ArticleJournal of the American Academy of Child and Adolescent Psychiatry2019
Beyond a Binary Classification of Sex: An Examination of Brain Sex Differentiation, Psychopathology, and Genotype.
Article in Journal of the American Academy of Child and Adolescent Psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration.Frontiers in aging neuroscience · 2021Pooled it
- Sex differences in self-reported attention-deficit/hyperactivity disorder symptoms in clinical and population-based cohorts.JCPP advances · 2025Article
- Representative scale-invariant characteristics of male and female brains in magnetic resonance images.Neuroimage. Reports · 2025Article
- Male Sex, Masculinization, Sexual Orientation, and Gynephilia Synergistically Predict Increased Sexual Jealousy.Archives of sexual behavior · 2025Article
- RASGEF1C methylation for the distinguishment and classification of benign and malignant thyroid tumors.Clinical epigenetics · 2025Article
- "Precision Medicine" and the Failed Search for Binary Brain Sex Differences to Address Gender Behavioral Health Disparities.American journal of human biology : the official journal of the Human Biology Council · 2025Review
- Modeling brain sex in the limbic system as phenotype for female-prevalent mental disorders.Biology of sex differences · 2024Article
- A novel framework to predict ADHD symptoms using irritability in adolescents and young adults with and without ADHD.Frontiers in psychiatry · 2024Article
- Insights into Sex and Gender Differences in Brain and Psychopathologies Using Big Data.Life (Basel, Switzerland) · 2023Review
- Sex and gender in neurodevelopmental conditions.Nature reviews. Neurology · 2023Review
- Depressive and Anxiety Symptoms among Children and Adolescents in Rural China: A Large-Scale Epidemiological Study.International journal of environmental research and public health · 2022Article
- Are Sex Differences in Human Brain Structure Associated With Sex Differences in Behavior?Psychological science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
objectiveSex differences in the brain are traditionally treated as binary. We present new evidence that a continuous measure of sex differentiation of the brain can explain sex differences in psychopathology. The degree of sex-differentiated brain features (ie, features that are more common in one sex) may predispose individuals toward sex-biased psychopathology and may also be influenced by the genome. We hypothesized that individuals with a female-biased differentiation score would have greater female-biased psychopathology (internalizing symptoms, such as anxiety and depression), whereas individuals with a male-biased differentiation score would have greater male-biased psychopathology (externalizing symptoms, such as disruptive behaviors).
methodUsing the Philadelphia Neurodevelopmental Cohort database acquired from database of Genotypes and Phenotypes, we calculated the sex differentiation measure, a continuous data-driven calculation of each individual's degree of sex-differentiating features extracted from multimodal brain imaging data (magnetic resonance imaging [MRI] /diffusion MRI) from the imaged participants (n = 866, 407 female and 459 male).
resultsIn male individuals, higher differentiation scores were correlated with higher levels of externalizing symptoms (r = 0.119, p = .016). The differentiation measure reached genome-wide association study significance (p < 5∗10
conclusionThe sex differentiation measure provides an initial topography of quantifying male and female brain features. This demonstration that the sex of the human brain can be conceptualized on a continuum has implications for both the presentation of psychopathology and the relation of the brain with genetic variants that may be associated with brain differentiation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.