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BackgroundSuicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels and altered brain transport mechanisms. Despite Zn’s crucial role in pituitary function and its involvement in suicidal behavior, information on pituitary Zn in suicide is scarce. Tumor cells modify Zn dynamics in tissues, and a previous report suggests microadenomas in the anterior pituitary as a risk factor for suicide.MethodsHistopathological analysis with hematoxylin-eosin stain and histochemical techniques to assess Zn homeostasis were carried out on anterior pituitary postmortem samples from 14 suicide completers and 9 non-suicidal cases.ResultsPituitary microadenomas were identified in 35% of suicide cases and none in the non-suicidal cases. Furthermore, compartmentalized Zn (detected via dithizone reactivity), but not free Zn levels (detected via zinquin reactivity), was lower in the suicide cases compared to the non-suicidal group.ConclusionThis is the first report of a potential association between disrupted Zn homeostasis and microadenomas in the anterior pituitary as a feature in suicide and provides critical insights for future neuroendocrine Zn-related research.

(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).

Background: Alexithymia is a trait involving difficulties in processing emotions. Genetic association studies have investigated candidate genes involved in alexithymia’s pathogenesis. Therefore, the aim of the present study was to perform a systematic review of the genetic background associated with alexithymia. Methods: A systematic review of genetic studies of people with alexithymia was conducted. Electronic databases including PubMed, Scopus, and Web of Science were searched for the study purpose. We used the words “Alexithymia”, “gene”, “genetics”, “variants”, and “biomarkers”. The present systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We found only candidate gene studies. A total of seventeen studies met the eligibility criteria, which comprised 22,361 individuals. The candidate genes associated with alexithymia were the serotoninergic pathway genes solute carrier family 6 member 4 (SLC6A4), serotonin 1A receptor (HTR1A), and serotonin 1A receptor (HTR2A); the neurotransmitter metabolism genes dopamine receptor D2 (DRD2), ankyrin repeat and kinase domain containing 1 (ANKK1), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and oxytocin receptor (OXTR); and other pathway genes, vitamin D-binding protein (VDBP), tumor protein P53 regulated apoptosis inducing protein 1 (TP53AIP1), Rho GTPase Activating Protein 32 (ARHGAP32), and transmembrane protein 88B (TMEM88B). Conclusion: The results of this study showed that only case–control gene studies have been performed in alexithymia. On the basis of our findings, the majority of alexithymia genes and polymorphisms in this study belong to the serotoninergic pathway and neurotransmitter metabolism genes. These data suggest a role of serotoninergic neurotransmission in alexithymia. Nevertheless, more and future research is required to learn about the role of these genes in alexithymia.

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.

The etiology of Autism Spectrum Disorders (ASD) is a result of the interaction between genes and the environment. The study of epigenetic factors that affect gene expression, such as DNA methylation, has become an important area of research in ASD. In recent years, there has been an increasing body of evidence pointing to epigenetic mechanisms that influence brain development, as in the case of ASD, when gene methylation dysregulation is present. Our analysis revealed 853 differentially methylated CpG in ASD patients, affecting 509 genes across the genome. Enrichment analysis showed five related diseases, including autistic disorder and mental disorders, which are particularly significant. In this work, we identified 64 genes that were previously reported in the SFARI gene database, classified according to their impact index. Additionally, we identified new genes that have not been previously reported as candidates with differences in the methylation patterns of Mexican children with ASD.

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.

Obsessive-compulsive disorder (OCD) is frequent and often disabling. Yet, correct diagnosis and appropriate treatment implementation are usually delayed, with undesirable consequences. In this paper we review the rationale for early intervention in OCD and provide recommendations for early intervention services. Two scenarios are discussed, i.e., subclinical (prodromal) obsessive-compulsive symptoms (OCS) and full-blown OCD. Although the typical patient with OCD reports a long history of subclinical OCS, longitudinal studies suggest most individuals with OCS in the community do not convert to full-blown OCD. Thus, research on “at risk” phenotypes for OCD and how they should incorporate different risk factors (e.g., polygenic risk scores) are badly needed. For this specific scenario, preventative treatments that are cheap, well tolerated and highly scalable (e.g., lifestyle interventions) are of major interest. On the other hand, increasing evidence suggests OCD to be a progressive disorder and the severity and duration of illness to be associated with both biological changes and increased clinical complexity, including greater number of physical and psychiatric comorbidities, increased family accommodation and worse treatment response. Therefore, prompt identification and early treatment implementation for full-blown OCD are also critical for ethical, clinical and therapeutic reasons. Based on the existing findings, we argue that, regardless of focusing on subclinical OCS or clinical OCD, early intervention services need to target a childhood age group. In addition to delivering well established treatments to people with full-blown OCD early on their illness, early intervention services also need to provide psychoeducation for patients, families and teachers.

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.

Introduction: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD. Methods: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS). Results: Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p

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.

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.

Objective: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. Methods: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. Results: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. Conclusions: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.

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.

Objetivo: Evaluar mediante resonancia magnética (RM) la progresión de la lesión en el modelo de esquizofrenia de lesión del núcleo del hipocampo ventral (LNHV). Método: Se realizaron RM en ratas Wistar macho, desde los 8 días posnatales hasta los 139 días, en animales con LNHV y sin lesión (sham). Las RM se realizaron con un equipo Variant de 7 T. Los datos se analizaron con el software Amira para un análisis de morfometría basada en vóxels. Resultados: Observamos hiperseñales con un realce significativo en las estructuras analizadas en el grupo con LNHV, y mayor volumen en los ventrículos laterales, presentando un mayor tamaño de la lesión el día PD96 y significativamente reducido en el día PD139. Conclusiones: Encontramos un reacomodo celular durante la progresión de la lesión, lo cual podría ser efecto de la activación de las células inmunitarias.

Autism Spectrum Disorders (ASD) comprise a group of heterogeneous and complex neurodevelopmental disorders. Genetic and environmental factors contribute to ASD etiology. DNA methylation is particularly relevant for ASD due to its mediating role in the complex interaction between genotype and environment and has been implicated in ASD pathophysiology. The lack of diversity in DNA methylation studies in ASD individuals is remarkable. Since genetic and environmental factors are likely to vary across populations, the study of underrepresented populations is necessary to understand the molecular alterations involved in ASD and the risk factors underlying these changes. This study explored genome-wide differences in DNA methylation patterns in buccal epithelium cells between Mexican ASD patients (n = 27) and age-matched typically developing (TD: n = 15) children. DNA methylation profiles were evaluated with the Illumina 450k array. We evaluated the interaction between sex and ASD and found a differentially methylated region (DMR) over the 5′UTR region of ZFP57 and one of its targets, RASGRF2. These results match previous findings in brain tissue, which may indicate that ZFP57 could be used as a proxy for DNA methylation in different tissues. This is the first study performed in a Mexican, and subsequently, Latin American, population that evaluates DNA methylation in ASD patients.

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.

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.

La pandemia que venimos sufriendo desde este año 2020, a causa de la enfermedad por coronavirus SARS-CoV-2 (COVID-19), ha marcado nuestras vidas y ha modificado nuestras conductas, nuestras percepciones y el entorno.

Late-onset Alzheimer's Disease (LOAD) is the most common form of dementia in the elderly. Genome-wide association studies (GWAS) for LOAD have open new avenues to identify genetic causes and to provide diagnostic tools for early detection. Although several predictive models have been proposed using the few detected GWAS markers, there is still a need for improvement and identification of potential markers. Commonly, polygenic risk scores are being used for prediction. Nevertheless, other methods to generate predictive models have been suggested. In this research, we compared three machine learning methods that have been proved to construct powerful predictive models (genetic algorithms, LASSO, and step-wise) and propose the inclusion of markers from misclassified samples to improve overall prediction accuracy. Our results show that the addition of markers from an initial model plus the markers of the model fitted to misclassified samples improves the area under the receiving operative curve by around 5%, reaching ~0.84, which is highly competitive using only genetic information. The computational strategy used here can help to devise better methods to improve classification models for AD. Our results could have a positive impact on the early diagnosis of Alzheimer's disease.

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.

Abstract Background Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present study aims to evaluate the relationship between APOE gene alleles and the lipid profile in a Mexican Amerindian (MA) population. Methods This study included 1997 MA individuals of different ethnicities distributed throughout different states of Mexico. All individuals underwent anthropometric measurements as well as laboratory tests including fasting glucose (FG), total cholesterol (TC), triglycerides, low‐density lipoprotein cholesterol (LDL‐C), and high‐density lipoprotein cholesterol (HDL‐C). TaqMan® probe genotyping assays were used to genotype APOE. The Kruskal–Wallis test was performed to determine the correlation between APOE gene alleles and genotypes and the biochemical variables measured. Results Among the biochemical variables analyzed, only the HDL‐C and LDL‐C levels showed statistical differences (p‐value E3 > E4). This relationship was inversed for LDL‐C levels (E2

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.

Background: Suicide behavior (SB) has been highly associated with the response to stress and the hypothalamic–pituitary–adrenal (HPA) axis. The aim of this study was to summarize the results obtained in genetic studies that analyzed the HPA axis—stress pathway and SB through a systematic review. Methods: We performed an online search in PubMed, EBSCO, Web of Science, Scopus, and PsycoInfo databases up to May 2021. We followed the PRISMA guidelines for systematic reviews. We included case-control and expression studies that provided data on mRNA expression and single-nucleotide polymorphisms of genes associated with SB. Results: A total of 21,926 individuals participated across 41 studies (not repeats); 34 studies provided data on single-nucleotide polymorphisms in 21,284 participants and 11 studies reported data on mRNA expression in 1034 participants. Ten genes were identified: FKBP5, CRH, CRHBP, CRHR1, CRHR2, NR3C1, NR3C2, SKA2, MC2R, and POMC. Conclusions: Our findings suggest that key stress pathway genes are significantly associated with SB and show potential as biomarkers for SB.

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.

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.

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.

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.

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.

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.

Objective: To analyze sex differences in demographic and clinical characteristics of individuals who died by suicide in Mexico City.Method: Statistical analysis of residents of Mexico City whose cause of death was suicide, during two years period from January 2014 to December 2015, with a coroner's report. Suicide mortality rates were calculated by age, sex, and location within the city. The Chi-squared test was used to assess statistical differences.Results: From January 2014 to December 2015, 990 residents of Mexico City died by suicide (men: 78.28%, women: 21.72%). Among males, the highest mortality rates were among the groups of 20–24 and 75–79 years old, whereas in women, the group with the highest mortality rate was 15 to 19 years old. 74% of the sample used hanging as suicide method. However, men had higher rates of a positive result in the toxicology test (40%) (p < 0.05). There was no concordance between male and female suicide by city jurisdictions.Conclusion: Our results provide evidence that the characteristics of Mexico City's residents who committed suicide had significant sex-related differences, including where they used to live. Understanding the contributory factors associated with completed suicide is essential for the development of effective preventive strategies.

The integration of different sources of biological information about what defines a behavioral phenotype is difficult to unify in an entity that reflects the arithmetic sum of its individual parts. In this sense, the challenge of Systems Biology for understanding the “psychiatric phenotype” is to provide an improved vision of the shape of the phenotype as it is visualized by “Gestalt” psychology, whose fundamental axiom is that the observed phenotype (behavior or mental disorder) will be the result of the integrative composition of every part. Therefore, we propose the term “Gestaltomics” as a term from Systems Biology to integrate data coming from different sources of information (such as the genome, transcriptome, proteome, epigenome, metabolome, phenome, and microbiome). In addition to this biological complexity, the mind is integrated through multiple brain functions that receive and process complex information through channels and perception networks (i.e., sight, ear, smell, memory, and attention) that in turn are programmed by genes and influenced by environmental processes (epigenetic). Today, the approach of medical research in human diseases is to isolate one disease for study; however, the presence of an additional disease (co-morbidity) or more than one disease (multimorbidity) adds complexity to the study of these conditions. This review will present the challenge of integrating psychiatric disorders at different levels of information (Gestaltomics). The implications of increasing the level of complexity, for example, studying the co-morbidity with another disease such as cancer, will also be discussed.

Muchos de los grandes problemas en salud de hoy en día pudieran ser prevenibles, incluyendo la obesidad, la diabetes, las enfermedades asociadas al consumo del tabaco y el alcohol, como son la enfermedades cardiovasculares o el cáncer. Sin embargo, la modificación de la conducta en “pro” de nuestra salud, no es un problema menor. En 2015, las Naciones Unidas se promulgaron a favor de brindar su apoyo a la salud mental para entrar como parte de las metas del desarrollo sustentable dentro de las enfermedades no transmisibles.

OBJETIVO: Estimar el riesgo para desarrollar psicopatología entre padres e hijos a lo largo de tres generaciones. MATERIAL Y MÉTODOS: Se utilizó el método del "estudio de la historia familiar". Para el estudio se utilizaron datos de una encuesta probabilística de hogares efectuada en 1995 en la Ciudad de México. Los probandos fueron adultos entre los 18 a 65 años de edad (n=1 932) a quienes se entrevistó utilizando la Entrevista Internacional Diagnóstica Compuesta. Además, se obtuvo información acerca de antecedentes psiquiátricos en sus padres empleando el método y los criterios diagnósticos de la historia familiar. Finalmente, en aquellos adultos con hijos de entre 4 a 16 años viviendo en el mismo hogar (n=925) se les aplicó un cuestionario para detectar la presencia de psicopatología en cada uno de sus hijos, obteniéndose información acerca de 1 686 niños y adolescentes. Para estimar el riesgo de morbilidad entre generaciones y la interacción entre éstas, se distinguió cuando sólo hubiera antecedentes en los abuelos, solamente en los padres y cuando estaban presentes en los abuelos y en los padres. La probabilidad de ser "caso" se obtuvo a partir de la razón de momios resultante de los análisis de regresión logística siguiendo tres diferentes modelos: el clásico, el con efectos aleatorios y el con ecuaciones de estimación generalizada con varianza robusta. RESULTADOS: La probabilidad de presentar psicopatología es entre dos a tres veces mayor cuando hay trastornos psiquiátricos en los padres. La probabilidad es mayor cuando existe comorbilidad entre diferentes tipos de trastornos. CONCLUSIONES: El riesgo para desarrollar psicopatología entre las generaciones es al menos moderado y relativamente estable. Los resultados sugieren que, en general, la transmisión de psicopatología entre las generaciones es acorde con la de un modelo genético mixto.OBJECTIVE: To estimate the risk of psychiatric disorders across three family generations. MATERIAL AND METHODS: The research design corresponds to a "family history study" and is based upon a household survey conducted in 1995, on a representative sample of Mexico City's adult population aged 18 - 65 years (n=1 932). Briefly, a standardized assessment of adults' lifetime prevalence of psychiatric disorders was obtained using an amended version of the Composite International Diagnostic Interview, CIDI. In addition, all respondents provided information on their parents' psychiatric history of anxiety, affective disorders, and substance-use disorders. Also, respondents who had 4-16 year old children living in the same household were interviewed using a standardized questionnaire that included specific questions on their children's psychiatric symptoms (n=925 parents, corresponding to 1 686 children and adolescents). Familial psychopathology across generations was defined as follows: a) history of psychiatric disorders only in grandparents; b) history of psychiatric disorders in one parent only (mother or father); and, c) history of psychiatric disorders history in grandparents and in parent. The risk of psychiatric morbidity was estimated via odds ratios obtained from logistic regression models with and without random-effects and using Generalized Estimation Equations with robust variance estimation. RESULTS: The risk for psychopathology in the offspring across generations was estimated to be two to three times higher when psychiatric disorders occurred among the parents. The risk of psychiatric disorders was estimated to be higher when comorbidity among different types of disorders was present. CONCLUSIONS: The results suggest that the risk for developing psychopathology across generations is at least moderate and relatively stable. Familial transmission of psychopathology across three generations seems to resemble a genetic mixed model.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region.