About

Gen Shinozaki is an Associate Professor of Psychiatry and Behavioral Sciences at Stanford University, specializing in Medical Psychiatry. He is affiliated with the Center for Artificial Intelligence in Medicine & Imaging (AIMI) at Stanford. His work focuses on integrating artificial intelligence with medical and behavioral sciences to advance healthcare, though specific research areas or contributions are not detailed on the page.

Research topics

• Medicine
• Biology
• Internal medicine
• Computer Science
• Genetics
• Pathology
• Neuroscience
• Ecology
• Immunology
• Psychiatry
• Computational biology
• Bioinformatics

Selected publications

• Impact of cataract surgery on a delirium-related electroencephalography index in older adults

  British Journal of Ophthalmology · 2026-03-23

  article

  The bispectral electroencephalography (BSEEG) method is a simple one-channel quantitative electroencephalography approach that yields a single index, with higher scores previously associated with more severe delirium in older adults. We prospectively measured BSEEG scores in 21 patients over 60 years old before and 1 month after cataract surgery. BSEEG scores significantly decreased after surgery (p=0.001), and this decrease significantly correlated with improvement in best-corrected visual acuity (r=0.52; p=0.02). Improved visual function after cataract surgery was associated with lower BSEEG scores.

  PublisherDOI

• Association of Metformin Use on Postoperative Delirium Risk in Patients with Type 2 Diabetes: A Retrospective Cohort Study

  Delirium · 2026-01-02

  articleOpen access

  Aim Metformin has been reported to improve age-related diseases, including dementia. Prior studies have suggested that metformin use is associated with a decreased risk of delirium. This study aimed to analyze the medical records of surgical patients with comorbid type 2 diabetes to evaluate the relationship between metformin and both postoperative delirium. Method A retrospective cohort study of patients diagnosed with type 2 diabetes who underwent surgery for malignancy in the Departments of Gastrointestinal Surgery and Thoracic Surgery was conducted. A total of 1,159 patients were analyzed to examine metformin use and the incidence of delirium. Results Among the 1,159 patients, 1,026 were classified as the non-metformin-treated diabetes group and 133 as the metformin-treated diabetes group. The incidence of delirium was 17.0% in the non-metformin-treated group and 15.0% in the metformin-treated group. Metformin use was not associated with a reduced risk of delirium after adjustment for confounding factors (Relative risk: 0.94, 95% confidence interval [CI], 0.60~1.45, p = 0.766). The propensity score weighting analyses showed no significant association between metformin use and the incidence of postoperative delirium (Relative risk: 1.51, 95% CI, 0.62~3.69, p = 0.370). Conclusion In this study, metformin use was not significantly associated with postoperative delirium.

  PublisherOA PDFDOI

• Non-linear age-related change in human Interleukin-11 and the receptor subunit alpha DNA methylation

  Biochemistry and Biophysics Reports · 2026-03-19

  articleOpen accessSenior author

  Introduction: and IL-11 receptor subunit alpha (IL-11RA) gene across ages to explore age-related epigenetic patterns that may influence IL-11 production and pathway sensitivity. Methods: 1RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations. Results: 1RA CpG sites in the TSS1500 and 3'UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age. Conclusion: 1RA suggest non-linear age-related regulation that may influence IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.

  PublisherDOI

• Point-of-Care Bispectral Electroencephalogram (BSEEG) As a New Tool in Detecting Immune Effector Cell Associated Neurotoxicity (ICANS) in Patients Treated with Chimeric Antigen Receptor T-Cell (CAR-T)

  Transplantation and Cellular Therapy · 2025-02-01

  articleSenior author
  PublisherDOI

• Epigenetic markers of middle-age: non-linear DNA methylation changes with aging in humans

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-16

  preprintOpen accessSenior authorCorresponding

  Abstract Background Human DNA is known to exhibit an overall tendency toward demethylation with aging. However, assuming a simple linear relationship between DNA methylation and age does not align with the phenotype of human development and the aging process. This study aimed to investigate the existence of DNA methylation patterns with peaks or troughs at specific ages in addition to simple linear changes. Methods A large-scale dataset of genome-wide DNA methylation data from 10,420 individuals was analyzed. Hierarchical multiple regression models were applied to detect patterns of the association between age and DNA methylation: linear increase, linear decrease, U-shaped curve, and inverse U-shaped curve. Results Among the 864,627 CpG sites analyzed, 8.4% exhibited an increase in DNA methylation with age, 23.9% showed a decrease, and 5.5% were better explained by a quadratic model (P < 5.7815×10 ). Within the non-linear subset, inverse U-shaped CpG sites peaking in methylation during middle age were predominant. Genes exhibiting quadratic association patterns between DNA methylation and age, and those linked to diseases with common onset during middle age, were also detected. Conclusions Non-linear age-related DNA methylation patterns, with peaks or troughs occurring at specific ages, were detected. This suggests that humans do not simply age linearly, but that programmed mechanisms or cascade-like processes may exist to promote or suppress the expression of specific genes at certain ages, contributing onset of certain diseases at specific timings.

  PublisherOA PDFDOI

• Genome-Wide DNA Methylation Profiles of Long-Term Cognitive Decline after Delirium in Intensive Care Unit Patients

  Anesthesia & Analgesia · 2025-09-16

  articleSenior author

  BACKGROUND: To date, no studies have reported on the differences in genome-wide DNA methylation (DNAm) profiles between delirium patients with and without long-term cognitive decline (LTCD). This study aimed to identify epigenetic markers associated with LTCD after delirium using blood samples from intensive care unit (ICU) patients. METHODS: Blood DNA samples from 104 patients (86 delirium patients and 18 nondelirium patients) were analyzed using the Illumina EPIC array genome-wide platform. We investigated the differences in DNAm related to the presence or absence of LTCD among delirium patients, nondelirium patients, and the entire cohort. Enrichment analyses were conducted using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome terminology (KEGG). RESULTS: Among the 20 top hits of differentially methylated cytosine-phosphate-guanine (CpG) sites associated with LTCD in patients with delirium, CpG located within the major histocompatibility complex (MHC) region on chromosome 6 (cg11103845) was significantly associated after false discovery rate (FDR) correction (FDR-adjusted P = .034). Enrichment analysis revealed immune-related pathways associated with LTCD. Although not statistically significant, MHC class II-related pathways, such as "MHC class II receptor activity" and "MHC class II protein complex assembly," were also ranked among the top hits. CONCLUSIONS: This genome-wide DNAm analysis focused on LTCD after delirium highlights differentiating epigenetic signals related to MHC class II and immune processes. These findings provide initial evidence that epigenetic processes may play a crucial role in the pathophysiological mechanisms underlying LTCD after delirium.

  PublisherDOI

• Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-14 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances in consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address the knowledge gap, we investigated DNA methylation profiles and gene expression changes in brain cells from POD and non-POD patients who underwent brain resection surgery for medication refractory epilepsy. DNA methylation analysis revealed alteration in epigenetic status of immune and inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly in microglia, where neuroinflammation was strongly enhanced, consistent with epigenetic findings. Astrocytes exhibited changes in synapse-related functions and migration. Furthermore, downstream analysis indicated similarities between POD-associated glial cell states and pathologies such as encephalitis and dementia. Overall, this study-the first multi-omics analysis of brain tissue from POD patients-provides direct evidence of glial cell contributions to POD pathogenesis, and highlights potential therapeutic targets.

  PublisherOA PDFDOI

• Non-linear Age-related Change in Human Interleukin-11 and the receptor subunit alpha DNA Methylation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-08

  preprintOpen accessSenior authorCorresponding

  Abstract Introduction Interleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking down IL11 in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in the IL11 and IL-11 receptor subunit alpha (IL-11RA) gene across ages to reveal how aging might influence IL-11 production and sensitivity. Methods A genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within the IL11 and IL11RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations. Results The database comprised 10,297 samples (5,156 males and 5,141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority of IL11 and IL11RA CpG sites in the TSS1500 and 3’UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age. Conclusion The observed inverse U-shaped DNAm patterns in the IL11 and IL11RA suggest n non-linear, age-related regulation of IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.

  PublisherOA PDFDOI

• Bedside EEG for rapid diagnosis of delirium

  Neurotherapeutics · 2025-10-22 · 1 citations

  reviewOpen accessSenior author

  Delirium is a frequent complication among older adults and is linked to higher mortality, longer hospital stays, and greater healthcare expenditure. Although its clinical relevance is well recognized, routine diagnosis remains challenging because existing tools rely largely on the observation of fluctuating symptoms, which can easily be overlooked in daily practice. Electroencephalography (EEG) provides an objective measure of brain activity, and characteristic changes such as generalized slowing have been consistently described in patients with delirium. Despite these established findings, the conventional EEG setup is technically demanding and not well suited for repeated use in general hospital wards. In recent years, portable point-of-care (POC) EEG systems have been developed, allowing recordings with a limited number of electrodes at the bedside. Several clinical studies have reported that these devices are able to detect delirium with acceptable accuracy, while also offering practical advantages such as rapid deployment and use by non-specialist staff. Among the approaches investigated, the bispectral EEG (BSEEG) method has attracted particular attention. A higher BSEEG score has been shown to correlate with delirium severity and to predict adverse outcomes, including reduced survival, even in patients who did not present with overt clinical symptoms. Beyond the clinical setting, experimental work has applied EEG and BSEEG to rodent models of delirium induced by inflammation or surgery. These studies have highlighted associations between EEG slowing, microglial activation, and behavioral disturbances, suggesting that electrophysiological changes may provide a translational link between basic mechanisms and clinical phenomena. Preclinical data also indicate that BSEEG could serve as a quantitative tool for assessing treatment response in experimental models. Taken together, these findings support the potential of simplified EEG platforms to complement current diagnostic strategies. If further validated in larger, real-world cohorts, bedside EEG may become a practical adjunct for the early recognition of delirium and the monitoring of disease progression, with implications for both patient outcomes and mechanistic research.

  PublisherOA PDFDOI

• Delirium Detection Using Point-of-Care Single-Channel EEG: A Pilot Study

  Innovation in Aging · 2025-12-01

  articleOpen access

  Abstract Delirium is a common yet underdiagnosed medical emergency involving acute deficits in cognition and attention. It affects over 20% of hospitalized patients and up to 80% of ICU patients, with increased prevalence in older adults. Delirium is associated with increased mortality, prolonged hospitalization, long-term cognitive decline, and substantial healthcare costs. However, current screening tools are subjective and difficult to implement consistently. Traditional EEGs show diagnostic utility; however, they are costly and require specialized interpretation. We conducted a prospective pilot study evaluating a point-of-care, single-channel EEG device for delirium detection in hospitalized older adults. EEG spectra were utilized to calculate a ‘bispectral EEG’ (BSEEG) score reflecting the ratio of slow to fast brain waves. Twenty-two postoperative patients (mean age 75; 59.09% female) were assessed daily for up to seven days using both the BSEEG and the gold standard 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). ROC analysis was utilized to determine an optimal threshold BSEEG score to indicate delirium positivity. BSEEG scores were significantly higher in the 3D-CAM-positive group than in the 3D-CAM-negative group (1.60 and 1.45, respectively; p < 0.05). A BSEEG threshold of 1.5 demonstrated 77.78% sensitivity and 56.10% specificity for delirium. In contrast, route clinical screenings (Delirium Triage Screen and Brief CAM) showed 0.00% sensitivity and 96.30% specificity, and failed to detect all true delirium cases. Although further validation in larger cohorts is needed, these findings suggest that the point-of-care single-channel EEG is a promising, non-invasive screening tool for delirium screening, particularly in fast-paced clinical settings.

  PublisherOA PDFDOI

Recent grants

• Epigenetics Biomarker of Post Operative Delirium and Long Term Cognitive Decline among Elderly Dementia Patients

  NIH · $3.4M · 2024–2029

• Identification of Epigenetics Correlates between Brain and Peripheral Tissues

  NIH · $3.0M · 2021–2025

• Epigenetic Investigation of Trauma in PTSD and Depression

  NIH · $718k · 2015–2019

• I-Corps: Delirium Prediction and Screening by Non-Invasive Point-of-Care

  NSF · $50k · 2016–2018

Frequent coauthors

• Takehiko Yamanashi

  Stanford University

  96 shared

• Kaitlyn J. Crutchley

  University of Nebraska Medical Center

  50 shared

• Pedro S. Marra

  University of Iowa

  46 shared

• Elizabeth A. Regan

  42 shared

• Nadia E. Wahba

  Oregon Health & Science University

  35 shared

• Barry J. Make

  National Jewish Health

  34 shared

• Masaaki Iwata

  Tottori University

  33 shared

• Tsuyoshi Nishiguchi

  Tottori University

  32 shared