The role of COMT gene Val108/158Met polymorphism in suicidal behavior: systematic review and updated meta-analysis

Thelma Beatriz González-Castro,1 Yazmín Hernández-Díaz,1 Isela Esther Juárez-Rojop,2 María Lilia López-Narváez,3 Carlos Alfonso Tovilla-Zárate,4 Julian Ramírez-Bello,5 Nonanzit Pérez-Hernández,6 Alma Delia Genis-Mendoza,7 Ana Fresan,8 Crystell Guadalupe Guzmán-Priego2 1Multidisciplinary Academic Division of Jalpa de Méndez, Juarez Autonomous University of Tabasco, Jalpa de Méndez, Tabasco, Mexico; 2Multidisciplinary Academic Division of Health Sciences, Juarez Autonomous University of Tabasco, Villahermosa, Tabasco, Mexico; 3General Hospital of Yajalon, Ministry of Health, Yajalon, Chiapas, Mexico; 4Multidisciplinary Academic Division of Comalcalco, Juarez Autonomous University of Tabasco, Comalcalco, Tabasco, Mexico; 5Research Unit, Juárez Hospital of Mexico, Ministry of Health, Mexico City, Mexico; 6Department of Molecular Biology, National Institute of Cardiology, Mexico City, Mexico; 7Psychiatric Care Services, National Institute of Genomic Medicine (INMEGEN), Health Secretary, Ministry of Health, Mexico City, Mexico; 8Sub-direction of Clinical Research, Children’s Psychiatric Hospital “Dr. Juan N. Navarro”, Mexico City, Mexico Background: It is accepted that there is a genetic factor that influences the risk of suicidal behavior. The catechol-O-methyltransferase (COMT) gene, especially the Val108/158Met polymorphism, has been associated with suicide; however, no conclusive outcome has been attained. Therefore, the aim of the present study was to assess the role of COMT Val108/158Met in suicidal behavior throughout an updated meta-analysis. Methods: We performed an online search using PubMed and Web of Science (up to March 2017). Our systematic review included case-control studies of individuals who attempted suicide and completed suicide. We tested allelic, homozygous, heterozygous, dominant, and recessive inheritance models. The meta-analysis was performed in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results: The meta-analysis comprised 17 studies, which included 3,282 cases and 3,774 controls, and showed that when evaluating the overall population, the Val108/158Met polymorphism of COMT was not associated with suicidal behavior in any of the inheritance models; however, the subanalyses showed that this polymorphism exhibits a risk factor in males and a protective effect in females. Additionally, it conveyed a risk factor in Asian populations when using the allelic (OR 1.25; CI: 1.04–1.51) and recessive models (OR 1.32; CI: 1.03–1.68). Conclusion: Our updated meta-analysis suggests a possible association between COMT Val108/158Met and suicidal behavior in Asian populations. However, in view of the small number of studies, these results should be considered exploratory. We recommend that more studies be performed with larger samples. Keywords: suicide, epidemiology, mental health, risk factor

Aftereffects in Epigenetic Age Related to Cognitive Decline and Inflammatory Markers in Healthcare Personnel with Post-COVID-19: A Cross-Sectional Study

Germán Alberto Nolasco-Rosales,1,&ast; Cecilia Yazmin Alonso-García,1,&ast; David Gustavo Hernández-Martínez,1 Mario Villar-Soto,2 José J Martínez-Magaña,3 Alma Delia Genis-Mendoza,4 Thelma Beatriz González-Castro,5 Carlos Alfonso Tovilla-Zarate,6 Crystell Guadalupe Guzmán-Priego,1 Mirian Carolina Martínez-López,1 Humberto Nicolini,7 Isela Esther Juárez-Rojop1 1División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco, Villahermosa, Tabasco, México; 2Hospital Regional de Alta Especialidad de Salud Mental, Villahermosa, Tabasco, México; 3Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 4Hospital Psiquiátrico Infantil “Dr. Juan N. Navarro”, Ciudad de México, México; 5División Académica Multidisciplinaria de Jalpa de Méndez, Universidad Juarez Autónoma de Tabasco, Jalpa de Méndez, Tabasco, México; 6División Académica Multidisciplinaria de Comalcalco, Universidad Juarez Autónoma de Tabasco, Comalcalco, Tabasco, México; 7Departamento de Genética Psiquiátrica, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, México&ast;These authors contributed equally to this workCorrespondence: Isela Esther Juárez-Rojop, División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco, Av. Gregorio Méndez 2838-A, Col. Tamulté, Villahermosa, 86100, México, Email [email protected] Humberto Nicolini, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, 86100, México, Email [email protected]: Epigenetic age and inflammatory markers have been proposed as indicators of severity and mortality in patients with COVID-19. Furthermore, they have been associated with the occurrence of neurological symptoms, psychiatric manifestations, and cognitive impairment. Therefore, we aimed to explore the possible associations between epigenetic age, neuropsychiatric manifestations and inflammatory markers (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], monocyte-lymphocyte ratio [MLR], and systemic immune-inflammation index [SII]) in healthcare personnel with post-COVID condition.Patients and Methods: We applied the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) tests to 51 Mexican healthcare workers with post-COVID-19 condition; we also estimated their epigenetic age using the PhenoAge calculator.Results: The participants had a post-COVID condition that lasted a median of 14 months (range: 1– 20). High NLR (> 1.73) had association with mild cognitive impairment by MMSE (p=0.013). Likewise, high MLR (> 0.24) were associated with language domain in MOCA (p=0.046). Low PLR (< 103.9) was also related to delayed recall in MOCA (p=0.040). Regarding comorbidities, hypertension was associated with SII (p=0.007), overweight with PLR (p=0.047) and alcoholism was associated with MLR (p=0.043). Interestingly, we observed associations of low PLR (< 103.9) and low SII (< 1.35) levels with increased duration of post-COVID condition (p=0.027, p=0.031). Likewise, increases in PhenoAge were associated with high levels of SII (OR=1.11, p=0.049), PLR (OR=1.12, p=0.035) and MLR (OR=1.12, p=0.030).Conclusion: We observed neurocognitive changes related to inflammatory markers and increases in epigenetic age in healthcare personnel with post-COVID-19 condition. Future research is required to assess mental and physical health in individuals with post-COVID-19 symptoms.Keywords: post-COVID-19, cognitive manifestation, inflammatory markers, epigenetic ag