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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.

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.

Background:The last twenty years have seen major advancements in unraveling the etiology and the identification of biological markers of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococci (PANDAS). However, this body of evidence has not yet been translated into a clinical setting.Objective:We will review the most important studies to date on PANDAS, emphasizing those whose advances could improve the diagnosis of these disorders. We also suggest the need for updated diagnosis criteria integrating the recent findings from the hereby included studies.Methods:Consulting the PubMed database, a literature review of the last twenty-one years (between 1998 and 2019) was carried out using the terms “PANDAS” and “pediatric autoimmune neuropsychiatric disorders” in combination with “diagnosis” and “markers”. The search resulted in 175 hits from which we selected clinical cases, original investigations, and clinical reviews.Results:This review offers a compilation of the most important studies performed to date regarding the clinical presentation and potential biological markers of PANDAS. Moreover, we suggest the refinement of some aspects in the current diagnosis criteria, such as focusing on specific symptoms and the inclusion of neuroimaging and peripheral markers.Conclusion:The identification of specific biological markers in PANDAS is crucial for its diagnosis and opportune treatment. Future research will determine whether PANDAS require separated diagnostic and therapeutic measures or if it should be included in recently proposed categories such as Pediatric Acute Neuropsychiatric Syndrome (PANS) or Childhood Acute Neuropsychiatric Syndrome (CANS).

The aim of this study was to explore the knowledge, emotions and perceived stressors by healthcare workers who were in contact with infected patients during the COVID-19 outbreak. An online cross-sectional survey was applied. Data were collected from N = 263 healthcare workers in Tabasco State, Mexico. We developed and administered a questionnaire, which consisted of sociodemographic characteristics, plus four sections. The sections evaluated were (1) knowledge of COVID-19, (2) feelings/emotions during the COVID-19 outbreak, (3) factors that caused stress and (4) factors that helped to reduce stress. Surveyed individuals were divided into three groups: physicians, nurses and other healthcare workers. When we evaluated their knowledge of COVID-19 we observed that the majority of healthcare workers in the three groups reported that they knew about COVID-19. Physicians indicated that they felt insecure about practicing their profession (62.5%) due to the high risk of being in contact with SARS-CoV-2. With regards to stressor factors, the risk of transmitting COVID-19 to their families was the main factor causing moderate to high stress (95.4%). Finally, we found that “your profession puts your life at risk” was the only factor associated with feeling nervous and scared (PR: 3.15, 95% CI: 1.54–6.43). We recommended health education campaigns, introductory courses on COVID-19 and other infectious diseases, management protocols and the provision of protection equipment to health workers in order to reduce personal and professional fears of contagion and to improve the health system in Mexico when facing epidemics.

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.

Background Circulating cell-free mitochondrial DNA (cf-mtDNA) fragments in blood plasma have been reported in patients with schizophrenia (SZ). Although the relationship of cf-mtDNA to the cognitive status of patients with SZ has not yet been explored, it is known that cognitive impairment in SZ compromises the functional and social capacity of these patients and diminishes their quality of life. In this sense, the assessment of the severity of cognitive impairment in a Mexican population with SZ and its association with cf-mtDNA levels in blood plasma may provide the possibility of using cf-mtDNA as a biomarker to determine the status of the disease and the possible ensuing changes over time. Methods Subjects for a case-control study will be recruited. cf-mtDNA obtained from blood plasma will be quantified by real-time polymerase chain reaction, using melting curve technology with SYBR green as amplification marker. Patients with SZ will be grouped into those with severe, mild, and no cognitive impairment according to Montreal Cognitive Assessment scale scores, to determine differences between cognitive performance and cf-mtDNA levels in blood plasma. Ethics and communication This study has been approved by the ethics and investigation committees of the High Specialty Regional Hospital of Mental Health (Hospital Regional de Alta Especialidad de Salud Mental); project No. HRAESM/DG/RP/1128/2018. We plan to communicate our research findings in scientific conferences and in peer-reviewed journals. Conclusion It is known that cognitive dysfunction provokes negative effects in an SZ patient´s life. This project aims to provide better knowledge about the role of cf-mtDNA in the pathogenesis of cognitive impairment in SZ, as an attempt to achieve improvements to the existing treatments, thereby helping to prevent major cognitive deterioration.

Psychiatric disorders are complex polygenic diseases that show common genetic vulnerability. Several studies have investigated the association of polymorphisms of FK506 binding protein 51 (FKBP5) gene and depressive disorders or suicidal behavior, however, the results have been controversial and ambiguous. The aim of our study was to explore the role of the FKBP5 gene variants (rs1360780, rs3800373 and rs4713916), in depressive disorders or suicidal behavior through a systematic review and a meta-analysis. The protocol number of the study is PROSPERO CRD42018089295. The meta-analysis included 12 studies. Odds ratios with 95% confidence intervals were used to evaluate the association and the publication bias was tested by Egger's test and funnel plot; heterogeneity was assessed by the Cochran's chi-square-based Q statistic test and the inconsistency index. Our results showed that the rs3800373 and rs4713916 were associated with an increased risk of depressive disorders when using the heterozygous and dominant models. In the stratified analysis by ethnicity, a significantly increased risk of depressive disorders was also observed for rs3800373 and rs4713916 in Caucasians. When we analyzed suicidal behavior, we found a significant association with the rs1360780 of FKBP5 and suicidal behavior risk in the overall population and rs3800373 in completed suicide subgroup. Existing evidence indicates that the polymorphisms of FKBP5 gene are associated with risk of depressive disorders and suicidal behavior. Future studies with larger sample sizes will be necessary to confirm the present results.

ObjectiveAn obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype.MethodsFourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA.ResultsThe pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls.ConclusionThe results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.

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 Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

The prevalence of comorbid psychiatric disorders among patients with eating disorders (ED) is higher than the general population. Individuals diagnosed with eating disorders have changes in their body mass index which could promote severe metabolic disruptions. This study aimed (1) to report the prevalence of comorbid psychiatric disorders among a Mexican adolescent sample diagnosed with eating disorders, (2) to compare our results with the prevalence of psychiatric disorders reported from a national survey of mental health of adolescents, (3) to compare the presence of psychiatric comorbidities between ED diagnoses, and (4) to explore the relationship of these comorbidities with the body mass index. In the study, we included 187 Mexican adolescents diagnosed with eating disorders. The psychiatric comorbidities were evaluated using the Mini International Neuropsychiatric Interview for children/adolescents, and a revised questionnaire on eating and weight patterns. We found that 89% of the Mexican adolescents diagnosed with ED had another psychiatric comorbidity. Major depressive disorder (52.40%) and suicide risk (40%) were the most prevalent comorbidities. Attention and deficit hyperactivity disorder (ADHD) prevalence was different between ED diagnosis, and adolescents with binge-eating disorder and ADHD had the higher body mass index. Our results showed that in this sample of Mexican adolescents, the presence of comorbidities could impact body mass index. This emphasizes the importance that clinicians take into consideration the presence of psychiatric comorbidities to achieve an integrative treatment for adolescents diagnosed with ED.

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.

Five polymorphisms (rs4713916, rs4713902, rs1360780, rs9296158 and rs3800373) of FKBP5 gene were analyzed in a case–control study comprising 423 Mexican individuals (146 individuals with suicide attempt and 277 controls). The SNP’s were genotyped using the TaqMan-allelic assay. Genotype and allele frequencies were compared between the two groups, then the association between FKBP5 gene polymorphisms and suicide attempt was analyzed. We found a significant association of rs1360780 T minor allele (All, OR = 1.80, 95 % CI = 1.35–2.41, P = 0.0005; Males, OR = 2.25, 95 % CI = 1.44–3.50, P = 0.0002) as a suicide behavior risk factor. Conversely, rs3800373 C minor allele (All, OR = 0.61, 95 % CI = 0.46–0.83; P = 0.0013; Females, OR = 0.33, 95 % CI = 0.22–0.50; P = 0.0001) and the A-C-T-A-C haplotype (OR = 0.06, 95 % CI = 0.01−0.36; P = 0.002) were significantly associated as protective factors. No association was observed with the other SNP’s. Our study suggests that SNP’s in FKBP5 gene contribute to suicide behavior pathogenesis.

In terms of the physiological characteristics of suicidal behavior (SB) disorder, an increase inflammation response has been reported in these individuals. Therefore, the pro-inflammatory and anti-inflammatory activities of interleukins are adequate markers to research in order to understand the pathogenesis of SB. For that reason, the aim of this systematic review was to evaluate the role of interleukins in individuals with suicidal behavior disorder. A systematic search was performed in PubMed, Scopus and EBSCO databases up to July 2019. We used the words “interleukin” AND “suicide”, “interleukin” AND “suicidal”, and “IL-”. Articles where interleukins concentrations were measured in individuals with SB and/or genetic studies addressing interleukins genes variants as possible markers to SB were included. A total of 54 articles were included. Articles that measured interleukin levels comprised 1111 cases and 1588 controls; whereas the genetic studies comprised 3082 cases and 5148 controls. These studies evaluated the concentrations of IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, sIL-2R in serum, plasma. The pro-inflammatory interleukins concentrations were higher in cases than in controls; however, we observed heterogeneity in the measurements and sample sources. Whereas, 9 polymorphisms of IL-1α, IL-1β, IL-6, IL-1β-8 genes were analyzed in association with suicide behavior disorder, though no conclusive outcomes were attained. Our results suggest that individuals with suicide risk undergo continuous stress that could trigger the release and circulation of pro-inflammatory interleukins and therefore their concentration in plasma. However, more studies are necessary in order to reach conclusively outcomes.

Objective: We conducted a meta-analysis of case-control studies to determine whether leptin levels in serum contribute to the pathogenesis of suicide behavior.Methods: PubMed, EBSCO and Science Dir...

Eating disorders (ED) are characterized by disruption of eating behaviour and alteration of food intake. Leptin, is one of the main hormones that modulate food intake and are altered in individuals diagnosed with ED. Genetic risk variants for obesity, like those reported inFTO and ABCA1, have also been associated to ED disorders. The present study aimed to analysed leptin circulating levels and the interaction between obesity-risk variants in FTO and ABCA1, in adolescents diagnosed with ED. A total of 99 individuals diagnosed with ED were genotype using Taqman probes for FTO (rs9939609) and ABCA1 (p.Arg230Cys, rs9282541). Commercial enzyme-linked immunosorbent assays were utilized to determined circulating leptin. Differences in leptin concentration were analysed by t-Student or ANOVA test. Gene-gene interaction were analysed using general estimation equations. Circulating leptin levels differed between the three diagnostic groups, lead by individuals diagnosed with binge eating-disorder. In individuals with more than 3 of episodes of binge-eating per week having the highest leptin levels. Also, we found that carriers of both risk alleles had the highest leptin levels. Our observations found an interaction between FTO rs9969609 and the native American-origin ABCA1 p.Arg230Cys to modulate circulating leptin levels in Mexican adolescents diagnosed with eating-disorders.

Background It is accepted that there is a genetic factor that influences the risk of suicidal behavior. The catechol-O-methyltransferase (COMT) gene, especially the Val108/158Met polymorphism, has been associated with suicide; however, no conclusive outcome has been attained. Therefore, the aim of the present study was to assess the role of COMT Val108/158Met in suicidal behavior throughout an updated meta-analysis. Methods We performed an online search using PubMed and Web of Science (up to March 2017). Our systematic review included case-control studies of individuals who attempted suicide and completed suicide. We tested allelic, homozygous, heterozygous, dominant, and recessive inheritance models. The meta-analysis was performed in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results The meta-analysis comprised 17 studies, which included 3,282 cases and 3,774 controls, and showed that when evaluating the overall population, the Val108/158Met polymorphism of COMT was not associated with suicidal behavior in any of the inheritance models; however, the subanalyses showed that this polymorphism exhibits a risk factor in males and a protective effect in females. Additionally, it conveyed a risk factor in Asian populations when using the allelic (OR 1.25; CI: 1.04-1.51) and recessive models (OR 1.32; CI: 1.03-1.68). Conclusion Our updated meta-analysis suggests a possible association between COMT Val108/158Met and suicidal behavior in Asian populations. However, in view of the small number of studies, these results should be considered exploratory. We recommend that more studies be performed with larger samples.

In this study, we evaluated the expression profile changes of genes that intervene in the calcium signaling pathway, in young and adult Wistar rats, using the animal model of neonatal lesion in ventral hippocampus (NLVH) (a recognized animal model for schizophrenia) and compared to the group of control animals (Sham). Through microarray technology, gene expression profiles were obtained from the three brain areas (nucleus accumbens, prefrontal cortex, and hippocampus) of young male Wistar rats (45 days) and adults (90 days) whether or not subjected to NLVH. The calcium signaling pathway reported a greater number of differentially expressed genes with z-score two values, > 2 (over-expression) and

Several studies have proposed that cocoa products enriched in flavonoids reduce anxiety and depressive symptoms. (-)–Epicatechin (Epi), a flavonoid present in high concentrations in cocoa, is associated with many effects of dark chocolate and has been postulated to function as an exercise mimetic. Physical exercise is used as an adjuvant treatment for many patients with depression. This study aimed to evaluate the effect of Epi on resilience to depression-like behaviour in a murine model. Male mice were randomly selected and divided into four groups (n = 8/group). At the age of 8–9 weeks, the mice were subjected to chronic mild stress (CMS), and the two groups were treated with Epi for five weeks. Epi was administered by oral gavage twice daily for 5 weeks. The control group was housed under conditions without stress and Epi treatment. Depressive-like behaviour was evaluated by performing sucrose preference and open field tests. Interestingly, Epi reduced anhedonia and anxiogenic behaviour in the murine stress model. Our results provide evidence that Epi induces resilience to stress-induced depression through a modulatory effect on aminotransferase KAT.

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 &lt, 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.

espanolAntecedentes: la concurrencia de trastornos por uso de sustancias (TUS) es alta en personas con enfermedades psiquiatricas; Mas importante aun, las personas con ambos trastornos (diagnostico dual) tienen sintomas mas graves. Se han propuesto trastornos psiquiatricos para compartir una susceptibilidad genetica con los TUS. Para explorar esta susceptibilidad genetica compartida, analizamos si alguna de las puntuaciones de riesgo poligenico (PRS) para los trastornos psiquiatricos podria estar asociada al diagnostico dual en pacientes con esquizofrenia (SCZ) o trastorno bipolar (BD). Metodos: Se incluyeron 192 individuos de ascendencia mexicana: 72 con SCZ, 53 con BD y 67 controles no relacionados sin trastornos psiquiatricos. Derivamos calculos de PRS para trastornos del espectro autista, trastorno de deficit de atencion / hiperactivo, BD, depresion mayor y SCZ utilizando estadisticas resumidas de asociacion de genoma previamente publicadas. Resultados: Encontramos que el diagnostico dual tenia una susceptibilidad genetica compartida con el trastorno depresivo mayor (MDD) y SCZ; Ademas, en individuos con BD, PRS podria predecir el diagnostico dual para MDD. Conclusiones: Nuestros resultados refuerzan la nocion de que las personas con diagnostico dual tienen una mayor susceptibilidad genetica a desarrollar ambos trastornos. Sin embargo, se requieren analisis de muestras de mayor tamano para aclarar aun mas como predecir riesgos a traves de PRS dentro de diferentes poblaciones. EnglishBackground: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations. (REV INVEST CLIN. 2019;71:321-9)

espanolAntecedentes: la esquizofrenia (SCZ) y la demencia, a menudo relacionadas, son dos de las enfermedades neuropsiquiatricas mas comunes; Los estudios epidemiologicos han demostrado que los pacientes con SCZ presentan un riesgo 2 veces mayor de demencia en comparacion con los individuos no esquizofrenicos. Exploramos la presencia de variantes geneticas daninas raras y novedosas en pacientes diagnosticados con demencia de inicio tardio de tipo Alzheimer (DAT) o SCZ. Metodos: Incluimos 7 pacientes con DAT y 12 con SCZ y realizamos una secuenciacion dirigida de gran profundidad de 184 genes. Resultados: Encontramos variantes daninas novedosas y raras en 18 genes en estos pacientes mexicanos. Los portadores de estas variantes mostraron fenotipos extremos, incluyendo SCZ resistente al tratamiento o deterioro cognitivo. Ademas, encontramos una variacion en ABCC1 como un posible vinculo entre la psicosis y el deterioro cognitivo. Discusion: Como analisis exploratorio, informamos algunas variaciones interesantes que deberian corroborarse en estudios de mayor tamano de muestra. EnglishBackground: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer’s type (DAT) or SCZ. Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies. (REV INVEST CLIN. 2019;71:246-54)

Background Suicide rates vary substantially by sex. Suicides committed by males significantly outnumber female suicides. Disparities in community and social factors provide a partial explanation for this phenomenon. Thus, the evaluation of sex differences at a biological level might contribute to the elucidation of the factors involved in this imbalance. The aim of the present study was to evaluate sex-specific gene expression patterns in the suicidal brain. Methods postmortem samples from the dorsolateral prefrontal cortex (DLPFC) of 75 Latino individuals were analyzed. We considered the following groups: i) male suicides (n = 38), ii) female suicides (n = 10), iii) male controls (n = 20), and iv) female controls (n = 7). Gene expression profiles were evaluated by microarrays. Differentially expressed genes among the groups were identified with a linear model. Similarities and differences in the gene sets between the sexes were identified. Results Differentially expressed genes were identified between suicides and controls of each sex: 1,729 genes in females and 1,997 genes in males. Female-exclusive suicide genes were related to cell proliferation and immune response. Meanwhile, male-exclusive suicide genes were associated to DNA binding and ribonucleic protein complex. Sex-independent suicide genes showed enrichment in mitochondrial and vesicular functions. Limitations Relatively small sample size. Our diagnosis approach was limited to information found on coroner's records. The analysis was limited to a single brain area (DLPFC) and we used microarrays. Conclusion Previously unexplored sex differences in the brain gene expression of suicide completers were identified, providing valuable foundation for the evaluation of sex-specific factors in suicide.

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.

IntroductionSuicidality is a complex behaviour and a major health problem; the specific features that could predispose to suicidal behaviour have been extensively investigated, most frequently in European and Asian populations. Therefore, our aim is to present a protocol that will explore suicide attempt in Mexican individuals diagnosed with psychiatric disorders, through a genome-wide association study (GWAS).Method and analysisWe will perform a GWAS by comparing 700 individuals who have suicide attempt history, with control subjects without suicide attempt history (n=500). The genotyping will be conducted using the Infinium PsychArray BeadChip and quality controls will be applied to single nucleotides (SNPs) genotyped. After that, we will perform the imputation using reference panels provided by the Haplotype Reference Consortium. We will perform two different workflows: (A) the classic GWAS analysis applying the same weight to all the variants and (B) an algorithm with prediction of deleteriousness of variants.Ethics and disseminationThis study was approved by the ethics and investigation committees of the National Institute of Genomic Medicine on 22 July 2015, No CEI 215/13. We plan to disseminate research findings in scientific conferences and as a manuscript in peer-reviewed journals.Trial registration numberCEI 215/13.

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.

espanolIntroduccion: En Mexico, la prevalencia de los trastornos neurocognitivos (TNC) han aumentado a la par del incremento en la esperanza de vida. El alelo E4 del gen que codifica la apolipoproteina E (APOE) es el principal factor de riesgo genetico para deterioro neurocognitivo. Objetivo: Reproducir la asociacion en poblacion mexicana entre APOE-E4 y el deterioro neurocognitivo, asi como implementar un programa de deteccion de riesgo genetico con el alelo APOE-E4. Metodo: Se estructuro un programa de deteccion de riesgo basado en APO-EA en diferentes centros de reclutamiento en la zona centro de la Republica Mexicana, con tres etapas: reclutamiento y seleccion de los candidatos para la deteccion del alelo de riesgo, analisis del riesgo genetico y entrega del resultado. Resultados: El analisis de asociacion genetica para replicar la asociacion con trastornos neurocognitivos mediante modelos logisticos multivariados mostro que el alelo E4 de APOE incremento aproximadamente 6 % el riesgo en poblacion mexicana (RM = 5.83, p = 0.0025). Se entregaron 367 resultados de riesgo genetico. Conclusiones: El presente programa es el primero en Mexico implementado para dar a conocer un factor de riesgo genetico para trastornos neurocognitivos en varios centros del pais. EnglishIntroduction: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. Objective: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. Method: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. Results: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. Conclusions: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.

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.

Cortisol can be considered as one biomarker for diagnosis of suicide; nevertheless, several studies have shown conflicting results. This study aimed to evaluate the levels of cortisol in individuals with suicide behavior and controls (healthy or with other psychiatric disorders). Published articles were searched on online databases (PubMed, Scopus and EBSCO). Standardized mean differences (SMD), heterogeneity, publication bias and sensitivity were assessed using the Comprehensive Meta-Analysis (CMA) statistical software. The meta-analysis comprised 30 studies that provided 1775 cases, and 2162 controls (696 healthy individuals and 1465 individuals with other psychiatric diagnoses). The pooled results revealed that cortisol levels were higher in individuals with suicide behavior (SMD = 0.92, 95%CI = 0.26; 1.57, P = 0.006; I2 = 88%, Q

Mirna Edith Morales-Marín,1 Alma Delia Genis-Mendoza,1,2 Carlos Alfonso Tovilla-Zarate,3 Nuria Lanzagorta,4 Michael Escamilla,5 Humberto Nicolini1,4 1Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), CDMX, Mexico; 2Psychiatric Care Services, Child Psychiatric Hospital Dr Juan N Navarro, CDMX, Mexico; 3Genomics Research Center, Juarez Autonomous University of Tabasco, Comalcalco, Mexico; 4Carracci Medical Group, CDMX, Mexico; 5Department of Psychiatry, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso TX, USA Background: The brain-derived neurotrophic factor (BDNF) has been considered as an important candidate gene in bipolar disorder (BD); this association has been derived from several genetic and genome-wide studies. A polymorphic variant of the BDNF (Val66Met) confers some differences in the clinical presentation of affective disorders. In this study, we evaluated a sample population from Mexico City to determine whether the BDNF (rs6265) Val66Met polymorphism is associated with the body mass index (BMI) of patients with BD.Methods: This association study included a sample population of 357 individuals recruited in Mexico City. A total of 139 participants were diagnosed with BD and 137 were classified as psychiatrically healthy controls (all individuals were interviewed and evaluated by the Diagnostic Interview for Genetic Studies). Genomic DNA was extracted from peripheral blood leukocytes. The quantitative polymerase chain reaction (qPCR) assay was performed in 96-well plates using the TaqMan Universal Thermal Cycling Protocol. After the PCR end point was reached, fluorescence intensity was measured in a 7,500 real-time PCR system and evaluated using the SDS v2.1 software, results were analyzed with Finetti and SPSS software. Concerning BMI stratification, random groups were defined as follows: normal 30 kg/m2.Results: In the present work, we report the association of a particular BMI phenotype with the presence of the Val66Met allele in patients with BD (P=0.0033 and odds ratio [95% confidence interval] =0.332 [157–0.703]), and correlated the risk for valine allele carriers with Ow and Ob in patients with BD.Conclusion: We found that the methionine allele confers a lower risk of developing Ow and Ob in patients with BD. We also confirmed that the G polymorphism represents a risk of developing Ow and Ob in patients with BD. In future studies, the haplotype analysis should provide additional evidence that BDNF may be associated with BD and BMI within the Mexican population. Keywords: brain-derived neurotrophic factor, bipolar disorder, single nucleotide polymorphism, body mass index

Schizophrenia (SCZ) and bipolar disorder (BD) cause similar symptomatology. A correlation between these disorders has been found. We aimed to explore shared CNVs between SCZ and BD, in 35 sibpairs diagnosed with SCZ and 21 sibpairs diagnosed with BD. CNV calling was performed using data derived of Psycharray, by PennCNV. We did not find any shared CNVs between individuals diagnosed with BD and SCZ, neither with psychotic symptoms in individuals with BD. Nevertheless, we found a significant higher CNV burden in early-onset SCZ. This is one of the first's studies analyzing shared CNVs between SCZ and BD in Mexican population.

Orexins (OXs) system has been suggested to play a key role in regulate processes related to arousal, including anxious behaviors. However, until now, the contribution of OXs in anxiogenic-like effects has not been completely clear, particularly in rats, whose results are not yet conclusive in behavioral-tests such as elevated-plus-maze test (EPM-test). The goal of this study was to explore the anxiogenic-like effect induced by orexin-A (OX-A) using two different paradigms; the EPM-test and simultaneously a quantitative index in vivo , the cortical-electroencephalographic-(EEG)-record. This index proposes that a low-frequency domain EEG, particularly 0.5–5-Hz (delta and low portion of theta-waves), is a key indicator to evaluate anxiety levels. We also explored whether the anxious effect of OX-A could be altered by an antagonist of dopamine-D2-receptor (D 2 R) sulpiride (SUL). Our results showed that intracerebroventricular (i.c.v.) injection of a low dose of OX-A (140 pmol) did not increase anxiety levels in rats. On the other hand, cortical-EEG-activity showed only a decrease in delta-spectral-power but no changes in theta-potency. These data suggest that the reduction in delta-power induced by OX-A only keeps the animals awake and alert without changes in anxiety levels.

Background: The aim of this study was to analyze the possible association of polymorphic variants of the DRD2 and ANKK1 genes with suicide attempt in a Mexican population. Methods: We conducted a case-control study in 289 subjects (166 suicide attempters and 123 healthy controls). We genotyped 2 polymorphisms of DRD2 (rs6275 and rs1799978) and 1 polymorphism of ANKK1 (rs1800497); then we analyzed the association between suicide attempt and these polymorphisms through genotypes, alleles, and inheritance models. Results: Individuals who carried the TT genotype of the rs1800497 showed a 3-fold risk of attempting suicide (OR = 3.01; 95% CI 1.56–5.81, p = 0.001) when evaluated through the recessive model. In an analysis stratified by gender, this risk factor remained present among females (OR = 2.81; 95% CI 1.37–5.75) as well as males (OR = 3.3; 95% CI 1.01–10.77). Conclusion: Our results suggest that the rs1800497 variant of the ANKK1 gene could increase the risk of suicide attempt in a Mexican population. However, further studies using larger samples are necessary to obtain more conclusive results.

Artificial sweeteners are mainly used as substitutes for sucrose derivates. In this study, we analyzed if the chronic consumption of aspartame or acesulfame potassium at an early age, produces histological alterations, astrogliosis and decreased neuronal viability, in hippocampus, prefrontal cortex, amygdala and hypothalamus of male Wistar rats. A histological analysis was performed on male Wistar rats that consumed aspartame or acesulfame potassium during 90 days, initiating the consumption of sweeteners immediately after weaning. The evaluation of neuronal morphology in different areas of the brain was performed with hematoxylin - eosin staining. To measure astrogliosis and neuronal viability, we used the immunohistochemical technique, with the glial fibrillary acidic protein immunomodulators (GFAP) and with neuronal-specific enolase (NSE). The consumption of aspartame or acesulfame potassium promoted morphological changes of neurons including increased pyknotic nuclei and vacuolization in all the brain areas studied. In hippocampus, prefrontal cortex, amygdala and hypothalamus, astrogliosis and reduction of neural viability were observed in sweeteners consumers in comparison with the control group. Chronic consumption of ASP and ACK from early stages of development and during long periods, may promote neural modifications, astrogliosis and decrease neuronal viability in prefrontal cortex, amygdala, hippocampus, and hypothalamus.

Background The association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia. Methods The search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case–control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Results The meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30–1.14) and C957T (additive model: OR 0.75, 95% OR 0.58–0.97, recessive model: OR 0.79, 95% CI 0.64–0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04–1.70). Conclusion Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population. Electronic supplementary material The online version of this article (doi:10.1186/s12993-016-0114-z) contains supplementary material, which is available to authorized users.

Background Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. Methods The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5–7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. Results In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p