Gene-environment interactions explain a substantial portion of variability of common neuropsychiatric disorders

Zhang, Hanxin; Khan, Atif Ali; Rzhetsky, Andrey

doi:10.1016/j.xcrm.2022.100736

Cited by 4 publications

(1 citation statement)

References 39 publications

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“…16 Such studies can result in causal associations between environmental factors and diseases, on population-wide scales. 17 A recent study of administrative medical health records of 150 million patients from the US and Denmark could infer trajectories for different combinations of diseases, starting in early life. 18 Characterization of such trajectories, and their environmental/molecular associations could be starting points for construction of dynamic DTs.…”

Section: Construction Of Digital Twins For Predictive Preventive and ...mentioning

confidence: 99%

Digital Twins for Predictive, Preventive Personalized, and Participatory Treatment of Immune-Mediated Diseases

Benson

2023

ATVB

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Digital twins are computational models of complex systems, which aim to understand and optimize those systems more effectively than would be possible in real life. Ideally, digital twins can be translated to individual patients, to characterize and computationally treat their diseases with thousands of drugs, to select the drug or drugs that cure the patients. The background problem is that many patients do not respond adequately to drug treatment. This problem reflects a wide gap between the complexity of diseases and clinical practice. Each disease may involve altered interactions between thousands of genes that vary between different cell types in different organs. To our knowledge, these altered interactions have not been characterized on a genome-, cellulome-, and organ-wide scale in any disease. Thus, clinical translation of the digital twin ideal for predictive, preventive, personalized and participatory treatment involves formidable challenges, which are close to the limits of, or beyond today’s technologies. Here, I discuss recent developments and challenges in relation to that ideal focusing on immune-mediated inflammatory diseases, as well as examples from other diseases.

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Section: Construction Of Digital Twins For Predictive Preventive and ...mentioning

confidence: 99%

Digital Twins for Predictive, Preventive Personalized, and Participatory Treatment of Immune-Mediated Diseases

Benson

2023

ATVB

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Shifting the trajectory of therapeutic development for neurological and psychiatric disorders

Krainc,

Martin,

Casey

et al. 2023

Sci. Transl. Med.

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Clinical trials for central nervous system disorders often enroll patients with unrecognized heterogeneous diseases, leading to costly trials that have high failure rates. Here, we discuss the potential of emerging technologies and datasets to elucidate disease mechanisms and identify biomarkers to improve patient stratification and monitoring of disease progression in clinical trials for neuropsychiatric disorders. Greater efforts must be centered on rigorously standardizing data collection and sharing of methods, datasets, and analytical tools across sectors. To address health care disparities in clinical trials, diversity of genetic ancestries and environmental exposures of research participants and associated biological samples must be prioritized.

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Does Morphine Exposure Before Gestation Change Anxiety-Like Behavior During Morphine Dependence in Male Wistar Rats?

Sabzevari,

Rohbani,

Sadeghi-Adl

et al. 2023

Addict Health

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Background: Anxiety is one of the comorbid disorders of opioid addiction, which leads to opioid abuse or persuades people to engage in opioid abuse. Evidence revealed that morphine exposure before conception changes the offspring’s phenotype. The current study aimed to investigate the influence of morphine dependence and abstinence on anxiety-like behavior in morphine-exposed and drug-naïve offspring. Methods: Adult male and female rats were treated with morphine or vehicle for 21 days. Then, all rats were left without drug treatment for 10 days. A morphine-exposed female rat was mated with either a vehicle-exposed or morphine-abstinent male. According to parental morphine exposure, the offspring were categorized into four distinct groups: (1) control (both drug-naïve parents), (2) paternal morphine-exposed, (3) maternal morphine-exposed, and (4) biparental morphine-exposed. The anxiety-like behavior was measured in adult male offspring using open field and elevated plus-maze tests before morphine exposure (naïve), 21 days after morphine exposure (dependence), and ten days after the last morphine exposure (abstinence). Findings: The results indicated that anxiety-like behavior increased before morphine exposure in maternal and biparental morphine-exposed offspring (P<0.05). However, after morphine exposure, the anxiety level did not change among the groups. Ten days after the last morphine exposure, anxiety-like behavior increased only in biparental morphine-exposed offspring (P<0.05). Conclusion: The offspring of morphine-abstinent parents exhibited an anxious phenotype. Disruption of the HPA axis was seen in the progeny of maternal and biparental morphine-exposed rats. Indeed, morphine exposure for 21 days did not change anxiety-like behavior in these offspring which might be correlated to disruption of HPA axis in them.

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Gene-environment interactions explain a substantial portion of variability of common neuropsychiatric disorders

Cited by 4 publications

References 39 publications

Digital Twins for Predictive, Preventive Personalized, and Participatory Treatment of Immune-Mediated Diseases

Digital Twins for Predictive, Preventive Personalized, and Participatory Treatment of Immune-Mediated Diseases

Shifting the trajectory of therapeutic development for neurological and psychiatric disorders

Does Morphine Exposure Before Gestation Change Anxiety-Like Behavior During Morphine Dependence in Male Wistar Rats?

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