Plasma homocysteine in first-episode schizophrenia

Taweel, Mohamed El Sayed El; Elshafie, Taghreed; Heba, K.

doi:10.1097/01.xme.0000526695.73173

Middle East Current Psychiatry

2018

DOI: 10.1097/01.xme.0000526695.73173

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Plasma homocysteine in first-episode schizophrenia

Mohamed El Sayed El Taweel¹,

Taghreed Elshafie²,

K. Heba³

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2021

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“…Decreasing homocysteic acid, a homocysteine metabolite, has been shown to decrease serum Creactive protein in Kawasaki Disease—a disease similar to Multisystem Inflammatory Syndrome in Children (MIS-C) [6] . High Hcy has also been found in first-episode schizophrenia [7] ; the MTHFR C677T polymorphism that contributes to Hcyimbalances has also been associated with schizophrenia [8] ; and schizophrenia was recently linked to an increased risk of death in COVID-19 [9] . Given these numerous correlates, it is relevant to explore how Hcy may be impacting COVID-19 severity.…”

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confidence: 99%

Further comment on articles pertaining to: “Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19”

Berbert¹

2021

Medical Hypotheses

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Recent studies have found a correlate between higher homocysteine (Hcy) levels and higher COVID-19 mortality rates. In October 2020, researchers in Italy noted vasculitic damage in seriously ill patients and suspected Hcy played a contributing role. After initially observing a small cohort of only 40 patients, they conducted a study of Hcy levels in 313 patients and definitively identified Hcy as a predictive marker for COVID-19 mortality risk [1] , [2] . In addition, Hcy is associated with many conditions that share comorbidity with SARS-CoV-2, including cardiovascular disease, diabetes, and stroke [3] , [4] . Hcy is found in higher quantities in men, Hcy levels increase with age, and high Hcy is also associated with poor nutrition/low folate which may correlate to socioeconomic disparities for COVID-19 fatalities within the United States [5] . Decreasing homocysteic acid, a homocysteine metabolite, has been shown to decrease serum Creactive protein in Kawasaki Disease—a disease similar to Multisystem Inflammatory Syndrome in Children (MIS-C) [6] . High Hcy has also been found in first-episode schizophrenia [7] ; the MTHFR C677T polymorphism that contributes to Hcyimbalances has also been associated with schizophrenia [8] ; and schizophrenia was recently linked to an increased risk of death in COVID-19 [9] . Given these numerous correlates, it is relevant to explore how Hcy may be impacting COVID-19 severity. Three Hcy-related GPCRs have repeatedly surfaced in studies on SARS-CoV-2; namely, AT1R, B2 , and CXCR6. I hypothesize that Hcy interference with these GPCRs may be contributing to COVID-19 severity in two primary ways. Firstly, Hcy can act as an alternate agonist to AT1R at c289s [10] , which could exacerbate the reninangiotensin system (RAS) imbalances induced by SARS-CoV-2 interactions with angiotensin-converting enzyme 2 (ACE2). A recent paper also hypothesized that SARS-CoV-2 may be disrupting GPCR signaling and dysregulating adenylyl cyclase [11] . Because AT1 -B2 receptor heterodimer activity is known to enhance Gi/o and Gq/11 activation, SARS-CoV-2 GPCR signaling disruption may be attributed to potential heterodimeric overexpression in severe COVID-19 as well as to potential heterodimeric hypersensitivity to c289s Hcy agonism. Secondly, Hcy upregulation of CXCL16 [12] in conjunction with SARS-CoV-2 possible binding to CXCL16 and chemotactic disabling [13] could be problematic in those with a chromosome 3 locus that exhibits lower CXCR6 expression [14] .

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confidence: 99%

Further comment on articles pertaining to: “Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19”

Berbert¹

2021

Medical Hypotheses

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Plasma homocysteine in first-episode schizophrenia

Cited by 1 publication

References 36 publications

Further comment on articles pertaining to: “Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19”

Further comment on articles pertaining to: “Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19”

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