Effects of IL-6/IL-6R axis alterations in serum, plasma and cerebrospinal fluid with the schizophrenia: an updated review and meta-analysis of 58 studies.

Studies investigating the association between IL-6/IL-6R axis and schizophrenia (SZ) susceptibility found inconsistent data. To reconcile the results, a systematic review followed by a meta-analysis was performed to assess the associations. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in July 2022 using electronic databases PubMed, EBSCO, Science Direct, PsychInfo, and Scopus. Study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Fifty-eight studies were identified, including 4,200 SZ patients and 4,531 controls. Our meta-analysis results showed an increase of IL-6 levels in plasma, serum, or CSF and decreased IL-6R levels in serum in patients under treatment. Further studies are needed to better elucidate the correlation between the IL-6/IL-6R axis and the schizophrenia.

The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.

Genes involved in the hypothalamic-pituitary-adrenal axis may be a robust biomarker of psychiatric disorders. Genetic polymorphisms of the SKA2 gene are associated with several behavioral disorders. In this study, we embarked on a systematic search of all possible reports of genetic association with SKA2 and affective disorder, post-traumatic stress disorder, and suicide behavior; the functional consequences of nsSNPs were explored through computational tools with an in silico analysis. Eight eligible articles were included. Our study identified that SKA2 did not show association with risk of Major Depression Disorder. Epigenetic variation at SKA2 mediates vulnerability to Post-Traumatic Stress Disorder. Studies provide strong preliminary evidence that alterations at the SKA2 gene covary with types of suicide behavior, including suicidal ideation, attempts, and completions. Results from in silico analysis predicted that I22S, I22G, I78T, A15L, D18R, R25L, N42I, Y21S, K14I, K14L, and L60R were the most structurally and functionally significant nsSNPs in SKA2. Amino acid conservation analysis revealed that the amino acids were highly conserved and some dissimilarities of mutant type amino acids from wild-type amino acids such as charge, size, and hydrophobicity were observed. In the future, SKA2 gene have the potential to be evaluated as prognostic biomarkers for diagnosis and research.

Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis.

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.

Effect of risperidone on serum IL-6 levels in individuals with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prevalence of Poor Sleep Quality and Associated Factors in Individuals with Rheumatoid Arthritis: A Cross-Sectional Study.

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

Oxytocin levels in individuals with schizophrenia are high in cerebrospinal fluid but low in serum: A systematic review and meta-analysis : Oxytocin and Schizophrenia.

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 role of TaqI, ApaI and BsmI polymorphisms of VDR gene in lumbar spine pathologies: systematic review and meta-analysis.

PURPOSE: The objective of the present meta-analysis was to evaluate the association between TaqI (rs731236), ApaI (rs7975232) and BsmI (rs1544410) polymorphisms of the VDR gene and lumbar spine pathologies such as lumbar disc herniation and lumbar disc degeneration. BACKGROUND: VDR gene polymorphisms have been reported to be associated with an increased risk of lumbar spine pathologies. MATERIALS AND METHODS: A systematic search was performed up to February 2020 using PubMed, EBSCO and Web of Science databases. We used the keywords and combinations "lumbar disc degeneration," "lumbar disc herniation," "lumbar spine pathologies" and "VDR polymorphism." Subsequently, we performed a meta-analysis with the results of the included studies. RESULTS: We found that the TaqI polymorphism was associated with an increased risk of developing lumbar spine pathologies (recessive model OR 1.25, 95% CI 1.01-1.54) and lumbar disc degeneration (allelic model OR 1.26, 95% CI 1.07-1.48; recessive model OR 1.34, 95% CI 1.06-1.69), but not with lumbar disc herniation. Additionally, ApaI was associated with an increased risk of developing lumbar spine pathologies (heterozygous model OR 1.45, 95% CI 1.06-1.98), but not with lumbar disc herniation or lumbar disc degeneration. CONCLUSIONS: Our findings indicate that TaqI and ApaI polymorphisms of the VDR gene are important risk factors for developing lumbar spine pathologies. Moreover, the TaqI polymorphism is a risk factor for lumbar disc degeneration.

Evaluation of leptin levels in serum as a biomarker for suicide behavior: systematic review and meta-analysis.

Objective: We conducted a meta-analysis of case-control studies to determine whether leptin levels in serum contribute to the pathogenesis of suicide behavior.Methods: PubMed, EBSCO and Science Direct databases were used to search for relevant articles published before January 2020. The systematic review included nine case-control studies that measured leptin levels. The standardized mean difference (d) and 95% confidence intervals were calculated in a fixed-effects model and a random-effects model when appropriate.Results: The results of our meta-analysis indicated that individuals with suicide behavior presented reduced levels of leptin (d: -1.80, 95% CI: -2.21 to -01.38 ng/ml, I2 = 0, p(Q) = 0.59). Sensitivity and publication bias analyses confirmed these results.Conclusions: The current meta-analysis suggests that leptin levels might be associated with an increased risk of suicide behavior. However, more studies including larger sample sizes are needed to reach conclusive result.

Evaluation of alexithymia in individuals with chronic pain in a Mexican population: Alexithymia in a Mexican population.

INTRODUCTION: Alexithymia is the difficulty in identifying and describing feelings. Several studies have suggested that chronic pain can be linked to alexithymia. The aims of this study were to determine the presence of alexithymia in a sample of Mexican individuals who attended public health services, to assess if alexithymia is higher in medically ill individuals with pain than in those without pain, and to determine which alexithymia dimensions are more affected by the presence of pain. METHODS: Demographic and clinical features were evaluated in 250 Mexican outpatients of the General Hospital of Comalcalco, Tabasco. Pain was evaluated using the Visual Analogue Scale for Pain Assessment (VAS-P) and alexithymia was evaluated using the Toronto Alexithymia Scale (TAS-20). RESULTS: 38.8% of the sample was identified with probable/definite alexithymia and up to 61.2% of individuals were currently experiencing pain. Individuals with pain exhibited higher scores in the TAS-20 dimensions: difficulty describing feelings (p = 0.02), difficulty identifying feelings (p < 0.001) and higher total TAS-20 score (p < 0.001). Also, Probable/definite alexithymia was more frequently reported in individuals with pain (49% vs. 21.6%, p < 0.001). CONCLUSIONS: Our results show that a large proportion of individuals who attend public health services in a Mexican population present pain. We also identified that pain could be associated with alexithymia, in particular with a difficulty in describing and identifying feelings. An early identification and treatment of alexithymia could help in reducing the clinical burden of chronic pain in Mexican outpatients.

Differences in attitude toward prevention of suicide between nursing and medicine students: A study in Mexican population.

The aim of the present study was to evaluate the attitude toward suicide prevention in medicine and nursing students attending University in south Mexico, considering their family and personal history of suicide. Demographic features and self-reported personal and family history of suicide were evaluated in 355 Mexican students at the Health Sciences School. Their views toward suicide prevention was assessed using the Attitude Toward Suicide Prevention scale. Comparisons between medicine and nursing students were performed, as well as between had or had-not previous personal or family history of suicide. Our results support that nursing students showed the most negative attitude toward suicide prevention. Therefore, training programs and strategies encouraging a better attitude in suicide prevention are necessary to be implemented. It is also necessary to consider cultural, ethnic and family backgrounds of the students/of the population when developing new strategies.

Prevalence for and Factors Associated With Depression and Anxiety Symptoms in Mexican Patients With Rheumatoid Arthritis.

BACKGROUND/OBJECTIVE: It has been suggested that patients with rheumatoid arthritis (RA) often present depression and anxiety. The objective of this study was to estimate the prevalence of depression and anxiety symptoms in Mexican patients with RA and to determine associated factors of depression and anxiety in this population. METHODS: This was a cross-sectional study. We evaluated demographic characteristics, medical comorbidities, substance use, and disease characteristics in 103 patients with RA. Patients were enrolled from March 2016 to August 2017 The prevalence of depression and anxiety was estimated using the Hospital Anxiety and Depression Scale. We calculated the proportion of depression and anxiety symptoms and compared characteristics between groups. Finally, logistic regression model was used to determine the factors associated with depression and anxiety. RESULTS: Depression symptoms were present in 26.2% of patients, whereas anxiety symptoms were present in 16.5% of patients. Presence of hypertension was an associated factor with depression (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.06-9.23; p = 0.03). Low socioeconomic (OR, 3.78; 95% CI, 1.39-10.28; p = 0.009) and high scores of 28-joint Disease Activity Score were associated with anxiety (OR, 3.19; 95% CI, 1.20-8.45; p = 0.02). CONCLUSIONS: Factor related to socioeconomic conditions, comorbid medical conditions, and disease activity were related to the presence of clinical depression and anxiety in Mexican patients with RA, which may have a negative impact in the course and outcome of the disease. We suggest an early identification of depression and anxiety in these patients through an early psychiatric evaluation.

Association between polymorphisms of NOS1, NOS2 and NOS3 genes and suicide behavior: a systematic review and meta-analysis.

The enzyme nitric oxide synthase has been associated with suicide behavior. NOS1, NOS2 and NOS3 genes are implicated in the production of nitric oxide. However, the association between NOS genes and suicide behavior has not yet been established. To assess the association of Nitric Oxide Synthase (NOS) genes and suicide behavior we performed a systematic review a meta-analysis. We searched articles published in three electronic databases, PubMed, Scopus and Web of Sciences, up to February 2019. We used keywords and combinations "NOS", "NOS1", "NOS2", "NOS3" and "suicide". Only articles that met the inclusion criteria were included. To assess the association between NOS genes and suicide behavior we used allelic, dominant and recessive models, as well as homozygous and heterozygous comparisons. The pooled results showed that rs2682826 of Nitric Oxide Synthase 1 gene (NOS1) increased the risk for suicide attempt in the allelic (OR: 1.34; 95 CI: 1.00-1.78), recessive (OR: 1.45; 95 CI:1.06-1.98) and heterozygous (OR: 1.41; 95 CI: 1.09-1.81) models. We found that the rs2682826 of NOS1 could increase the risk for suicide attempt. However, these results should only be taken as exploratory; more studies are necessary to determine the association between NOS genes and suicide behavior.

Genetic Polymorphisms of CCDC26 rs891835, rs6470745, and rs55705857 in Glioma Risk: A Systematic Review and Meta-analysis.

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.

Prevalence and Associated Factors to Depression and Anxiety in Women with Premature Babies Hospitalized in a Neonatal Intensive-Care Unit in a Mexican Population.

PURPOSE: The aims of this study were to investigate the frequency of depression and anxiety in mothers of children hospitalized in a neonatal intensive care unit, and to determine the characteristics associated with depression and anxiety in a sample of Mexican mothers. METHOD: We studied 188 mothers who had premature babies in a neonatal intensive-care. Sociodemographic and clinical characteristics were collected through a face to face interview performed by professional staff. We assessed depression using the Beck Depression Inventory (BDI) and clinical anxiety using the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Clinical anxiety was reported in more than one-third of women (34.0%, n = 64) followed by depression (19.7%, n = 37), while twenty-six women reported both significant depression and anxiety (13.8%). Women with both clinical symptoms were younger, they were more frequently students and were living within extended families. Women who presented only symptoms of depression reported lower educational level (elementary school 29.7%, n = 11). CONCLUSION: Our results show a high incidence of anxiety, depression, and both emotional disorders in Mexican mothers of premature babies hospitalized in a neonatal intensive care unit. Demographic features such as occupation or age may impact the occurrence and severity of joint symptoms of depression and anxiety which should be monitored by the health team and referred to a mental health service.

Association between Polymorphisms of the DRD2 and ANKK1 Genes and Suicide Attempt: A Preliminary Case-Control Study in a Mexican Population.

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

The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis.

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

Differential Alterations of Expression of the Serotoninergic System Genes and Mood-Related Behavior by Consumption of Aspartame or Potassium Acesulfame in Rats.

The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression.

Increased Depressive-like, Anxiety-like, and Perseverative-like Behavior in Binge Eating Model in Juvenile Rats.

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

DNA Methylation of Genes Involved in the HPA Axis in Presence of Suicide Behavior: A Systematic Review.

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.

Gene Expression Analysis in Postmortem Brains from Individuals Who Died by Suicide: A Systematic Review.

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