Search

Coronaviruses are neurotropic viruses capable of entering the brain through various mechanisms and generating an important inflammatory response that is capable of triggering neuropsychiatric manifestations. Several reports describe the appearance of different conditions, such as sleep problems, anxiety and depression disorders, acute psychotic disorders, encephalitis, and delirium, among others, associated with COVID-19 infection. We performed a literature review in PubMed, Springer, Nature, MDPI, and other scientific journals on the relationship between COVID-19 infection with the development and aggravation of neuropsychiatric manifestations explained by molecular changes secondary to SARS-CoV-2 where it was found that there is a relationship between the virus and the development of these manifestations. Prospective neuropsychiatric follow-up of people exposed to SARS-CoV-2 at different points in their lives, as well as their neuroimmunological status, is necessary to fully understand the long-term impact of COVID-19 on mental health. It is required to identify the risk of developing neuropsychiatric problems due to COVID-19 infection to provide better medical care from a multidisciplinary team and improve the prognosis of these patients as well as the treatment of long-term sequelae.

Research reported that sucralose induces metabolic derangements via gut microbiota modulation. However, rebaudioside A (reb A) exposure on gut microbiota has barely been evaluated. The aim of this study was to examine the gut microbiota response to sucralose or reb A in rats under two dietary conditions. Male Wistar rats (150–200 g) on normal diet (ND) or high-fat diet (HFD) were randomized to receive sucralose (SCL), reb A (REB), glucose (GLU, control), or sucrose (SUC). After eight weeks, fecal samples were analyzed by 16S ribosomal RNA gene sequencing. The diversity and the structure of the gut microbiota were not modified by NNS. In ND rats, SCL decreased phylum Firmicutes and increased Bacteroidetes and its genus Bacteroidia. At class level, in HFD rats, REB reduced Bacilli proportions. The genus Romboutsia was reduced with SCL and REB along ND. Lactobacillus increased with SCL and reduced with REB in HFD. After comparative analyses between the two types of diets, we observed that only HFD in combination with SCL increased Bacilli and diminished Bacteroidiaabundances relative to ND. Exposure to NNS, at equivalent doses to the ADI, slightly induce modifications on gut microbiota in ND and HFD feeding rats, and the effects were more pronounced with sucralose ingestion combined with the HFD regimen. Further studies are needed to examine the potential mechanisms involved.

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.

Several studies have evaluated the possible association between polymorphisms or variants in Corticotropin-releasing hormone 1 receptor gene (CRHR1) with depression; however, results remain contradictory and heterogeneous. To our knowledge, we conducted the first comprehensive systematic review and meta-analysis evaluating the association of the CRHR1 gene and the risk of depression. A search online was conducted in databases for any CRHR1 genetic association studies in depression. Data were extracted for evaluation of pooled estimates using meta-analytic techniques. Statistical analyses were performed using the Comprehensive Meta-analysis, v2.0 software. A total of 1403 cases and 2353 mentally healthy controls were included in this study. We found a significant association of rs242941, rs1876828 and rs242939 variants of the CRHR1 gene with depression. No association of CRHR1 rs110402 and depression was observed. Our meta-analysis shows that some variants of the CRHR1 gene (rs242941, rs1876828 and rs242939) might confer susceptibility to depression. Further studies with larger sample sizes need to be conducted.

ObjectivesWe aimed to examine the association ofTPH1polymorphisms 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 betweenTPH1gene 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 forTPH1A218C 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 ofTPH1gene 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.

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

Resumen Antecedentes La aceleracion del reloj epigenetico se ha asociado con una reduccion en la esperanza de vida. Los individuos con diagnostico de algun trastorno psiquiatrico presentan una reduccion en la esperanza de vida, y algunos estudios la han correlacionado con un envejecimiento acelerado. Objetivo El presente estudio tiene el objetivo de explorar si la presencia de algun trastorno psiquiatrico podria acelerar el reloj epigenetico en gemelos monocigoticos. Metodos Se incluyeron un total de 15 pares de gemelos monocigoticos. La edad epigenetica en celulas de sangre periferica fue estimada mediante algoritmos publicados previamente, utilizando el microarreglo 450 K Beadchip. Resultados Encontramos que en los gemelos con diagnostico de algun trastorno psiquiatrico podria aumentar el reloj epigenetico en comparacion con su gemelo sin trastorno psiquiatrico. Discusion y conclusion La presencia de algun trastorno psiquiatrico podria acelerar el reloj epigenetico en gemelos homocigoticos, pero se requieren estudios con muestras de mayor tamano para aclarar esta relacion.

Schizophrenia (SZ) is a mental disorder characterized by neurocognitive dysfunctions and a reduction in occupational and social functioning. Several studies have provided evidence for mitochondrial dysfunction in the pathophysiology of SZ. In this sense, it is known that the addition of genetic variations in mitochondrial DNA (mtDNA) impairs oxidative phosphorylation of enzymatic complexes in mitochondria, resulting in ATP depletion and subsequent enhancement of reactive oxygen species; this is associated with cellular degeneration and apoptosis observed in some neuropsychiatric disorders. As a consequence of mitochondrial dysfunction, an increase in circulating cell-free mtDNA fragments can occur, which has been observed in individuals with SZ. Moreover, due to the bacterial origin of mitochondria, these cell-free mtDNA fragments in blood plasma may induce inflammatory and immunogenic responses, especially when their release is enhanced in specific disease conditions. However, the exact mechanism by which mtDNA could be released into blood plasma is not yet clear. Therefore, the aims of this review article were to discuss the participation of mtDNA genetic variations in physiopathologic mechanisms of SZ, and to determine the status of the disease and the possible ensuing changes over time by using circulating cell-free mtDNA fragments as a biomarker.

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.

In Mexico, over 10 million persons are currently smokers. The motivation to quit smoking can be associated with individual and mental health factors. The aim of this study was to determine which variables related to smoking behavior, demographics, and current psychological symptoms distinguish highly motivated smokers (action stage) from less motivated smokers (planning stage) according to the readiness-to-quit model. 108 current smokers with no psychiatric diagnoses and no previous specialized attention for smoking cessation were interviewed. Nicotine dependence, readiness to quit, and psychological symptoms were assessed. Nicotine dependence was low to moderate (94.5%). Fewer depressive symptoms and smoking fewer cigarettes per day were the most important predictors for action motivation to quit. In assessing the motivation to quit smoking, individual demographic, background, and psychological characteristics should be considered since they can hinder the smoking cessation intervention.

espanolIntroduccion. 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 ninos 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 ninos mexicanos. Metodo. Un total de 1 068 ninos de la Ciudad de Mexico se incluyeron en un estudio de casos-controles, de los cuales 162 contaban con diagnostico de TEA. Regresiones logisticas 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 ninos mexicanos aumento el riesgo para TEA; tambien, una diferencia de edad de 10 anos entre los padres presenta un mayor riesgo. Discusion y conclusion. El efecto de la edad paterna avanzada en los ninos mexicanos fue mucho mas 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 poblacion mexicana. Sin embargo, se requieren analisis en poblaciones con mayor tamano de muestra EnglishIntroduction. 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.

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.

The COVID-19 pandemic has had an impact on mental health in the general population, but no systematic synthesis of evidence of this effect has been undertaken for the Mexican population. Relevant studies were identified through the systematic search in five databases until December, 2021. The selection of studies and the evaluation of their methodological quality were performed in pairs. The Newcastle-Ottawa Scale (NOS) was used for study quality appraisal. The protocol of this systematic review was registered with PROSPERO (protocol ID: CRD42021278868). This review included 15 studies, which ranged from 252 to 9361 participants, with a total of 26,799 participants. The findings show that COVID-19 has an impact on the Mexican population’s mental health and is particularly associated with anxiety, depression, stress and distress. Females and younger age are risk factors for development mental health symptoms. Mitigating the negative effects of COVID-19 on mental health should be a public health priority in Mexico.

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.

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.

Several association studies have indicated that the HTR1A gene is associated with suicidal behavior (SB). Thus, a systematic assessment of the association of HTR1A was performed based on a literature review and pooled analysis. Four electronic databases were comprehensively searched to find and pinpoint all case-control articles related to this study. When analyzing the genetic association with SB, data were divided into: (A) SB cases vs. healthy controls and (B) SB cases vs. psychiatric controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed as measures of association. Heterogeneity among included studies was analyzed using sensitivity test and Q statistics. Publication bias was also explored by Egger and rank correlation test. Thirteen case-control studies were selected in this meta-analysis, involving 2817 SB patients, 2563 healthy controls and 545 psychiatric controls. In the overall comparison between SB cases and healthy controls, result showed that the rs6295 polymorphisms of HTR1A gene was associated with SB, but only when using the recessive model (OR = 2.21, 95% CI = 1.80-2.71, P 0.001). In the smaller sample size comparison between SB and psychiatric controls, no significant association was detected with rs6295 in any of the five genetics models tested. The present meta-analysis suggests that rs6295 polymorphism of HTR1A gene could increase the risk for SB. Well-designed studies with more patients will be required to validate these results.

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.

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

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.

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.

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.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.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; IThis 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.

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 determine the risk of having significant depressive symptoms in subjects with obesity and type 2 diabetes mellitus through a meta-analysis. Our results showed that individuals with obesity and diabetes have an increased risk of having significant symptoms of depression. In subgroup analyses, we observed that Caucasian populations have an increased risk of having these symptoms. Our meta-analysis suggests that obesity is associated with an increased risk of having significant depressive symptoms in patients with type 2 diabetes, and they could be even higher in Caucasian populations.

Genetic factors have been implicated in suicidal behavior. It has been suggested that one of the roles of genetic factors in suicide could be represented by the effect of genetic variants on gene expression regulation. Alteration in the expression of genes participating in multiple biological systems in the suicidal brain has been demonstrated, so it is imperative to identify genetic variants that could influence gene expression or its regulatory mechanisms. In this study, we integrated DNA methylation, gene expression, and genotype data from the prefrontal cortex of suicides to identify genetic variants that could be factors in the regulation of gene expression, generally called quantitative trait locus (xQTLs). We identify 6,224 methylation quantitative trait loci and 2,239 expression quantitative trait loci (eQTLs) in the prefrontal cortex of suicide completers. The xQTLs identified influence the expression of genes involved in neurodevelopment and cell organization. Two of the eQTLs identified (rs8065311 and rs1019238) were previously associated with cannabis dependence, highlighting a candidate genetic variant for the increased suicide risk in subjects with substance use disorders. Our findings suggest that genetic variants may regulate gene expression in the prefrontal cortex of suicides through the modulation of promoter and enhancer activity, and to a lesser extent, binding transcription factors.

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.

Evidence suggests that interleukin-6 (IL-6) concentrations have an important role in suicide behavior (SB) as they are usually increased in these individuals, although no conclusive outcomes have been attained. The purpose of this study was to evaluate the IL-6 levels in plasma, serum, and cerebral spinal fluid (CSF) to determine through a meta-analysis if these levels are increased in individuals with SB in comparison to a group. We calculated the standardized mean difference and 95% confidence intervals (95% CIs). In the systematic review, 21 studies were included, while in the meta-analysis, we included nine studies. The results of our meta-analysis indicated that individuals with SB had reduced levels of IL-6 in plasma (

Schizophrenia is a mental and disabling disease. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in individuals with schizophrenia have been inconsistent across studies. We performed a meta-analysis to evaluate oxytocin levels in plasma, serum and cerebrospinal fluid to see if there are statistically different concentrations between individuals with schizophrenia and the comparison group.The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to guarantee a high quality and reproducibility.Following the inclusion and exclusion criteria, 14 studies were included in the meta-analysis. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using the Comprehensive Meta-analysis software with the standardized mean difference (SMD) and 95% confidence intervals (CIs).Serum oxytocin levels in individuals with schizophrenia were significantly lower than that in comparison group (SMD = − 1.74, 95% CI = − 3.22 to − 0.26, p = 0.02) but cerebrospinal fluid oxytocin levels in individuals with schizophrenia were significantly higher than those in the comparison group (SMD = 0.55, 95% CI = 0.05 to 1.04, p = 0.03).Our results suggest that oxytocin levels in cerebrospinal fluid are increased in individuals with schizophrenia but decreased in serum. Therefore, the oxytocin system dysregulation may play a role in the pathophysiology of schizophrenia and it should be measured in more populations for a possible implementation as a biomarker of schizophrenia.

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.

Several studies have proposed that cocoa products-enriched in flavonoids reduce anxiety and depressive symptoms. (-)-Epicatechin (Epi), a flavonoid present in high concentration in cocoa, has been associated with many dark chocolate effects and has been postulated as an exercise mimetic. Physical exercise is used as an adjuvant treatment for many depressive patients. This study aimed to evaluate the impact of Epi on resilience in depression-like behavior in a murine model. Male mice were randomly selected and divided into four groups (n = 8/group). Beginning at the age of 8-9 weeks, the mice were subjected to Chronic Mild Stress (CMS) and/or treatment Epi for five weeks. Epi was administered by oral gavage twice daily/5 weeks. The control group was housed in conditions without stress and Epi treatment. Depressive behavior was evaluated by sucrose preference and open field tests. Interestingly, Epi reduced anhedonia and anxiogenic behavior in the murine stress model. These results suggest that Epi induces resilience to stress-induced depression. Furthermore, our findings propose that muscles respond to Epi treatment according to their type of metabolism and that kynurenine aminotransferases (KATs) could play a role in modulating this response.

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.

Schizophrenia is a debilitating mental illness. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in individuals with schizophrenia have been inconsistent across studies. We performed a meta-analysis to evaluate oxytocin levels in plasma, serum and cerebrospinal fluid to see if there are statistically different concentrations between individuals with schizophrenia and the comparison group. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Following the inclusion and exclusion criteria, 14 studies were included in the meta-analysis. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using the Comprehensive Meta-analysis software with the standardized mean difference (SMD) and 95% confidence intervals (CIs). Serum oxytocin levels in individuals with schizophrenia were significantly lower than that in comparison group (SMD = - 1.74, 95% CI = - 3.22 to - 0.26, p = 0.02) but cerebrospinal fluid oxytocin levels in individuals with schizophrenia were significantly higher than those in the comparison group (SMD = 0.55, 95% CI = 0.05 to 1.04, p = 0.03). Our results suggest that oxytocin levels in cerebrospinal fluid are increased in individuals with schizophrenia but decreased in serum. Therefore, the oxytocin system dysregulation may play a role in the pathophysiology of schizophrenia and it should be measured in more populations for a possible implementation as a biomarker of schizophrenia.

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

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

Patients with substance use disorders (SUD) are at high risk to die by suicide. So far, the neurobiology of the suicide-SUD association has not been elucidated. This study aimed to identify potential pharmacological targets among hub genes from brain gene co-expression networks of individuals with SUD in a suicidal and non-suicidal context. Post-mortem samples from the prefrontal cortex of 79 individuals were analyzed. Individuals were classified into the following groups: suicides with SUD (n = 28), suicides without SUD (n = 23), nonsuicides with SUD (n = 9), nonsuicides without SUD (n = 19). Gene expression profiles were evaluated with the Illumina HumanHT-12 v4 array. Co-expression networks were constructed in WGCNA using the differentially expressed genes found in the comparisons: (a) suicides with and without SUD and (b) nonsuicides with and without SUD. Hub genes were selected for drug-gene interaction testing in the DGIdb database. Among drugs interacting with hub genes in suicides we found MAOA inhibitors and dextromethorphan. In the nonsuicide individuals, we found interactions with eglumegad and antipsychotics (olanzapine, clozapine, loxapine). Modafinil was found to interact with genes in both suicides and nonsuicides. These drugs represent possible candidate treatments for patients with SUD with and without suicidal behavior and their study in each context is encouraged.

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.

A genetic component is accepted in the etiology of the glioma. Evidence from candidate genes studies and GWAS reveal that CCDC26 gene could increase the risk of glioma. We performed a systematic review and up-to-date meta-analysis to explore if polymorphisms of CCDC26 gene (rs891835, rs6470745, and rs55705857) may be a susceptibility factor in developing glioma. An online search in PubMed, Web of Science, and SCOPUS up to September 2018 was performed. The pooled odds ratios were evaluated by fixed effects model and random effects model. Analyses of the overall sample and ethnic sub-groups were performed. In all the analyses, the allelic, additive, dominant, and recessive models were used. We found an association between all polymorphisms evaluated and an increased risk for glioma in the overall population in all the models studied. In sub-group analysis, we found that rs891835 and rs6470745 increased the risk of glioma in Europeans and Caucasians. On the other hand, the rs891835 polymorphism did not reveal any statistical association in Chinese population. Taken into consideration the limitations of this study, the present findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma. Furthermore, it is possible that the involvement of CCDC26 variants depends on ethnicity. However, we recommend to perform further studies to have conclusive outcomes.

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.

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.

Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group of neurons located in the lateral hypothalamus and adjacent perifornical area, which send their projections to the mesolimbic dopaminergic (DAergic) system including ventral tegmental area and nucleus accumbens (NAc), where orexin receptors are expressed. NAc plays a central role in reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1 (D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate G-protein-coupled receptors, orexin-receptor type-1 (Orx1R) and type-2 (Orx2R). Orexin receptor signaling is involved in behaviors such as motivation and addiction. Orexin-containing neurons modulate DAergic activity that is key in synaptic plasticity induced by addictive drugs. However, the effect of OrxA on expression and content of DAergic receptors in NAc is unknown. The purpose of this study was to investigate whether OrxA can alter gene expression and protein levels of D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis and protein levels by western blot in rats. The results show that intracerebroventricular (i.c.v.) injection of OrxA increases both gene transcription and protein content of D2R but fails to modify D1R. This effect was also confirmed with OrxA infusion in NAc/Shell. Our results demonstrate for the first time that OrxA induces up-regulation of gene and protein of D2R in NAc. These findings support the hypothesis that OrxA modulates the DAergic transmission and this may serve to understand how orexin signaling enhances DA responses at baseline conditions and in response to psychostimulants.

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.

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.

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.