positive and negative valence system constructs","volume":"12","author":"Kutz","year":"2021","journal-title":"Cogn. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"134776","DOI":"10.1016\/j.neulet.2020.134776","article-title":"Androgyny eliminates sex differences in emotional reactivity: ERP and network coupling evidences","volume":"720","author":"Yu","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s12264-020-00588-2","article-title":"Gender Role, But Not Sex, Shapes Humans\u2019 Susceptibility to Emotion","volume":"37","author":"Yuan","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1093\/cercor\/bhz170","article-title":"Sex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging","volume":"30","author":"Seiger","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00787-018-1169-1","article-title":"Childhood aggression and the co-occurrence of behavioural and emotional problems: Results across ages 3\u201316 years from multiple raters in six cohorts in the EU-ACTION project","volume":"27","author":"Bartels","year":"2018","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.neulet.2017.12.006","article-title":"Gender differences in anomalous subcortical morphology for children with ADHD","volume":"665","author":"Wang","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.biopsych.2021.04.016","article-title":"Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder","volume":"91","author":"Hitzemann","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e41723","DOI":"10.7554\/eLife.41723","article-title":"Alcoholism gender differences in brain responsivity to emotional stimuli","volume":"8","author":"Sawyer","year":"2019","journal-title":"eLife"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.expneurol.2019.02.016","article-title":"Sex differences in pediatric traumatic brain injury","volume":"317","author":"Arambula","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41593-020-00748-7","article-title":"Transcriptomic organization of the human brain in post-traumatic stress disorder","volume":"24","author":"Girgenti","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_79","first-page":"320","article-title":"Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder","volume":"5","author":"Lee","year":"2020","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/aur.2506","article-title":"Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study","volume":"14","author":"Deng","year":"2021","journal-title":"Autism Res. Off. J. Int. Soc. Autism Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13229-016-0073-0","article-title":"An investigation of the \u2019female camouflage effect\u2019 in autism using a computerized ADOS-2 and a test of sex\/gender differences","volume":"7","author":"Rynkiewicz","year":"2016","journal-title":"Mol. Autism"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13229-018-0216-6","article-title":"Self-reported sex differences in high-functioning adults with autism: A meta-analysis","volume":"9","author":"Moseley","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/B978-0-444-64123-6.00016-3","article-title":"Brain structural and neuroendocrine basis of sex differences in epilepsy","volume":"175","author":"Reddy","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"135753","DOI":"10.1016\/j.neulet.2021.135753","article-title":"Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis","volume":"750","author":"Reddy","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neubiorev.2019.04.003","article-title":"Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders","volume":"102","author":"Ullah","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"10634","DOI":"10.1073\/pnas.1904673116","article-title":"Reply to Biskup et al. and Tu et al.: Sex differences in metabolic brain aging","volume":"116","author":"Goyal","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1073\/pnas.1815917116","article-title":"Persistent metabolic youth in the aging female brain","volume":"116","author":"Goyal","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1001\/jamaneurol.2018.4693","article-title":"Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults","volume":"76","author":"Buckley","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.jalz.2018.04.008","article-title":"Understanding the impact of sex and gender in Alzheimer\u2019s disease: A call to action","volume":"14","author":"Nebel","year":"2018","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.2174\/1567205015666180613111504","article-title":"Sex and Gender Differences in the Brain Cholinergic System and in the Response to Therapy of Alzheimer Disease with Cholinesterase Inhibitors","volume":"15","author":"Giacobini","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1007\/s00018-021-03830-w","article-title":"Alzheimer\u2019s pathogenic mechanisms and underlying sex difference","volume":"78","author":"Zhu","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"eaaz5677","DOI":"10.1126\/scitranslmed.aaz5677","article-title":"A second X chromosome contributes to resilience in a mouse model of Alzheimer\u2019s disease","volume":"12","author":"Davis","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"146305","DOI":"10.1016\/j.brainres.2019.146305","article-title":"Sex difference in CHI3L1 expression levels in human brain aging and in Alzheimer\u2019s disease","volume":"1720","author":"Sanfilippo","year":"2019","journal-title":"Brain Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.biopsych.2021.03.020","article-title":"Sex Differences in the Human Brain Transcriptome of Cases with Schizophrenia","volume":"91","author":"Hoffman","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lee, J., Green, M.F., Nuechterlein, K.H., Swerdlow, N.R., Greenwood, T.A., Hellemann, G.S., Lazzeroni, L.C., Light, G.A., Radant, A.D., and Seidman, L.J. (2020). The effects of age and sex on cognitive impairment in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS) study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232855"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.schres.2017.02.015","article-title":"Sex versus gender differences in schizophrenia: The case for normal personality differences","volume":"189","author":"Lewine","year":"2017","journal-title":"Schizophr. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s10194-018-0849-z","article-title":"Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures","volume":"19","author":"Dai","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s11920-017-0854-y","article-title":"Sex Differences in Trauma-Related Psychopathology: A Critical Review of Neuroimaging Literature (2014\u20132017)","volume":"19","author":"Helpman","year":"2017","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jad.2020.11.087","article-title":"Gender differences of amplitude of low-frequency fluctuations in bipolar disorder: A resting state fMRI study","volume":"280","author":"Jiang","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/ajh\/hpv047","article-title":"State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease","volume":"28","author":"Cohen","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_101","first-page":"166","article-title":"Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: A systematic review and large scale meta-analysis","volume":"15","author":"Vancampfort","year":"2016","journal-title":"World Psychiatry Off. J. World Psychiatr. Assoc."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Kroll, D.S., Feldman, D.E., Biesecker, C.L., McPherson, K.L., Manza, P., Joseph, P.V., Volkow, N.D., and Wang, G.J. (2020). Neuroimaging of Sex\/Gender Differences in Obesity: A Review of Structure, Function, and Neurotransmission. Nutrients, 12.","DOI":"10.3390\/nu12071942"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/obr.12527","article-title":"Sex\/gender differences in neural correlates of food stimuli: A systematic review of functional neuroimaging studies","volume":"18","author":"Chao","year":"2017","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/sj.npp.1300337","article-title":"Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes","volume":"29","author":"Vawter","year":"2004","journal-title":"Neuropsychopharmacology"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Gershoni, M., and Pietrokovski, S. (2017). The landscape of sex-differential transcriptome and its consequent selection in human adults. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0352-z"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.1262110","article-title":"Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans","volume":"348","author":"Consortium","year":"2015","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1126\/science.aaa0355","article-title":"Human genomics. The human transcriptome across tissues and individuals","volume":"348","author":"Ferreira","year":"2015","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"The 1000 Genomes Project Consortium, Abecasis, G.R., Altshuler, D., Auton, A., Brooks, L.D., Durbin, R.M., Gibbs, R.A., Hurles, M.E., and McVean, G.A. (2010). A map of human genome variation from population-scale sequencing. Nature, 467, 1061\u20131073.","DOI":"10.1038\/nature09534"},{"key":"ref_109","first-page":"188","article-title":"Identification and analysis of the human sex-biased genes","volume":"19","author":"Guo","year":"2018","journal-title":"Brief. Bioinform."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1093\/hmg\/ddz090","article-title":"Tissue-specific sex differences in human gene expression","volume":"28","author":"Kassam","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature24265","article-title":"Landscape of X chromosome inactivation across human tissues","volume":"550","author":"Tukiainen","year":"2017","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1038\/ncomms3771","article-title":"Widespread sex differences in gene expression and splicing in the adult human brain","volume":"4","author":"Trabzuni","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/mp.2009.5","article-title":"Transcriptome analysis of male\u2013female differences in prefrontal cortical development","volume":"14","author":"Weickert","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13293-023-00515-w","article-title":"Integrated analysis of robust sex-biased gene signatures in human brain","volume":"14","author":"Wapeesittipan","year":"2023","journal-title":"Biol. Sex Differ."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1080\/00207594.2012.756981","article-title":"A study of the dynamics of sex differences in adulthood","volume":"48","author":"Trofimova","year":"2013","journal-title":"Int. J. Psychol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Hou, H., Uusk\u00fcla-Reimand, L., Makarem, M., Corre, C., Saleh, S., Metcalf, A., Goldenberg, A., Palmert, M.R., and Wilson, M.D. (2017). Gene expression profiling of puberty-associated genes reveals abundant tissue and sex-specific changes across postnatal development. Hum. Mol. Genet.","DOI":"10.1093\/hmg\/ddx246"},{"key":"ref_117","first-page":"3585","article-title":"A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia","volume":"26","author":"Skene","year":"2017","journal-title":"eLife"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature10523","article-title":"Spatio-temporal transcriptome of the human brain","volume":"478","author":"Kang","year":"2011","journal-title":"Nature"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/mp.2009.79","article-title":"Prenatal sex differences in the human brain","volume":"14","author":"Reinius","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"21181","DOI":"10.1038\/srep21181","article-title":"Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages","volume":"6","author":"Shi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Zelco, A., and Joshi, A. (2023). Single-cell analysis of sex and gender differences in the human brain during development and disease. Res. Sq., in submission.","DOI":"10.21203\/rs.3.rs-3023302\/v1"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4049\/jimmunol.2100853","article-title":"Metabolic Sex Dimorphism of the Brain at the Gene, Cell, and Tissue Level","volume":"208","author":"Lee","year":"2022","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3389\/fnins.2019.00392","article-title":"Data-Driven Analysis of Age, Sex, and Tissue Effects on Gene Expression Variability in Alzheimer\u2019s Disease","volume":"13","author":"Brooks","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1038\/s41598-018-20959-0","article-title":"Analysis of microRNA and Gene Expression Profiles in Alzheimer\u2019s Disease: A Meta-Analysis Approach","volume":"8","author":"Moradifard","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.celrep.2017.10.030","article-title":"Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma","volume":"21","author":"Darmanis","year":"2017","journal-title":"Cell Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/B978-0-444-64123-6.00002-3","article-title":"Beyond sex differences and a male-female continuum: Mosaic brains in a multidimensional space","volume":"175","author":"Joel","year":"2020","journal-title":"Handb. Clin. Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1073\/pnas.070039597","article-title":"Navigation-related structural change in the hippocampi of taxi drivers","volume":"97","author":"Maguire","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1373\/clinchem.2018.286781","article-title":"Sex-Specific Versus Overall Clinical Decision Limits for Cardiac Troponin I and T for the Diagnosis of Acute Myocardial Infarction: A Systematic Review","volume":"64","author":"Kimenai","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1081667","DOI":"10.3389\/fendo.2023.1081667","article-title":"Multi-omics and machine learning for the prevention and management of female reproductive health","volume":"14","author":"Kharb","year":"2023","journal-title":"Front. Endocrinol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1676\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:24:24Z","timestamp":1760127864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":129,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["life13081676"],"URL":"https:\/\/doi.org\/10.3390\/life13081676","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}