Search

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of glutamate decarboxylase autoantibodies (GADA). LADA has intermediate features between type 1 diabetes and type 2 diabetes. In addition, genetic risk factors for both types of diabetes are present in LADA. Nonetheless, evidence about the genetics of LADA in non-European populations is scarce. This study aims to perform a genome-wide association study with a phenome-wide association study of LADA in a southeastern Mexican population. We included 59 patients diagnosed with LADA from a previous study and 3121 individuals without diabetes from the MxGDAR/ENCODAT database. We utilized the GENESIS package in R to perform the genome-wide association study (GWAS) of LADA and PLINK for the phenome-wide association study (PheWAS) of LADA features. Nine polymorphisms reach the nominal association level (1 × 10−5) in the GWAS. The PheWAS showed that rs7305229 is genome-wide and associated with serum GADA levels in our sample (p = 1.84 × 10−8). rs7305229 is located downstream of the FAIM2 gene; previous reports associate FAIM2 variants with childhood obesity, body mass index, body adiposity measures, lymphocyte CD8+ activity, and anti-thyroid peroxidase antibodies. Our findings reveal that rs7305229 affects the GADA levels in patients with LADA from southeastern Mexico. More studies are needed to determine if this risk genotype exists in other populations with LADA.

(1) Background: health care workers, particularly nurses, have been regularly assaulted during the COVID-19 pandemic. Purpose: to evaluate the prevalence and location of assaults against nursing personnel in Latin America, and to determine predictor factors for aggression against nurses. (2) Methods: A cross-sectional online survey was answered by 374 nurses working in health care during the COVID-19 pandemic. The aggression against nurses was estimated using the Victimization Scale. (3) Results: A total of 288 nurses were included in this study. The victimization scale showed that 52.1% of nurses have suffered aggression by the general population during the COVID-19 pandemic. Males were more likely to be attacked than females (p < 0.05). Additionally, males were attacked more frequently on public transport (x2 = 6.72, p = 0.01). The home neighborhood and markets were other locations with a higher risk of being assaulted (OR: 3.39, CI: 1.53–7.50). (4) Conclusions: Our results indicate that nurses in Latin America who work during the COVID-19 pandemic and social isolation have been frequently assaulted by the general public. Males are more frequently attacked than females and the main places of aggression are public transportation, their home neighborhood and supermarkets. Implications for nursing practice: it is necessary to create and implement protocols and guidelines to support nursing personnel during the COVID-19 pandemic. This study was retrospectively registered at the Juarez Autonomous University of Tabasco (103/CIPDACS/2020) on the (08/2020).

Abstract Latent autoimmune diabetes in adults (LADA) has clinical and metabolic features of type 1 and type 2 diabetes. LADA does not have specific features for its diagnosis apart from autoantibody detection; however, these tests are not affordable in clinical settings. In this cross-sectional study, we analyzed clinical criteria, metabolic control, pharmacological treatment, and diabetic complications in two groups of patients with diabetes -LADA and T2D- in order to identify specific characteristic of these clinical entities. Finally, we evaluated if the estimated glucose disposal rate (eGDR) and age at diagnosis of diabetes could be used as a diagnostic criterion for LADA. Demographic, biochemical, clinical and treatment were measured in 377 individuals with diabetes. The diagnostics of LADA were determined using Glutamic acid decarboxylase autoantibodies levels. Chi-square test or t-Student test were used to establish differences between groups. To identify factors associated with LADA, a logistic regression analysis was used. Finally, a ROC curve was plotted to assess the possible variables as diagnostic criteria for LADA. The 377 patients with diabetes were separated into 59 patients with LADA and 318 patients with T2D. Patients with LADA showed lower fasting glucose values, fewer diabetic complications, younger age at diagnosis of diabetes, higher insulin use, and higher eGDR in comparison to patients with T2D. Both groups had a mean BMI classified as overweight. The ROC evaluated the sensitivity and specificity, this analysis indicated that an age younger than 40.5 years and an eGDR value higher than 9.75 mg/kg/min correlated better with LADA. These parameters could be useful to identify patients suspected to have LADA at the first level of medical care in the population of southeastern Mexico and refer them to a second level of care.

The aim of the present study was to evaluate depressive-like, anxiety-like, and perseverative-like behaviors in a binge eating model. Juvenile Wistar rats, using the binge eating model, were compared to caloric restriction, induced stress, and control groups. Rats of the induced stress group presented binge-like behaviors in standard food intake in the second cycle of the experiment when compared to the caloric restriction group and the binge eating model group. Depressive-like behavior was observed in the binge eating model group with longer immobility time (p < 0.001) and less swim time (p < 0.001) in comparison to the control group. Anxiety-like behavior was observed by shorter duration of burying latency in the binge eating model group when compared to the induced stress group (p = 0.04) and a longer duration of burying time when compared to the control group (p = 0.02). We observed perseverative-like behavior by the binge model group, who made more entries to the new arm (p = 0.0004) and spent a longer time in the new arm when compared to the control group (p = 0.0001). Our results show differences in behaviors between the groups of rats studied. These results suggest that calorie restriction–refeeding, along with stress, may lead to depressive-like, anxiety-like, and perseverative-like behavioral changes in male Wistar 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.

Objective: Coronavirus disease 2019 (COVID-19) has impacted mental health worldwide, and suicide can be a serious outcome of this. Thus, suicide characteristics were examined before and during the COVID-19 pandemic in Mexico City. Methods: This is a retrospective study including all Mexico City residents who had a coroner's record with a cause of death of intentional self-harm (ICD-10) from January 2016 to December 2021. Results: From 2016 to 2021, 3636 people committed suicide, of which 2869 were males (78.9%) and 767 females (21.1%). From 2016 to 2019 the suicide rate remained constant (∼6 per 100000) and dramatically increased in 2020 (10.45 per 100,000), to return to the levels of the previous year in 2021 (6.95 per 100000). The suicide rate in 2020 specifically increased from January to June (COVID-19 outbreak) in all age groups. Moreover, every year young people (15–24 years) have the maximum suicide rate and depression was the main suicide etiology. Conclusion: The COVID-19 pandemic outbreak increased the suicide rate, regardless of age, but suicide prevalence was higher in males and young people, regardless of the COVID-19 pandemic. These findings confirm that suicide is a complex and multifactorial problem and will allow the establishment of new guidelines for prevention and care strategies.

Background and Objectives: Poor sleep quality has been frequently observed in individuals with rheumatoid arthritis. In the present study, we analyzed the presence of poor sleep quality in a sample of Mexican individuals with rheumatoid arthritis; then, we compared sociodemographic and clinical characteristics among patients to determine risk factors for poor sleep quality. Materials and Methods: In this cross-sectional study, we included 102 individuals with rheumatoid arthritis from a hospital in Mexico. We evaluated disease activity (DAS28), quality of sleep using the Pittsburgh Sleep Quality Index, and the presence of depression and anxiety with the Hospital Anxiety and Depression Scale. We performed a Chi-square test and a t-test. Then, we performed a logistic regressions model of the associated features in a univariable analysis. Results: Poor sleep quality was observed in 41.75% of the individuals with rheumatoid arthritis. Being married was a proactive factor (OR 0.04, 95% CI 0.1–0.9, p = 0.04), whereas having one’s hips affected or presenting with anxiety and depression was associated with poor sleep quality (OR 4.6, 95% CI 1.2–17.69, p = 0.02). After a multivariate analysis, having anxiety (OR 5.0, 95% CI 1.4–17.7, p < 0.01) and depression (OR 9.2, 95% CI 1.0–8.1, p < 0.01) remained associated with a higher risk of having poor sleep quality. Other clinical characteristics among patients were not significantly different. Conclusions: Our results showed that individuals with rheumatoid arthritis who also presented with depression or anxiety had a higher risk of suffering from poor sleep quality. However, more studies with larger samples are necessary to replicate these results in the Mexican population.

The relationship between the gut-brain-microbiome axis has gained great importance in the study of psychiatric disorders, as it may represent a new target for their treatment. To date, the available literature suggests that the microbiota may influence the pathophysiology of several diseases, including psychosis. The aim of this review is to summarize the clinical and preclinical studies that have evaluated the differences in microbiota as well as the metabolic consequences related to psychosis. Current data suggest that the genera Lactobacillus and Megasphaera are increased in schizophrenia (SZ), as well as alterations in the glutamate-glutamine-GABA cycle, serum levels of tryptophan, kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). There are still very few studies on early-onset psychosis, thus more studies are needed to be able to propose targeted therapies for a point when the disease has just started or has not yet progressed.

Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an increase in gene expression studies has been in development. Through a systematic review, we aimed to find a candidate gene in gene expression studies on postmortem brains of suicide completers. Databases were systematically searched for published studies. We performed an online search using PubMed, Scopus and Web of Science databases to search studies up until May 2023. The terms included were “gene expression”, “expressed genes”, “microarray”, “qRT–PCR”, “brain samples” and “suicide”. Our systematic review included 59 studies covering the analysis of 1450 brain tissues from individuals who died by suicide. The majority of gene expression profiles were obtained of the prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, ventral prefrontal cortex and orbital frontal cortex area. The most studied mRNAs came of genes in glutamate, γ-amino-butyric acid and polyamine systems. mRNAs of genes in the brain-derived neurotrophic factor, tropomyosin-related kinase B (TrkB), HPA axis and chemokine family were also studied. On the other hand, psychiatric comorbidities indicate that suicide by violent death can alter the profile of mRNA expression.

ObjectivesWe aimed to examine the association of TPH1 polymorphisms with the risk of suicide behavior (SB).DesignSystematic review and meta-analysis.MethodAll relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association between TPH1 gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis.ResultsThe meta-analysis for TPH1 A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01–1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05–1.21), homozygous (OR = 1.22, 95%CI 1.06–1.40), heterozygous (OR = 1.21, 95%CI 1.08–1.37) and dominant (OR = 1.21, 95%CI 1.09–1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73–0.97) and dominant (OR = 0.79, 95%CI 0.68–0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12–1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB.ConclusionThis meta-analysis suggests that the A218C polymorphism of TPH1 gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.

BackgroundAbnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been reported in individuals with suicide behavior. The aim of the study was to evaluate cortisol levels in peripheral plasma of individuals with more than one suicide attempt.MethodsCortisol concentrations in peripheral plasma were measured using the ELISA technique. Suicide attempts were evaluated by the Columbia Suicide Severity Rating Scale, while depression was evaluated by the Hamilton Depression Rating Scale.ResultsWe found elevated cortisol levels in the suicide attempt group when compared with healthy controls (F = 7.26, p-value = 0.008), but no statistical differences with the psychiatric diseases group (F = 1.49, p-value = 0.22). Cortisol levels were higher in individuals with depression (F = 8.99, P = 0.004) and in individuals with two or more suicide attempts (F = 13.56, P < 0.001).ConclusionsCortisol levels are increased in individuals who attempt suicide and higher of cortisol concentrations in plasma regard to depression and more attempts of suicide.

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.

Abstract The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p

DNA methylation in genes of the hypothalamic–pituitary–adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were “DNA methylation”, “suicide”, “epigenetics”, “HPA axis” and “suicide behavior”. This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.

This study aimed to explore the role of telomere length in three different diabetes types: latent autoimmune diabetes of adulthood (LADA), latent autoimmune diabetes in the young (LADY), and type 2 diabetes mellitus (T2DM). A total of 115 patients were included, 72 (62.61%) had LADA, 30 (26.09%) had T2DM, and 13 (11.30%) had LADY. Telomere length was measured using real-time Polymerase Chain Reaction. For statistical analysis, we used the ANOVA test, X2 test, and the Mann–Whitney U test. Patients with T2DM had higher BMI compared to LADA and LADY groups, with a BMI average of 31.32 kg/m2 (p = 0.0235). While the LADA group had more patients with comorbidities, there was not a statistically significant difference (p = 0.3164, p = 0.3315, p = 0.3742 for each of the previously mentioned conditions). There was a difference between those patients with T2DM who took metformin plus any other oral antidiabetic agent and those who took metformin plus insulin, the ones who had longer telomeres. LADA patients had shorter telomeres compared to T2DM patients but not LADY patients. Furthermore, T2DM may have longer telomeres thanks to the protective effects of both metformin and insulin, despite the higher BMI in this group.

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.

Glycosylated hemoglobin is used to diagnose type 2 diabetes mellitus and assess metabolic control. Depression itself has been associated with high levels of HbA1c in individuals with T2DM. The association between diabetes and depression suggests the usefulness of determining HbA1c as a biological marker of depressive symptoms. The aim of this study was to determine HbA1c levels in individuals with T2DM with vs. without depression. Additionally, we analyzed the influence of pharmacological treatments, time of evolution, and complications of disease. We performed a literature search in different databases published up to January 2020. A total of 34 articles were included. Our results showed that individuals with T2DM with depression showed increased levels of HbA1c in comparison to individuals with T2DM without depression (d = 0.18, 95% CI: 0.12–0.29, p(Z) < 0.001; I2 = 85.00). We also found that HbA1c levels remained elevated in individuals with T2DM with depression who were taking hypoglycemic drugs (d = 0.20 95% CI: 0.11–0.30, p(Z) < 0.001; I2 = 86.80), in individuals with less than 10 years of evolution (d = 0.17 95% CI: 0.09–0.26, p(Z) = 0.001; I2 = 66.03) and in individuals with complications of the disease (d = 0.17, 95% CI: 0.07–0.26, p(Z) < 0.001; I2 = 58.41). Our results show that HbA1c levels in individuals with T2DM with depression are significantly increased compared to controls with T2DM without depression. Additionally, these levels remained elevated in individuals who were taking hypoglycemic drugs, those with less than 10 years of disease evolution, and those with complications related to diabetes. It is necessary to examine the existence of a diabetes–HbA1c–depression connection.

Recent studies suggest that the endocannabinoid system could play an important role in the physiopathology of obsessive-compulsive disorder (OCD). There are reports of effective treatment with derivatives of tetrahydrocannabinol (THC). The study of the genetic factor associated with psychiatric disorders has made possible an exploration of its contribution to the pharmacological response. However, very little is known about the genetic factor or the prevalence of cannabis use in the Mexican population with OCD. The objective of this study is to compare the prevalence of use and dependence on cannabis in individuals with obsessive-compulsive symptomatology (OCS) with that of individuals with other psychiatric symptoms (psychosis, depression, and anxiety), and to explore the association between genetic risk and use. The study includes a total of 13,130 individuals evaluated in the second stage of the 2016 National Survey of Drug, Alcohol, and Tobacco Use (Encodat 2016), with genetic analysis (polygenic risk scoring) of a subsample of 3,521 individuals. Obsessive symptomatology had a prevalence of 7.2% and compulsive symptomatology a prevalence of 8.6%. The proportion of individuals with OCS who had ever used cannabis was 23.4%, and of those with cannabis dependency was 2.7%, the latter figure higher than that in individuals with other psychiatric symptoms (hypomania, 2.6%; anxiety, 2.8%; depression, 2.3%), except psychosis (5.9%). Individuals with OCS who reported using cannabis had an increased genetic risk for cannabis dependence but not for OCD. We thus cannot know how the increased genetic risk of cannabis dependence in people with OCD is influenced by their pharmacological response to derivatives of THC. The results, however, suggest paths for future studies.

Hand grip strength has been considered as a possible marker for metabolic and psychiatric disease. To date, however, no research has focused on the association between alexithymia and hand grip strength. The objective of the present study was to investigate the correct association between hand grip strength and alexithymia. A cross-sectional study was carried out in Comalcalco, Tabasco, México. A total of 246 individuals were included. Hand grip strength was evaluated in the dominant hand using a Takei® portable digital dynamometer. Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20). Two linear regression models adjusted by confounders were used to determine the association between alexithymia and hand grip strength. The rate for positive alexithymia was 39.0% (n = 94). Individuals with alexithymia showed a weaker hand grip strength than the comparison group (t = 2.4, 244 df, p = 0.01). Individuals with alexithymia had significantly reduced levels of hand grip strength (β = −0.39 ± 0.14; p = 0.006); after additional adjustment for clinical variables, decreased hand grip strength remained (β = 8.00 ± 1.86; p ≤ 0.001). Our results suggest that a decrease in hand grip strength could be associated with alexithymia. This measurement could be useful as a predictive marker for the identification of alexithymia in Mexican individuals who attend outpatient clinics.

Pharmacogenetic analysis has generated translational data that could be applied to guide treatments according to individual genetic variations. However, pharmacogenetic counseling in some mestizo (admixed) populations may require tailoring to different patterns of admixture. The identification and clustering of individuals with related admixture patterns in such populations could help to refine the practice of pharmacogenetic counseling. This study identifies related groups in a highly admixed population-based sample from Mexico, and analyzes the differential distribution of actionable pharmacogenetic variants. A subsample of 1728 individuals from the Mexican Genomic Database for Addiction Research (MxGDAR/Encodat) was analyzed. Genotyping was performed with the commercial PsychArray BeadChip, genome-wide ancestry was estimated using EIGENSOFT, and model-based clustering was applied to defined admixture groups. Actionable pharmacogenetic variants were identified with a query to the Pharmacogenomics Knowledge Base (PharmGKB) database, and functional prediction using the Variant Effect Predictor (VEP). Allele frequencies were compared with chi-square tests and differentiation was estimated by FST. Seven admixture groups were identified in Mexico. Some, like Group 1, Group 4, and Group 5, were found exclusively in certain geographic areas. More than 90% of the individuals, in some groups (Group 1, Group 4 and Group 5) were found in the Central-East and Southeast region of the country. MTRR p.I49M, ABCG2 p.Q141K, CHRNA5 p.D398N, SLCO2B1 rs2851069 show a low degree of differentiation between admixture groups. ANKK1 p.G318R and p.H90R, had the lowest allele frequency of Group 1. The reduction in these alleles reduces the risk of toxicity from anticancer and antihypercholesterolemic drugs. Our analysis identified different admixture patterns and described how they could be used to refine the practice of pharmacogenetic counseling for this admixed 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.

Abstract Background Evidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene‐level association study in Mexican psychiatric individuals diagnosed with suicide attempt. Methods We recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p‐value lower than 1e‐05 was considered as gene‐level significant and a p‐value lower than 1e‐04 was considered as gene‐level nominal significant. Results Our analyses showed that SCARA5 was associated to suicide intent at a gene‐level with statistical significance (p‐value = 1.12e‐6). Other genes were nominally associated with suicide attempt: GHSR (p‐value = 0.0004), RGS10 (p‐value = 5.13e‐5), and STK33 (p‐value = 3.62e‐5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder. Conclusion Our outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.

Suicides and suicidal behavior are major causes of mortality and morbidity in public health and are a global problem. Various authors have proposed changes in lipid metabolism (total cholesterol decrease) as a possible biological marker for suicidal behavior. The objective of this study was to review the studies that have demonstrated a relationship between serum cholesterol levels and suicidal behavior and to describe the possible pathophysiological mechanisms that associate changes in cholesterol concentration and suicidal behavior. Relevant literature related to serum cholesterol levels and suicidal behavior was identified through various database searches. The data from the existing literature present the findings that relate low cholesterol levels and possible pathophysiological mechanisms (neuroinflammation, serotonergic neurotransmission), genes related to cholesterol synthesis, pharmacological treatments that alter lipid metabolism and the possible participation in suicidal behavior. Nevertheless, future research is required to describe how serum cholesterol affects cholesterol metabolism in the CNS to establish and understand the role of cholesterol in suicidal behavior.

Eating disorders are psychiatric disorders characterized by disturbed eating behaviors. They have a complex etiology in which genetic and environmental factors interact. Analyzing gene-environment interactions could help us to identify the mechanisms involved in the etiology of such conditions. For example, comethylation module analysis could detect the small effects of epigenetic interactions, reflecting the influence of environmental factors. We used MethylationEPIC and Psycharray microarrays to determine DNA methylation levels and genotype from 63 teenagers with eating disorders. We identified 11 comethylation modules in WGCNA (Weighted Gene Correlation Network Analysis) and correlated them with single nucleotide polymorphisms (SNP) and clinical features in our subjects. Two comethylation modules correlated with clinical features (BMI and height) in our sample and with SNPs associated with these phenotypes. One of these comethylation modules (yellow) correlated with BMI and rs10494217 polymorphism (associated with waist-hip ratio). Another module (black) was correlated with height, rs9349206, rs11761528, and rs17726787 SNPs; these polymorphisms were associated with height in previous GWAS. Our data suggest that genetic variations could alter epigenetics, and that these perturbations could be reflected as variations in clinical features.

Background/Aim: Obesity in adolescents is increasing; as such, the aim of this study was to determine the prevalence of obesity in Mexican adolescents and examine its possible association with hours of sleep. Methods: A school-based cross-sectional study was carried out. This study included 863 adolescents aged between 11 and 16 years. The prevalence of obesity was estimated using the body mass index (BMI). The duration of sleep (and other information) was assessed by a self-reported questionnaire. The Cochran–Mantel–Hansel test for categorical variables and a general linear model for continuous variables were used to evaluate the interaction effect of BMI and sex with respect to sleeping and assessed activity conditions. Results: It was found that 47.6% of the adolescents were overweight/obese. Men were more frequently overweight/obese than women (52.6% vs. 41.8%, p = 0.002). Moreover, overweight/obese adolescents were younger and spent fewer daily hours watching television (p < 0.05). Men practiced sports more hours per week than women (p = 0.04). However, women spent more daily time on the internet (p = 0.05), and overweight/obese adolescent women slept fewer hours than overweight/obese men and adolescents with normal weight (p = 0.008). Conclusions: The development of strategies for the prevention of overweight/obesity and the improvement of sleep duration should include a gender perspective to improve health habits in Mexican adolescents.

The identification and characterization of pharmacogenetic variants in Latin American populations is still an ongoing endeavor. Here, we investigated SNVs on genes listed by the Pharmacogenomics Knowledge Base in 1284 Mestizos and 94 Natives from Mexico. Five institutional cohorts with NGS data were retrieved from different research projects at INMEGEN, sequencing files were filtered for 55 pharmacogenes present in all cohorts to identify novel and known variation. Bioinformatic tools VEP, PROVEAN, and FATHMM were used to assess, in silico, the functional impact of this variation. Next, we focused on 17 genes with actionable variants that have been clinically implemented. Allele frequencies were compared with major continental groups and differences discussed in the scope of a pharmacogenomic impact. We observed a wide genetic variability for known and novel SNVs, the largest variation was on UGT1A > ACE > COMT > ABCB1 and the lowest on APOE and NAT2. Although with allele frequencies around 1%, novel variation was observed in 16 of 17 PGKB genes. In Natives we identified 59 variants and 58 in Mestizos. Several genes did not show novel variation, on CYP2B6, CYP2D6, and CYP3A4 in Natives; and APOE, UGT1A, and VKORC1 in Mestizos. Similarities in allele frequency, comparing major continental groups for VIP pharmacogenes, hint towards a comparable PGx for drugs metabolized by UGT1A1, DPYD, ABCB1, CBR3, COMT, and TPMT; in contrast to variants on CYP3A5 and CYP2B6 for which significant MAF differences were identified. Our observations offer some discernment into the extent of pharmacogenetic variation registered up-to-date in Mexicans and contribute to quantitatively dissect actionable pharmacogenetic variants in Natives and Mestizos.

Abstract Introduction The 5‐HTR2A gene has been implicated as candidate gene for eating disorders. The aim of the present study was to analyze the association of rs6311 and rs6313 polymorphisms of 5‐HTR2A gene with eating disorders in Mexican population, and to evaluate if the polymorphisms of 5‐HTR2A gene were associated with comorbidities in eating behavior. Methods We conducted a case–control analysis with 460 subjects. We included 168 patients with eating disorders and 292 controls; two polymorphisms of 5‐HTR2A gene were genotyped. We assessed the association by allele, genotype, and inheritance models. Psychiatric comorbidities were analyzed by genotype in patients with eating disorders. Results We found an association between rs6311 and eating disorders in a Mexican population by allele (OR = 8.09; 95% CI = 5.99–11.03; p = 2.2e‐16) and genotype (OR = 76.14; 95% CI = 35.61–177.18; p = 2.2e‐16). Individuals who carried GG genotype showed increased risk for suicide attempted (OR = 2.14; CI = 1.10–4.26; p = 0.035) as comorbidity associated with eating disorders. No positive associations were observed for rs6313 polymorphism. Conclusion Our results showed an association of rs6311 (A1438G) polymorphism of 5‐HTR2A gene with eating disorders, and these polymorphic variants could increase the risk of psychiatric comorbidities. However, more studies are required to replicate the results and to reach to a conclusive association between eating disorders and rs6311.

Abstract Introduction Several studies indicate that polygenic obesity is linked to fat‐mass and obesity‐associated (FTO) genetic variants. Nevertheless, the link between variants in FTO and mental disorders has been barely explored. The present work aims to determine whether FTO genetic variants are associated with bipolar disorder and obesity, and to perform an in silico prediction of variant‐dependent functional impact on the developing brain transcriptome. Methods Four hundred and forty‐six Mexican mestizos were included in a genetic association analysis. SNP‐sequence kernel association test and linear mixed models were implemented for genetic association assessment. For functional impact prediction, we analyzed the mapping of regulatory elements, the modification of binding sites of transcription factors and the expression of transcription factors in the brain developing transcriptome, searching on different databases. Results In the set‐based analysis, we found different associated regions to BD (bipolar disorder) and obesity. The promoter flanking region of FTO intron 1 was associated with differential effects on BMI, while intron 2 of RPGRIP1L and FTO upstream regions were associated with BD. The prediction analysis showed that FTO BD‐associated variants disturb binding sites of SP1 and SP2; obesity‐associated variants, on the other hand, disturb binding sites of FOXP1, which are transcription factors highly expressed during prenatal development stages of the brain. Conclusion Our results suggest a possible effect of FTO variants on neurodevelopment in obesity and bipolar disorder, which gives new insights into the molecular mechanism underlying this association.

Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN. A total of 46 individuals were analyzed using the Infinium Methylation EPIC array. We found 11 differentially methylated sites between BED- and BN-diagnosed individuals, with genome-wide significance. Most of the associations were found in genes related to metabolic processes (ST3GAL4, PRKAG2, and FRK), which are hypomethylated genes in BED. Cg04781532, located in the body of the PRKAG2 gene (protein kinase AMP-activated non-catalytic subunit gamma 2), was hypomethylated in individuals with BED. Agonists of PRKAG2, which is the subunit of AMPK (AMP-activated protein kinase), are proposed to treat obesity, BED, and BN. The present study contributes important insights into the effect that BED could have on PRKAG2 activation.

The aim of this study was to evaluate the effects of non-nutritive sweeteners (NNS) consumption on energy intake, body weight and postprandial glycemia in healthy and with altered glycemic response rats. Animals on normal diet (ND) or high-fat diet (HFD) were divided to receive NNS (sucralose, aspartame, stevia, rebaudioside A) or nutritive sweeteners (glucose, sucrose) for 8 weeks. The NNS were administered at doses equivalent to the human acceptable daily intake (ADI). A test using rapidly digestible starch was performed before and after treatments to estimate glycemic response. No effects of NNS consumption were observed on energy intake or body weight. Sucrose provoked an increased fluid consumption, however, energy intake, and weight gain were not altered. In ND, no effects of NNS on glycemic response were observed. In HFD, the glycemic response was increased after sucralose and stevia when only the final tolerance test was considered, however, after including the baseline test, these results were no longer significant compared to glucose. These findings provide further evidence suggesting that at the recommended doses, NNS do not alter feeding behavior, body weight or glycemic tolerance in healthy and with altered glycemic rats.

Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to be enriched in BD-PRS and was associated with the CLZ metabolic ratio. Such interplay supports the use of CLZ as a mood stabilizer and not just as an antipsychotic. Future studies with larger sample sizes should be pursued to confirm the findings of this study.