CRISPR/Cas9 genome editing approaches for psychiatric research

Currently, genome editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), are predominantly used to model genetic diseases. This genome editing system can correct point or frameshift mutations in risk genes. Here, we analyze and discuss the advantages of genome editing, its current applications, and the feasibility of the CRISPR/Cas9 system in research on psychiatric disorders. These disorders produce cognitive and behavioral alterations and their etiology is associated with polygenetic and environmental factors. CRISPR/Cas9 may reveal the biological mechanisms of psychiatric disorders at a basic research level, translating a suitable clinical approach for use in the diagnosis and treatment of psychiatric disorders. Genetic diagnosis and treatment for these disorders have not yet been fully established in psychiatry due to the limited understanding of their heterogeneity and polygenicity. We discuss the challenges and ethical issues in using CRISPR/Cas9 as a tool for diagnosis or gene therapy.

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

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

High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case-Control Study.

Suicide attempts are an emerging health problem around the world. Increased levels of IL-6 have been associated with suicidal behavior. Therefore, the aims of this study were to evaluate the serum levels of IL-6 in individuals with suicide attempts and a comparison group and to associate the IL-6 levels with the lethality of the suicide attempt. Additionally, we associated the rs2228145 polymorphism of the IL6R gene with suicide attempts or with the IL-6 serum levels. Suicide attempts and their lethality were evaluated using the Columbia Suicide Severity Rating Scale. The serum concentrations of IL-6 were measured by the ELISA technique in individuals with suicide attempts and then compared to a control group. The rs2228145 polymorphism of the IL6R gene was analyzed by real-time polymerase chain reaction. We found elevated serum levels of IL-6 in the suicide attempt group when compared to the control group (F = 10.37, p = 0.002). However, we found no differences of the IL-6 levels between high and low lethality. The IL6R gene polymorphism rs2479409 was not associated with suicide attempts. Our data suggest that IL-6 serum is increased in individuals with suicide attempts.

Cannabis smoking increases the risk of suicide ideation and suicide attempt in young individuals of 11-21 years: A systematic review and meta-analysis.

BACKGROUND: Cannabis is the most frequently consumed drug around the world. Its use has been associated with increased suicide behaviors; nonetheless, the association of cannabis smoking and suicide behaviors in adolescents has not yet been established. The aim of this systematic review and meta-analysis was to evaluate the risk of suicide attempt, suicidal ideation or suicide planning in individuals of 11-21 years of age who smoke cannabis. METHODS: We performed an online searched using PubMed, EBSCO and Science Direct databases, up to July 2021. We calculated odds ratio with 95% confidence intervals to evaluate the association between suicide attempt, suicidal ideation or suicide planning and cannabis smoking in individuals of 11-21 years of age. RESULTS: Twenty studies reported suicide attempts in 34,859 young individuals, suicidal ideation in 26, 937 individuals, and suicide planning in 9054 young individuals. We found an increased risk of suicide attempt in cannabis smokers than in non-cannabis users (OR: 2.33; 95% CI: 1.78-3.05; Z p value; <0.0001; I2 = 97.12%), as well as a significant association between cannabis smoking and suicidal ideation (OR: 2.04; 95%CI: 1.64-2.53; Z p value: <0.001; I2: 94.88) and suicide planning (OR: 1.674; 95% CI: 1.554-1.804; Z p value: 0.000; I2: 92.609). Subgroup analyses showed that American teens have an increased risk of suicidal ideation; the meta-regression analysis revealed that age was negatively associated with the risk of suicide attempt. CONCLUSIONS: This meta-analysis shows that cannabis smoking increased the risk of suicide attempt, suicidal ideation and suicide planning in young individuals of 11-21 years of age. The high risk of suicide behaviors could vary depending on the population studied; therefore, more studies are necessary to corroborate the risk of presenting suicide behaviors in individuals of 11-21 years of age who smoke cannabis.

Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis

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.

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

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

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

Cannabis Use in People With Obsessive-Compulsive Symptomatology: Results From a Mexican Epidemiological Sample.

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.

Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.

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 < 5.00e-05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (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.

Brain Gene Expression-DNA Methylation Correlation in Suicide Completers: Preliminary Results

Abstract Background: Gene expression alterations have been implicated in suicide pathology. However, the study of the regulatory effect of DNA methylation on gene expression in the suicidal brain has been restricted to candidate genes. Objective: The objective of the study was to identify genes whose expression levels are correlated with DNA methylation in the prefrontal cortex of suicides. Methods: Postmortem prefrontal cortex samples from 21 suicides and six non-suicides were collected. Transcriptomic and DNA methylation profiles were evaluated with microarrays; cis correlations between gene expression and CpG methylation were screened. We then analyzed the presence of transcription factor (TF) binding sites (TFBS) at CpG sites correlated with gene expression. Gene expression of TFs involved in neurodevelopmental binding to predicted TFBS was determined in the BrainSpan database. Results: We identified 22 CpG sites whose methylation levels correlated with gene expression in the prefrontal cortex of suicides. Genes annotated to identified CpG sites were involved in neurodevelopment (BBS4, NKX6-2, AXL, CTNND1, and MBP) and polyamine metabolism (polyamine oxidase [PAOX]). Such correlations were not detected in the non-suicide group. Nine TFs (USF1, TBP, SF1, NRF1, RFX1, SP3, PKNOX1, MAZ, and POU3F2) showed differential expression in pre- and post-natal developmental periods, according to BrainSpan database. Conclusions: The integration of different omic technologies provided novel candidates for the investigation of genes whose expression is altered in the suicidal brain and their potential regulatory mechanisms. (REV INVEST CLIN. 2020;72(5):283-92)

Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci / Asociación de títulos de anticuerpos y polimorfismos del gen 5-HTTLPR en trastornos pediátricos neuropsiquiátricos autoinmunes asociados con estreptococo

Abstract Introduction It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5' promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL >SL >SS. Discussion and conclusion This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.

Resumen Introducción Se ha hipotetizado que el trastorno pediátrico neuropsiquiátrico autoinmune asociado a estreptococo (PANDAS) es resultado de una respuesta inmune anormal a una infección estreptocócica. Existe evidencia de que el sistema serotoninérgico está involucrado tanto en la fisiopatología del trastorno obsesivo compulsivo (TOC) como en procesos inmunológicos. En la región promotora de 5-HTT, gen que codifica el transportador de serotonina, podemos encontrar el polimorfismo 5-HTTLPR que se ha asociado con el TOC. Siendo PANDAS un trastorno con síntomas de TOC y probables anormalidades inmunes, los polimorfismos de 5-HTT pueden ser relevantes en este trastorno. Objetivo Evaluar la asociación entre los genotipos de 5-HT y la presencia de anticuerpos séricos en pacientes con PANDAS. Método Comparamos la frecuencia de genotipos de 5-HT y los títulos de anticuerpos anti-estreptococo, antineurales y antienolasa en suero de 56 pacientes con PANDAS y 20 controles sanos de México y Cuba. Resultados Los títulos de anticuerpos antienolasa y antiestreptococo fueron mayores en pacientes con PANDAS en comparación con los controles. El título de anticuerpos antienolasa y antineural aumentó de acuerdo con el polimorfismo de los pacientes con PANDAS de la siguiente manera: LL >SL >SS. Discusión y conclusión Éste es el primer estudio que evalúa la asociación entre los genotipos de 5-HTTLPR y anticuerpos en pacientes con PANDAS. Las asociaciones entre polimorfismos de genes serotoninérgicos y la respuesta inmune podrían proporcionar información sobre la interacción entre ambos sistemas. Nuestros resultados sugieren una asociación entre el alelo S y niveles altos de anticuerpos en pacientes con PANDAS.

Advanced paternal age as a risk factor for autism spectrum disorder in a Mexican population / Edad paterna avanzada como factor de riesgo para el trastorno del espectro autista en una población mexicana

Abstract Introduction Risk factors for autism spectrum disorders (ASD) have been identified, as is the case of advanced parental age. Advanced parental age as an ASD risk factor has been studied in Scandinavian populations; there are no reports for Mexican children. Objective The present work aim is to analyze if advanced parental age is a risk factor for ASD in a Mexican children sample. Method Mexican children (N = 1 068) participated in a case-control study, 162 had an ASD diagnosis. Multivariate logistic regression adjusted by cofounders was performed to explore the effect of paternal age on ASD risk. Results Advanced paternal age in Mexican children increases the risk for ASD, and also, a difference of 10 years between parental ages have a higher risk. Discussion and conclusion The effect of advanced paternal age in Mexican children was lower than those reported previously for other populations. Advanced paternal age and difference between parental ages could be a risk factor for ASD in Mexican population. Nevertheless, the analysis of larger sample sizes is required.

Resumen Introducción Se han identificado algunos factores de riesgo para el trastorno del espectro autista (TEA) como es el caso de la edad parental avanzada. La edad parental avanzada es un factor de riesgo que ha sido muy explorado en poblaciones escandinavas; sin embargo, no existen reportes en niños de ascendencia mexicana. Objetivo El presente trabajo tiene el objetivo de analizar si la edad parental avanzada es un factor de riesgo para TEA en una muestra de niños mexicanos. Método Un total de 1 068 niños de la Ciudad de México se incluyeron en un estudio de casos-controles, de los cuáles 162 contaban con diagnóstico de TEA. Regresiones logísticas multivariable, ajustadas por confusores, se realizaron para explorar el efecto de la edad parental avanzada en el riesgo para TEA. Resultados La edad paterna avanzada en niños mexicanos aumentó el riesgo para TEA; también, una diferencia de edad de 10 años entre los padres presenta un mayor riesgo. Discusión y conclusión El efecto de la edad paterna avanzada en los niños mexicanos fue mucho más bajo que aquella reportada para otras poblaciones. La edad paterna avanzada y la diferencia entre la edad parental puede ser un factor de riesgo para TEA en población mexicana. Sin embargo, se requieren análisis en poblaciones con mayor tamaño de muestra.

The Identification of Admixture Patterns Could Refine Pharmacogenetic Counseling: Analysis of a Population-Based Sample in Mexico.

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.

Exploratory analysis of polygenic risk scores for psychiatric disorders: Applied to dual diagnosis

Background 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.

Exploratory analysis of rare and novel variants in Mexican patients diagnosed with schizophrenia and dementia

Abstract Background 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.

Effect of the polymorphism BDNF rs6265 G/A in Mexican outpatient children with autism spectrum disorders / Efecto del polimorfismo rs6265 G/A del gen BDNF en niños mexicanos ambulatorios con trastornos del espectro autista

Abstract: Introduction: The study of autistic spectrum disorders (ASD) at the genetic level is extremely important to understand their origin. In Mexico, there are few works addressed from this perspective. Objective: We investigated the role of the Brain Derived Neurotrophic Factor (BDNF) gene variant rs6265 G/A for single nucleotide polymorphism analysis in Mexican children with ASD using a case-control association design. Method: We made a pilot study by case-control analysis adjusting by gender, age, and ancestry. Results: Our study found no association between the BDNF rs6265 gene polymorphism and ASD [p = .419, OR = 1.597 (.514, 4.967)] Discussion and conclusion: Worldwide, the results of case-control association studies with the rs6265 of BDNF are controversial and do not always replicate. This may be due to the ethnicity of our population and additional factors not studied in the present work. Our study suggests that the SNP rs6265 is not contributing for ASD susceptibility in Mexican population.

Resumen: Introducción: El estudio de los trastornos del espectro autista a nivel genético es de suma importancia para entender su origen. En México existen pocos trabajos abordados desde esta perspectiva. Objetivo: Investigamos el papel de la variante del gen rs6265 G/A del factor neurotrófico derivado del cerebro (BDNF) para el análisis del polimorfismo de un solo nucleótido en niños mexicanos con TEA por medio de un diseño de asociación de casos y controles. Método: Realizamos un estudio piloto mediante un análisis de casos y controles ajustando por género, edad y ancestría. Resultados: Nuestro estudio no encontró asociación entre el polimorfismo del gen BDNF rs6265 y TEA [p = .419, OR = 1.597 (.514, 4.967)]. Discusión y conclusión: A nivel mundial, los resultados de estudios de asociación caso-control con el rs6265 de BDNF son controvertidos y no siempre se replican. Esto puede deberse a la etnicidad de nuestra población y a otros factores no estudiados en el presente trabajo. El estudio sugiere que el SNP rs6265 no contribuye a la susceptibilidad al TEA en población mexicana.

"Gestaltomics": Systems Biology Schemes for the Study of Neuropsychiatric Diseases.

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.

Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.

OBJECTIVES: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. METHODS: A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. RESULTS: Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. CONCLUSIONS: These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.

Cigarette smoking in patients with obsessive compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS).

Obsessive compulsive disorder (OCD) showed a lower prevalence of cigarette smoking compared to other psychiatric disorders in previous and recent reports. We assessed the prevalence and clinical correlates of the phenomenon in an international sample of 504 OCD patients recruited through the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) network. Cigarette smoking showed a cross-sectional prevalence of 24.4% in the sample, with significant differences across countries. Females were more represented among smoking patients (16% vs 7%; p<.001). Patients with comorbid Tourette's syndrome (p<.05) and tic disorder (p<.05) were also more represented among smoking subjects. Former smokers reported a higher number of suicide attempts (p<.05). We found a lower cross-sectional prevalence of smoking among OCD patients compared to findings from previous studies in patients with other psychiatric disorders but higher compared to previous and more recent OCD studies. Geographic differences were found and smoking was more common in females and comorbid Tourette's syndrome/tic disorder.