Causal effects of serum testosterone levels on brain volume: a sex-stratified Mendelian randomization study

Niu, Peng-Peng; Wang, X; Xu, Y-M

doi:10.1007/s40618-023-02028-0

Cited by 4 publications

(2 citation statements)

References 59 publications

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“…When evaluating the causal relationships between eight iron-sensitive imaging features, nine DTI features and RLS, the maximum sample overlap rates were 6.25% (30,056 / 480,982) and 7.61% (36,642 / 480,982), respectively, due to probable common participants from the UK Biobank. Since these overlaps were relatively small, the resulting bias was deemed negligible [61][62][63] . However, when exploring the relationship between ADHD and the age of first birth, the maximum sample overlap rate was 25.42% (137,993 / 542,901) due to participants from the deCODE cohort.…”

Section: Evaluation and Correction For The Bias From Sample Overlapmentioning

confidence: 99%

Shared genetic architecture and causal pathways between attention deficit hyperactivity disorder and restless legs syndrome

Li,

Zhang

et al. 2024

Preprint

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Previous studies have revealed a significant overlap between ADHD and RLS populations, with shared pathological mechanisms such as dopaminergic function and iron metabolism deficits. However, the genetic mechanisms underlying these connections remain unclear. In our study, we conducted a genome-wide genetic correlation analysis to confirm a shared genetic structure between ADHD and RLS. We identified five pleiotropic loci through PLACO analysis, with colocalization analysis revealing a shared causal genetic variant, rs12336113, located in an intron of the PTPRD gene within one of these loci. Additionally, we identified 14 potential shared genes and biological pathways between these diseases. Protein-protein interaction analysis demonstrated close interactions among six genes: PTPRD, MEIS1, MAP2K5, SKOR1, BTBD9, and TOX3. We further investigated gene-driven causal pathways using univariable Mendelian randomization (MR), multivariable MR, and Network MR analyses. Our findings indicate that ADHD may indirectly promote the onset of RLS by advancing the age of first birth, while RLS could indirectly contribute to ADHD by reducing fractional anisotropy in body of corpus callosum. Notably, an increase in radial diffusivity, rather than a decrease in axial diffusivity, played a crucial role in this process. In conclusion, our research supports a close genetic link between ADHD and RLS, identifying PTPRD as the most likely pleiotropic gene between these conditions. Moreover, ADHD may indirectly promote RLS onset by advancing the age of first birth, while RLS may indirectly promote ADHD onset by causing demyelination in body of corpus callosum.

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Section: Evaluation and Correction For The Bias From Sample Overlapmentioning

confidence: 99%

Shared genetic architecture and causal pathways between attention deficit hyperactivity disorder and restless legs syndrome

Li,

Zhang

et al. 2024

Preprint

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“…Testosterone has neuroprotective effects on the brain, and studies have shown the impact of testosterone on cognition [71]. Hypogonadal men demonstrate an impairment in spatial abilities, memory, and attention, and the administration of testosterone and DHT gel improved cognition [72,73].…”

Section: Testosterone Impact On Cognition Mood and Energymentioning

confidence: 99%

Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood

Reiss,

Gulkarov,

Pinkhasov

et al. 2023

Medicina

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Prostate cancer is the second leading cause of cancer death in men in the United States. Androgen deprivation therapy (ADT) is currently the primary treatment for metastatic prostate cancer, and some studies have shown that the use of anti-androgen drugs is related to a reduction in cognitive function, mood changes, diminished quality of life, dementia, and possibly Alzheimer’s disease. ADT has potential physiological effects such as a reduction in white matter integrity and a negative impact on hypothalamic functions due to the lowering of testosterone levels or the blockade of downstream androgen receptor signaling by first- and second-generation anti-androgen drugs. A comparative analysis of prostate cancer patients undergoing ADT and Alzheimer patients identified over 30 shared genes, illustrating common ground for the mechanistic underpinning of the symptomatology. The purpose of this review was to investigate the effects of ADT on cognitive function, mood, and quality of life, as well as to analyze the relationship between ADT and Alzheimer’s disease. The evaluation of prostate cancer patient cognitive ability via neurocognitive testing is described. Future studies should further explore the connection among cognitive deficits, mood disturbances, and the physiological changes that occur when hormonal balance is altered.

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Causal influences of testosterone on brain structure change rate: A sex-stratified Mendelian randomization study

Lian,

Bai,

et al. 2025

The Journal of Steroid Biochemistry and Molecular Biology

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Causal effects of serum testosterone levels on brain volume: a sex-stratified Mendelian randomization study

Cited by 4 publications

References 59 publications

Shared genetic architecture and causal pathways between attention deficit hyperactivity disorder and restless legs syndrome

Shared genetic architecture and causal pathways between attention deficit hyperactivity disorder and restless legs syndrome

Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood

Causal influences of testosterone on brain structure change rate: A sex-stratified Mendelian randomization study

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