Sex differences in the developing brain: insights from multimodal neuroimaging
Open accessAbstract
Youth (including both childhood and adolescence) is a period when the brain undergoes dramatic remodeling and is also a time when neuropsychiatric conditions often emerge. Many of these illnesses have substantial sex differences in prevalence, suggesting that sex differences in brain development may underlie differential risk for psychiatric symptoms between males and females. Substantial evidence documents sex differences in brain structure and function in adults, and accumulating data suggests that these sex differences may be present or emerge during development. Here we review the evidence for sex differences in brain structure, white matter organization, and perfusion during development. We then use these normative differences as a framework to understand sex differences in brain development associated with psychopathology. In particular, we focus on sex differences in the brain as they relate to anxiety, depression, psychosis, and attention-deficit/hyperactivity symptoms. Finally, we highlight existing limitations, gaps in knowledge, and fertile avenues for future research.
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Other studies have shown contradictory results regarding the influence of brain structures on sex differences in anxiety.
“However, other studies, as exposed in Kaczkurkin et al., 68 have shown contradictory results regarding the influence of brain structures on sex differences in anxiety.”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [68]
The Relevance for Psychopathology section reports mixed findings on brain structure and anxiety, including increased and decreased regional volumes across studies. It does not say those contradictory structural findings concern sex differences in anxiety; its discussion of sex differences instead focuses on brain perfusion. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSex differences in anxiety disorders may be due to differences in brain structures involved in emotional regulation, which explain the difference in processing negative information.
“other studies show that differences in anxiety disorders between sexes may be due to (a) differences in the brain structures involved in emotional regulation, which explain the difference in the processing of negative information,32,39,68”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [68]
The “Relevance for Psychopathology” section links sex differences in anxiety-related symptoms to blood flow in affective brain regions, including the amygdala. It also says evidence for structural differences in anxiety is mixed. It does not establish that differences in brain structure explain sex differences in processing negative information; no page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOf the 44 documents, 31 were empirical/quantitative studies and 13 were reviews.
“Of the 44 documents, 31 were empirical/quantitative studies30–60 and 13 were reviews.61–73”
From Factors associated with gender and sex differences in anxiety prevalence and comorbidity: A systematic review (2022) · cites this paper as [68]
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Farhane-Medina, N. Z., Luque, B., Tabernero, C., & Castillo-Mayén, R. (2022) · Science Progress · doi:10.1177/00368504221135469 · Cited by 409 · see citing works
“Kaczkurkin et al.68 USA Biological factors To review sex differences in the development of brain structures, Related to anxiety, there are sex differences in cerebral blood flow (Continued) anxiety had more adaptive psychosocial functioning than boys with anxiety.”
BackgroundInfluentialNeuroscience and Sex/Gender: Looking Back and Forward
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Evidence for dissociable linkage of dimensions of psychopathology to brain structure in youths
Kaczkurkin, A. N., Park, S. S., Sotiras, A., Moore, T. M., Calkins, M. E., Cieslak, M., Rosen, A. F. G., Ciric, R., Xia, C. H., Cui, Z., et al. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.18070835 · Cited by 110 · see citing works
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Homework, sleep insufficiency and adolescent neurobehavioral problems: Shanghai Adolescent Cohort
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Liu, H., Tang, J., Zhao, Z., Zhou, Y., Ding, H., Liu, N., Ji, Y., Wang, P., Wu, X., Liu, F., et al. (2026) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2026.101820
- Authors
- Kaczkurkin, A. N., Raznahan, A., & Satterthwaite, T. D.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Corresponding author
- Satterthwaite, Theodore D.
- Venue
- Neuropsychopharmacology
- Published
- 2018-06-06
- Volume
- 44
- Issue
- 1
- Pages
- 71-85
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6235840
- OpenAlex
- W2806051693
- Cited by
- 403
- References
- 206
- Citations by year
- 2026: 37 · 2025: 62 · 2024: 63 · 2023: 84 · 2022: 48 · 2021: 54 · 2020: 38 · 2019: 15 · 2018: 2
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Children's Hospital of Philadelphia
- University of Pennsylvania (K12 HD085848)
- National Alliance for Research on Schizophrenia and Depression
- University of Pennsylvania Health System
- National Institutes of Health (NCT00001246, 89-M-0006)
- National Institute of Mental Health (NCT00001246, 89-M-0006, R01MH107703, ZIAMH002794, R01MH113550)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD085848)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- sex differences, brain development, youth, white matter organization, cerebral perfusion, brain structure, neuropsychiatric disorders, anxiety, depression, psychosis, attention deficit hyperactivity disorder, adolescence
- MeSH terms
- Adolescent, Mental Disorders, Brain, Child, Female, Humans, Male, Sex Characteristics, Neuroimaging, Multimodal Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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