The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure

Tan, Geoffrey; Chu, Carlton; Lee, Yu Teng; Tan, Clarence Chih King; Ashburner, John; Wood, Nicholas W.; Frackowiak, R. S. J.

doi:10.1016/j.neuroimage.2020.117087

Cited by 12 publications

(20 citation statements)

References 106 publications

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“…Notably, evidence suggests that sex steroids influence brain structure in regions that often overlapped with those showing sex-by-diagnosis differences in this review ( Tan et al, 2020 ). Specifically, a recent study in NT adults found that sex-steroid receptor allele efficiency influenced regional GM and WM volumes, predominantly within regions of the limbic, ventral attention, and default mode networks as well as across several projection and association WM tracts ( Tan et al, 2020 ). The overlap between regions showing NT sex differences and regions expressing sex-by-diagnosis effects in this review may suggest an interaction between sex steroids and ASD-related genetics in brain development.…”

Section: Discussionmentioning

confidence: 79%

“…Among the whole-brain approaches investigating sex-by-diagnosis differences, most effects fell within structures that also show NT sex differences, including limbic, default mode, ventral attention, cerebellar, and visual regions ( Bakker, 2018 , Rehbein et al, 2020 , Tan et al, 2020 , Vijayakumar et al, 2018 ). For example, sex-by-diagnosis effects in morphometry studies generally fell within regions associated with the limbic, default mode, visual, as well as somatomotor (especially auditory/language regions) networks (see table 1 for a summary of sMRI study results; Cauvet, 2019 , Ecker et al, 2017 , Irimia et al, 2017 , Postema et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, interpreting brain-based sex differences in ASD from an endocrine and genetic sex perspective may reveal new targets for future basic science and biomarker research. To date, most human research on the effects of sex steroids on the brain comes from sMRI studies ( Bakker, 2018 , Rehbein et al, 2020 , Tan et al, 2020 ). Notably, evidence suggests that sex steroids influence brain structure in regions that often overlapped with those showing sex-by-diagnosis differences in this review ( Tan et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…To date, most human research on the effects of sex steroids on the brain comes from sMRI studies ( Bakker, 2018 , Rehbein et al, 2020 , Tan et al, 2020 ). Notably, evidence suggests that sex steroids influence brain structure in regions that often overlapped with those showing sex-by-diagnosis differences in this review ( Tan et al, 2020 ). Specifically, a recent study in NT adults found that sex-steroid receptor allele efficiency influenced regional GM and WM volumes, predominantly within regions of the limbic, ventral attention, and default mode networks as well as across several projection and association WM tracts ( Tan et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence to suggest that regional brain volumes in ASD might be disproportionally affected by androgen exposure, in particular during early development. For example, it has been found that ventromedial prefrontal and dorsal anterior cingulate volumes are modulated by androgen receptor (AR) allele efficiency ( Tan et al, 2020 ). In this review, females with ASD showed an association between higher ASD symptom severity and thicker ventromedial prefrontal and dorsal anterior cingulate cortices ( Bedford et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings

Walsh

Wallace

Gallegos

et al. 2021

NeuroImage: Clinical

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Highlights Evidence suggests neuroimaging-based sex differences in ASD are age-dependent. Most studies collapse across age, possibly masking sex-by-diagnosis effects. Sex-by-diagnosis effects overlap with regions showing typical sexual dimorphism. Findings discussed in the context of genetic and endocrine sex effects on the brain. Future research would benefit from a lifespan approach in large-sample studies.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings

Walsh

Wallace

Gallegos

et al. 2021

NeuroImage: Clinical

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Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Chen,

Yang,

et al. 2024

Human Brain Mapping

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Although Postpartum depression (PPD) and PPD with anxiety (PPD‐A) have been well characterized as functional disruptions within or between multiple brain systems, however, how to quantitatively delineate brain functional system irregularity and the molecular basis of functional abnormalities in PPD and PPD‐A remains unclear. Here, brain sample entropy (SampEn), resting‐state functional connectivity (RSFC), transcriptomic and neurotransmitter density data were used to investigate brain functional system irregularity, functional connectivity abnormalities and associated molecular basis for PPD and PPD‐A. PPD‐A exhibited higher SampEn in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) than healthy postnatal women (HPW) and PPD while PPD showed lower SampEn in PPC compared to HPW and PPD‐A. The functional connectivity analysis with MPFC and PPC as seed areas revealed decreased functional couplings between PCC and paracentral lobule and between MPFC and angular gyrus in PPD compared to both PPD‐A and HPW. Moreover, abnormal SampEn and functional connectivity were associated with estrogenic level and clinical symptoms load. Importantly, spatial association analyses between functional changes and transcriptome and neurotransmitter density maps revealed that these functional changes were primarily associated with synaptic signaling, neuron projection, neurotransmitter level regulation, amino acid metabolism, cyclic adenosine monophosphate (cAMP) signaling pathways, and neurotransmitters of 5‐hydroxytryptamine (5‐HT), norepinephrine, glutamate, dopamine and so on. These results reveal abnormal brain entropy and functional connectivities primarily in default mode network (DMN) and link these changes to transcriptome and neurotransmitters to establish the molecular basis for PPD and PPD‐A for the first time. Our findings highlight the important role of DMN in neuropathology of PPD and PPD‐A.

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Deep Learning Classification Based on Raw MRI Images

Moguilner,

Ibañez

2024

Neuromethods

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In this chapter, we describe a step-by-step implementation of an automated anatomical MRI feature extractor based on artificial intelligence machine learning for classification. We applied the DenseNet—a state-of-the-art convolutional neural network producing more robust results than previous deep learning network architectures—to data from male (n = 400) and female (n = 400), age-, and education- matched healthy adult subjects. Moreover, we illustrate how an occlusion sensitivity analysis provides meaningful insights about the relevant information that the neural network used to make accurate classifications. This addresses the “black-box” limitations inherent in many deep learning implementations. The use of this approach with a specific dataset demonstrates how future implementations can use raw MRI scans to study a range of outcome measures, including neurological and psychiatric disorders.

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The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure

Cited by 12 publications

References 106 publications

Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings

Brain-based sex differences in autism spectrum disorder across the lifespan: A systematic review of structural MRI, fMRI, and DTI findings

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Deep Learning Classification Based on Raw MRI Images

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