Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts.

Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e-5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e-8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation's impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.

A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.

BACKGROUND: Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes. METHODS: We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N ≤ 2,619,939), Latin American (N ≤ 446,646) and African American (N ≤ 146,776) populations to uncover new and perhaps unexpected associations. These SNPs have been consistently implicated by both candidate gene studies and genome-wide association studies of alcohol-related behaviours but have not been investigated in detail for other relevant phenotypes in a hypothesis-free approach in such a large cohort of multiple ancestries. To provide insight into potential causal effects of alcohol consumption on the outcomes significant in the PheWAS, we performed univariable two-sample and one-sample Mendelian randomisation (MR) analyses. FINDINGS: The minor allele rs1229984-T, which is protective against alcohol behaviours, showed the highest number of PheWAS associations across the three cohorts (N = 232, European; N = 29, Latin American; N = 7, African American). rs1229984-T influenced multiple domains of health. We replicated associations with alcohol-related behaviours, mental and sleep conditions, and cardio-metabolic health. We also found associations with understudied traits related to neurological (migraines, epilepsy), immune (allergies), musculoskeletal (fibromyalgia), and reproductive health (preeclampsia). MR analyses identified evidence of causal effects of alcohol consumption on liability for 35 of these outcomes in the European cohort. INTERPRETATION: Our work demonstrates that polymorphisms in genes encoding alcohol metabolising enzymes affect multiple domains of health beyond alcohol-related behaviours. Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine. FUNDING: MVJ, NCK, SBB, SSR and AAP were supported by T32IR5226 and 28IR-0070. SSR was also supported by NIDA DP1DA054394. NCK and RBC were also supported by R25MH081482. ASH was supported by funds from NIAAA K01AA030083. JLMO was supported by VA 1IK2CX002095. JLMO and JJMM were also supported by NIDA R21DA050160. JJMM was also supported by the Kavli Postdoctoral Award for Academic Diversity. EGA was supported by K01MH121659 from the NIMH/NIH, the Caroline Wiess Law Fund for Research in Molecular Medicine and the ARCO Foundation Young Teacher-Investigator Fund at Baylor College of Medicine. MSA was supported by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus (FSE+) (P19/01224, PI22/00464 and CP22/00128).

Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder.

Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5 hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5 mC and 5 hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC). Methods: Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5 mC and 5 hmC at the genome-wide level. Differential 5 mC and 5 hmC were evaluated using the methylKit R package and significance was set at false discovery rate < 0.05 and differential methylation > 2. Functional enrichment analyses were performed, and gene-level convergence was evaluated in an independent dataset that assessed 5 mC and 5 hmC of AUD in bulk cortical tissue. Results: We identified 417 5 mC and 363 5hmC significant differential CpG sites associated with AUD, with 59% in gene promoters. Some of the identified genes have been previously implicated in alcohol consumption, including SYK, DNMT3A for 5 mC, GAD1, DLX1, DLX2, for 5 hmC and GATA4 in both. Convergence with a previous AUD 5 mC and 5 hmC study was observed for 28 genes. We also identified 5 and 35 differential regions for 5 mC and 5 hmC, respectively. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5 mC genes. Discussion: This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD, identifying both previously reported and potentially novel gene associations with AUD. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.

Differential Alterations of Expression of the Serotoninergic System Genes and Mood-Related Behavior by Consumption of Aspartame or Potassium Acesulfame in Rats.

The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression.

Neuronal-specific methylome and hydroxymethylome analysis reveal replicated and novel loci associated with alcohol use disorder.

Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5mC and 5hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC). Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5mC and 5hmC at the genome-wide level. Differential 5mC and 5hmC were evaluated using the methylKit R package and significance was set at false discovery rate <0.05 and differential methylation >2. Functional enrichment analyses were performed and replication was evaluated replication in an independent dataset that assessed 5mC and 5hmC of AUD in bulk cortical tissue. We identified 417 5mC and 363 5hmC genome-wide significant differential CpG sites associated with AUD, with 59% in gene promoters. We also identified genes previously implicated in alcohol consumption, such as SYK, CHRM2, DNMT3A, and GATA4, for 5mC and GATA4, and GAD1, GATA4, DLX1 for 5hmC. Replication was observed for 28 CpG sites from a previous AUD 5mC and 5hmC study, including FOXP1. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5mC genes. This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD. We replicated previous findings and identified novel associations with AUD for both 5mC and 5hmC marks within the OFC. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review.

Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex.

Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

Association between Genetic Variants of CELSR2-PSRC1-SORT1 and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13-1.26, dominant OR 1.22, 95% CI 1.06-1.39, recessive OR 1.23, 95% CI 1.15-1.32), rs646776 (allelic OR 1.46, 95% CI 1.17-1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the CELSR2-PSRC1-SORT1 cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease.

The Prevalence of Symptomatology and Risk Factors in Mental Health in Mexico: The 2016-17 ENCODAT Cohort.

There is little recent information about the prevalence of symptomatology of mental health disorders in representative population samples in Mexico. To determine the prevalence of mental health symptoms in Mexico and its comorbidity with tobacco, alcohol, and drug use disorder (SUD), we used the 2016-17 National Survey of Drug, Alcohol, and Tobacco Use (Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco, ENCODAT 2016-2017). The data were collected from households using a cross-sectional, stratified, multistage design, with a confidence level of 90% and a response rate of 73.6%. The final sample included 56,877 completed interviews of individuals aged 12-65, with a subsample of 13,130 who answered the section on mental health. Symptoms of mania and hypomania (7.9%), depression (6.4%), and post-traumatic stress (5.7%) were the three main problems reported. Of this subsample, 56.7% reported using a legal or illegal drug without SUD, 5.4% reported SUD at one time on alcohol, 0.8% on tobacco, and 1.3% on medical or illegal drugs, 15.9% reported symptoms related to mental health, and 2.9% comorbidity. The prevalence found is consistent with those reported in previous studies, except for an increase in post-traumatic stress, which is consistent with the country's increase in trauma.

Effect of risperidone on serum IL-6 levels in individuals with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Risperidone has been significant correlated with a direct effect of interleukin-6 (IL-6) levels in patients with schizophrenia. This fact allows the opportunity to link the probable immunomodulatory effect of antipsychotic medication. Specially, a proper functioning of IL-6 pathway plays a potential role in the treatment or development of schizophrenia. OBJECTIVE: Our primary aim was to perform a systematic review and meta-analysis to determine the effect of risperidone on IL-6 levels in individuals with schizophrenia. METHODS: Studies were identified through a systematic search using PubMed, Scopus, and Web of Science databases. The articles found were subjected to the inclusion and exclusion criteria; then, the mean and standardised differences were extracted to calculate the standardised mean differences using the CMA software. RESULTS: IL-6 levels in individuals with schizophrenia were compared before and after receiving risperidone as treatment. Increased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone (point estimate 0.249, lower limit 0.042, upper limit 0.455, p-value 0.018). In the Asian population sub-analysis, no statistically significant differences were observed (point estimate 0.103, lower limit -0.187, upper limit 0.215, p value 0.890). When we compared individuals with schizophrenia to the control groups, a significant increase of IL-6 levels was observed in the group with schizophrenia (point estimate 0.248, lower limit 0.024, upper limit 0.472, p-value 0.30). CONCLUSIONS: Risperidone appears to play an important role in IL-6 levels in schizophrenia. Potential implications of increased IL-6 levels in people with schizophrenia should be considered in future studies.KEY POINTSIncreased levels of IL-6 levels were observed in individuals with schizophrenia who received risperidone.Risperidone appears to play an important role in IL-6 levels in schizophrenia.This study could serve for future research focussed on IL-6.

Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes.

Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein-protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes.

The role of alcohol intake in the pharmacogenetics of treatment with clozapine.

Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated with the concomitant use of alcohol. Additionally, pharmacogenetic studies have explored the influence of several genetic variants in CYP450, receptors and transporters involved in the interindividual response to CLZ. Herein, we systematically review the current multiomics knowledge behind the interaction between CLZ and alcohol intake, and how its concomitant use might modulate the pharmacogenetics. CYP1A2*1F, *1C and other alleles not yet discovered could support a precision medicine approach for better therapeutic effects and fewer CLZ ADRs. CLZ monitoring systems should be amended and include alcohol intake to protect patients from severe CLZ ADRs.

Las percepciones de crianza materna podrían influenciar las conductas autolesivas en adolescentes con diagnóstico de trastornos de la conducta alimentaria / Memories of maternal upbringing could influence self-injurious behaviors in adolescents with diagnosis of eating disorders

RESUMEN Objetivo : Explorar las percepciones de crianza parental en adolescentes diagnosticados con algún trastorno de la conducta alimentaria, e identificar posibles diferencias con alteraciones de la conducta alimentaria y conductas autolesivas. Material y métodos : Un total de 45 adolescentes con algún tipo de trastorno de la conducta alimentaria (TCA) (11 diagnosticados con anorexia nervosa, 23 con bulimia nervosa y 11 con trastorno "por atracón"), pacientes en áreas de consulta externa y hospitalización del Hospital Psiquiátrico Infantil Juan N. Navarro fueron sistemáticamente estudiados. Resultados : Se encontró que cuánto mayores las percepciones de favoritismo (r = 0,41, valor p = 0,005) o rechazo (r = 0,36, valor p = 0,016) del padre, mayores fueron también los puntajes en la Escala de Actitudes Alimentarias. Se encontraron asimismo diferencias en la dimensión de calidez de la madre, entre los adolescentes que presentaron autolesiones (media = 39,6, d.e = 11,3) comparados con aquéllos que no las presentaron (media = 47,4, d.e = 8.8) (t = -2,6, valor p = 0,015). Conclusiones : Los adolescentes con diagnóstico de TCA presentaron diferencias en la percepción de crianza parental, factor que puede influenciar decisivamente la manifestación de otras conductas psicopatológicas.

SUMMARY Objective : To explore the perceived parental rearing behavior in adolescents diagnosed with an eating disorder, and to identify eventual differences with altered eating and self-injurious behaviors. Material and methods : A total of 45 adolescents diagnosed with some eating disorder (11 diagnosed with anorexia nervosa, 23 with bulimia nervosa and 11 with binge eating disorder), recruited from the outpatient and hospitalization areas of the Juan N Navarro Children's Psychiatric Hospital, were included. Results : It was found that the greater the memories of favoritism (r = 0.41, p-value = 0.005) or rejection (r = 0.36, p-value = 0.016) by the father, the higher the scores ​​on the Eating Attitude Scale. Differences were also found in the mother's warmth dimension, between the adolescents who presented self-injuries (mean = 39.6, de = 11.3) and those who did not present them (mean = 47.4, de = 8.8) (t = -2.6, value p = 0.015). Conclusions : Adolescents with a diagnosis of eating disorders presented differences in their perception of parental rearing, a factor that may decisively influence the manifestation of other psychopathological behaviors.

Genome-Wide Analysis of Disordered Eating Behavior in the Mexican Population.

Alterations in eating behavior characterized eating disorders (ED). The genetic factors shared between ED diagnoses have been underexplored. The present study performed a genome-wide association study in individuals with disordered eating behaviors in the Mexican population, blood methylation quantitative trait loci (blood-meQTL), summary data-based Mendelian randomization (SMR) analysis, and in silico function prediction by different algorithms. The analysis included a total of 1803 individuals. We performed a genome-wide association study and blood-meQTL analysis by logistic and linear regression. In addition, we analyzed in silico functional variant prediction, phenome-wide, and multi-tissue expression quantitative trait loci. The genome-wide association study identified 44 single-nucleotide polymorphisms (SNP) associated at a nominal value and seven blood-meQTL at a genome-wide threshold. The SNPs show enrichment in genome-wide associations of the metabolic and immunologic domains. In the in silico analysis, the SNP rs10419198 (p-value = 4.85 × 10-5) located on an enhancer mark could change the expression of PRR12 in blood, adipocytes, and brain areas that regulate food intake. Additionally, we found an association of DNA methylation levels of SETBP1 (p-value = 6.76 × 10-4) and SEMG1 (p-value = 5.73 × 10-4) by SMR analysis. The present study supports the previous associations of genetic variation in the metabolic domain with ED.

Fluoxetine modulates the pro-inflammatory process of IL-6, IL-1ß and TNF-α levels in individuals with depression: a systematic review and meta-analysis.

Clinical evidence suggests that inflammation is a key factor to understand the causes of depressive symptoms. Fluoxetine is one of the main first-line medications used for depression, and it is hypothesized that it participates in the decrease of pro-inflammatory cytokines. Hence, our aim was to perform a meta-analysis and systematic review to understand the interaction of fluoxetine in the IL-1ß, IL-6 and TNF-α inflammatory process. Studies identified in PubMed and Scopus databases were used to perform a meta-analysis via the Comprehensive software. Standardized mean difference (SMD) was used as a summary statistic. The analysis included a total of 292 individuals with major depressive disorder who received fluoxetine for a period longer than 6 weeks; additionally, IL-1ß, IL-6 or TNF-α levels were measured at the end of the antidepressant treatment. The findings were significant revealed decreased levels of the cytokines studied. In conclusion, the pooled data suggest that fluoxetine treatment improved depressive symptomatology by the modulation of pro-inflammatory process such as IL-1ß, IL-6 or TNF-α.

Mental Health Problems Due to Social Isolation During the COVID-19 Pandemic in a Mexican Population.

Introduction: Social isolation due to the COVID-19 pandemic has been identified as a risk factor of several mental disorders. Therefore, the present work aimed to evaluate the effect of social isolation experienced during the COVID-19 pandemic on the mental health of a Mexican population. Materials and Methods: A cross-sectional online survey was conducted in individuals of 18 years of age and over. The questioner was structured to identify onset or worsening of psychiatric symptoms due to social isolation by COVID-19. The survey included changes in eating habits, changes in personal hygiene habits, the starting the use or increased the use of psychoactive substances, symptoms of depression or post-traumatic stress. Results: A total of 1,011 individuals were included in the analysis. The majority were women (68.84%). Changes in eating habits were reported in 38.51% of the participants, 67.80% reported having their physical self-perception distorted or having started a low-calorie diet. Regarding symptoms of depression, 46.10% participants indicated to have at least one depressive symptom, and 4.46% reported suicidal ideation during social isolation. Interestingly, 6.09% of individuals reported that they used to have depressive symptoms prior the COVID-19 pandemic and those symptoms decreased due to social isolation. Additionally, 2.27% of individuals presented symptoms of post-traumatic stress due to the possibility of getting COVID-19. Conclusions: In this work we identified how social isolation has impacted the mental health of the Mexican population. We observed that practically all the symptoms evaluated were affected during isolation, such as personal hygiene and eating habits. Depression and suicidal ideation were the ones that increased the most in the general population, while in individuals who had symptoms of depression before isolation, these symptoms decreased during social isolation.

Years of Schooling Could Reduce Epigenetic Aging: A Study of a Mexican Cohort.

Adverse conditions in early life, including environmental, biological and social influences, are risk factors for ill-health during aging and the onset of age-related disorders. In this context, the recent field of social epigenetics offers a valuable method for establishing the relationships among them However, current clinical studies on environmental changes and lifespan disorders are limited. In this sense, the Tlaltizapan (Mexico) cohort, who 52 years ago was exposed to infant malnutrition, low income and poor hygiene conditions, represents a vital source for exploring such factors. Therefore, in the present study, 52 years later, we aimed to explore differences in clinical/biochemical/anthropometric and epigenetic (DNA methylation) variables between individuals from such a cohort, in comparison with an urban-raised sample. Interestingly, only cholesterol levels showed significant differences between the cohorts. On the other hand, individuals from the Tlaltizapan cohort with more years of schooling had a lower epigenetic age in the Horvath (p-value = 0.0225) and PhenoAge (p-value = 0.0353) clocks, compared to those with lower-level schooling. Our analysis indicates 12 differentially methylated sites associated with the PI3-Akt signaling pathway and galactose metabolism in individuals with different durations of schooling. In conclusion, our results suggest that longer durations of schooling could promote DNA methylation changes that may reduce epigenetic age; nevertheless, further studies are needed.

[The presence of a psychiatric diagnosis could alter the epigenetic clock in monozygotic twins]. / La presencia de algún trastorno psiquiátrico podría alterar el reloj epigenético en gemelos monocigóticos.

BACKGROUND: The acceleration of the epigenetic clock has been associated with a reduction in life expectancy. Individuals diagnosed with a psychiatric disorder have a reduction in life expectancy, and some studies have correlated it with accelerated aging. OBJECTIVE: The present study aims to explore whether the presence of any psychiatric disorder could accelerate the epigenetic clock in monozygotic twins. METHODS: A total of 15 pairs of monozygotic twins were included. Epigenetic age in peripheral blood cells was estimated by previously published algorithms, using the 450K Beadchip microarray. RESULTS: We found that in twins with a diagnosis of a psychiatric disorder, the epigenetic clock could increase compared to their twin without a psychiatric disorder. DISCUSSION AND CONCLUSION: The presence of some psychiatric disorder could accelerate the epigenetic clock in homozygous twins, but studies with larger samples are required to clarify this relationship.