Suicide is defined as the act of a person attempting to take their own life by causing death. Suicide is a complex phenomenon that is influenced by a multitude of factors, including psychosocial, cultural, and religious aspects, as well as genetic, biochemical, and environmental factors. From a biochemical perspective, it is crucial to consider the communication between the endocrine, immune, and nervous systems when studying the etiology of suicide. Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines, hormones, and neurotransmitters. These humoral signals, when present in optimal quantities, are responsible for maintaining physiological homeostasis, including mood states. Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance, thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior. This review provides an integrative perspective about the neurochemical, immunological, and endocrinological disturbances associated with suicidal behavior, with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.

The World Health Organization and the Global Burden of Disease study estimate that almost 800 000 people die from suicide yearly. The role of non-traditional risk factors such as climate and high-altitude exposure are poorly understood.

This study aims to determine a potential relationship between altitude exposure and suicide rates among 221 cantons located at different altitudes ranging from 0 to 4300 m.

We conducted an 11-year, country-wide, population-based analysis on age- and gender-standardised suicide rates in Ecuador, based on the official data from the National Institute of Statistics, using all available self-harm death codes (ICD-10 codes X60-X84).

A total of 11 280 cases of suicide were reported during 2011-2021. Suicide rates were higher among men (11.48/100 000). In terms of elevation, suicide rates were significantly higher among people from high-altitude cantons (3.7/100 000) versus those from low-altitude cantons. When applying the International Society Mountain Medicine categorisation, suicide rates were significantly higher at moderate- (4.3/100 000), high- (3.6/100 000) and very-high-altitude cantons (4.4/100 000) when compared with low-altitude locations (2.5/100 000).

Ecuador is one of the few countries that has a vast range of cantons located at different altitudes. We found that living at higher elevations is positively associated with greater suicide rates. Although the rates are significantly greater as elevation increases, a clear linear relationship is not apparent, likely because of the interplay of socioeconomic factors, including urbanicity. The effect of chronic hypobaric hypoxia on mood cannot be ruled out, although the existence of causal mechanisms remains to be elucidated.

Several studies involving various suicidal phenotypes based on the strategy of the search of genome-wide associations with single nucleotide polymorphisms have been performed recently. These studies need to be generalized.

To systematize the findings of a number of genome-wide association studies (GWAS) for suicidal phenotypes, annotate the identified markers, analyze their functionality, and possibly substantiate the hypothesis holding that these phenotypes reflect a nonspecific set of gene variants that are relevant as relates to stress-vulnerability as a key endophenotype of suicidal behavior (SB).

A search on the PubMed and related resources using the combinations "suicide AND GWAS" and "suicidal behavior AND GWAS" was performed. It yielded a total of 34 independent studies and meta-analyses.

For the 10 years since such studies emerged, they have undergone significant progress. Estimates of the SNP heritability of SB in some cases are comparable with estimates of heritability based on the twin method. Many studies show a high genetic correlation with the genomic markers of the most common mental disorders (depression, bipolar disorder, schizophrenia, post-traumatic stress disorder). At the same time, a genomic architecture specific to SB is also encountered. Studies utilizing the GWAS strategy have not revealed any associations of SB with candidate genes that had been previously studied in detail (different neurotransmitters, stress response system, polyamines, etc.). Frequently reported findings from various studies belong in three main groups: 1) genes involved in cell interactions, neurogenesis, the development of brain structures, inflammation, and the immune responses; 2) genes encoding receptors for neurotrophins and various components of the intracellular signaling systems involved in synaptic plasticity, embryonic development, and carcinogenesis; and 3) genes encoding various neuro-specific proteins and regulators.

In general, GWAS in the field of suicidology mainly serve the purpose of a deeper understanding of the pathophysiology of suicidal behavior. However, they also demonstrate growing capability in terms of predicting and preventing suicide, especially when calculating the polygenic risk score among certain populations (psychiatric patients) and in combination with tests of different modalities. From our point of view, there exists a set of markers revealed by the GWAS strategy that seems to point to a leading role played by stress vulnerability, an endophenotype that is formed during early development and which subsequently comes to play the role of key pathogenetic mechanism in SB.

This study aims to identify the variables that influence the suicidal tendency of women who are married, have had a relationship or are currently in a relationship in Turkey.

This study uses cross-sectional data from the 2014 Hacettepe University Institute of Population Studies National Research on Domestic Violence Against Women in Turkey. Data from 6,458 women between the ages of 15 and 49 were analyzed in this dataset. Binary logistic regression was used to determine the factors influencing women's suicidal tendencies.

Based on the analysis's findings, age, education level, health status, number of children, the sector in which the spouse/partner works, the drinking status of the spouse/partner, the situation where the spouse/partner fights with another man in a way that involves physical violence, the cheating status of the spouse/partner, the controlling behaviour of the spouse/partner, exposure to various types of violence by both the spouse/partner and someone other than the partner, and the household income level variables were found to be associated with the suicidal tendency of women.

Prioritizing women who are, in particular, between the ages of 15 and 24, live in the south of Turkey, have a high school education, are in poor health, are childless, have low household incomes, live with an unemployed spouse or partner, and are exposed to various forms of violence from their partner or other sources can be achieved more effective results in reducing and preventing women's suicidal behaviors.

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4, SAT-1, TPH-2, ANKK1, GSHR, SCARA50, RGS10, STK33, COMT, and FKBP5. This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.

Suicide is an important public-health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long-distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR-16-5p, miR-19a-3p, miR-34c-5p, miR-17-5p, miR-4286, miR-26b-5p, miR-381-3p, and miR-4516) miR-19a-3p and miR-4516 reached statistical significance with p-values of 0.0408 and 0.0168, respectively. Mir-4516 and miRNA-19a-3p have been previously studied in suicide, and target SLC6A4 and TNF-α expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential.

Suicide is a significant public health issue and a major cause of death in all ages worldwide. Previous studies have shown the involvement of genetics in suicidal behaviour. This study aimed to assess the role of the genetic variants of the serotonin transporter genes (5HTTLPR, SLC6A4 intron 2) and receptor gene (5HTR2AT102C) in individuals who died of suicide. The study compares the serum levels of serotonin between the cases and controls.

We conducted a case control study with 120 cases and 126 controls. Socio-economic details of the subjects were collected using a semi-structured proforma and psychological autopsy was used to collect details of medical and other clinical conditions. Blood was drawn after taking informed consent and serum levels of serotonin were estimated by ELISA. Genotyping was performed using appropriate primers followed by polymerase chain reaction (PCR) and a restriction fragment length polymorphism (RFLP).

Mean age was 32.59 ± 12.58 for cases and 33.64 ± 9.78 for controls. The risk associated LL genotype of 5HTTLPR was higher among cases. The heterozygous 12/10 genotype of SLC6A4 intron 2 polymorphism was increased among controls. Serum levels of serotonin were lower among cases. Variant genotypes of all the 3 polymorphisms showed significant interaction (OR= 39.26) indicating that this model may increase suicidal tendency.

The findings of this study suggest that low serum levels of serotonin and two variants of the serotonin gene may influence suicide behaviour in a south Indian population.

Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér's V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér's V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death.

We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis.

PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10^-4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10^-7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents.

We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.

Mental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder, and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists, and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family toward drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, the structural comparison of ADRA2B, HTR1A, and other members of GPCRs related to mental disorders is performed.

Suicide is a multifaceted and poorly understood clinical outcome, and there is an urgent need to advance research on its phenomenology and etiology. Epidemiological studies have demonstrated that suicidal behavior is heritable, suggesting that genetic and epigenetic information may serve as biomarkers for suicide risk. Here we systematically review the literature on genetic and epigenetic alterations observed in phenotypes across the full range of self-injurious thoughts and behaviors (SITB). We included 577 studies focused on genome-wide and epigenome-wide associations, candidate genes (SNP and methylation), noncoding RNAs, and histones. Convergence of specific genes is limited across units of analysis, although pathway-based analyses do indicate nervous system development and function and immunity/inflammation as potential underlying mechanisms of SITB. We provide suggestions for future work on the genetic and epigenetic correlates of SITB with a specific focus on measurement issues.

Suicide is multifactorial and polygenic phenotype, affected by environmental and genetic factors. Among epigenetic mechanisms, miRNAs have been studied, but so far no very concise results exist. To overcome limitations of candidate miRNA and whole genome sequencing approaches, we created an in silico analysis algorithm that would help select the best suitable miRNAs that target the most interesting genes associated with suicidality. We used databases/web algorithms DIANA microT, miRDB, miRmap, miRWalk, and TargetScan and candidate genes SLC6A4, HTR1A, BDNF, NR3C1, ZNF714, and NRIP3. Based on a prediction algorithm, we have chosen miRNAs that are targeting regulation of the genes listed, and are at the same time being expressed in the brain. The highest ranking scores were obtained for hsa-miR-4516, hsa-miR-3135b, hsa-miR-124-3p, hsa-miR-129-5p, hsa-miR-27b-3p, hsa-miR-381-3p, hsa-miR-4286. Expression of these miRNAs was tested in the brain tissue of 40 suicide completers and controls, and hsa-miR-4516 and hsa-miR-381-3p showed a trend for statistical significance. We also checked the expression of the target genes of these miRNAs, and for NR3C1 expression was lower in suicide completers compared to controls, which is in accordance with the available literature results. To determine the miRNAs that are most suitable for further suicidality research, more studies, combining in silico analysis and wet lab experiments, should be performed.

Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent.

To quantify this risk using meta-analysis and identify potential effect modifiers.

A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes.

Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50-3.53) and attempt suicide (RR = 1.76, 95% CI 1.58-1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death.

The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD.

The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive-compulsive disorder (OCD).

The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke's R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke's R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke's R2 = 4.91%, OR = 1.53, p = 0.043).

The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders.

Psychiatric disorders, including suicide, are complex disorders that are affected by many different risk factors. It has been estimated that genetic factors contribute up to 50% to suicide risk. As the candidate gene approach has not identified a gene or set of genes that can be defined as biomarkers for suicidal behaviour, much is expected from cutting edge technological approaches that can interrogate several hundred, or even millions, of biomarkers at a time. These include the '-omic' approaches, such as genomics, transcriptomics, epigenomics, proteomics and metabolomics. Indeed, these have revealed new candidate biomarkers associated with suicidal behaviour. The most interesting of these have been implicated in inflammation and immune responses, which have been revealed through different study approaches, from genome-wide single nucleotide studies and the micro-RNA transcriptome, to the proteome and metabolome. However, the massive amounts of data that are generated by the '-omic' technologies demand the use of powerful computational analysis, and also specifically trained personnel. In this regard, machine learning approaches are beginning to pave the way towards personalized psychiatry.

In psychiatry, compared to other medical fields, the identification of biological markers that would complement current clinical interview, and enable more objective and faster clinical diagnosis, implement accurate monitoring of treatment response and remission, is grave. Current technological development enables analyses of various biological marks in high throughput scale at reasonable costs, and therefore 'omic' studies are entering the psychiatry research. However, big data demands a whole new plethora of skills in data processing, before clinically useful information can be extracted. So far the classical approach to data analysis did not really contribute to identification of biomarkers in psychiatry, but the extensive amounts of data might get to a higher level, if artificial intelligence in the shape of machine learning algorithms would be applied. Not many studies on machine learning in psychiatry have been published, but we can already see from that handful of studies that the potential to build a screening portfolio of biomarkers for different psychopathologies, including suicide, exists.

Background: Genetics and environment both are critical in autism spectrum disorder (ASD), but their interaction (G × E) is less understood. Numerous studies have shown higher incidence of stress exposures during pregnancies with children later diagnosed with ASD. However, many stress-exposed mothers have unaffected children. The serotonin transporter (SERT) gene affects stress reactivity. Two independent samples have shown that the association between maternal stress exposure and ASD is greatest with maternal presence of the SERT short (S)-allele (deletion in the promoter region). MicroRNAs play a regulatory role in the serotonergic pathway and in prenatal stress and are therefore potential mechanistic targets in this setting. Design/methods: We profiled microRNA expression in blood from mothers of children with ASD, with known stress exposure during pregnancy. Samples were divided into groups based on SERT genotypes (LL/LS/SS) and prenatal stress level (high/low). Results: Two thousand five hundred mature microRNAs were examined. The ANOVA analysis showed differential expression (DE) of 119 microRNAs; 90 were DE in high- vs. low-stress groups (stress-dependent). Two (miR-1224-5p, miR-331-3p) were recently reported by our group to exhibit stress-dependent expression in rodent brain samples from embryos exposed to prenatal stress. Another, miR-145-5p, is associated with maternal stress. Across SERT genotypes, with high stress exposure, 20 significantly DE microRNAs were detected, five were stress-dependent. These microRNAs may be candidates for stress × SERT genotype interactions. This is remarkable as these changes were from mothers several years after stress-exposed pregnancies. Conclusions: Our study provides evidence for epigenetic alterations in relation to a G × E model (prenatal maternal stress × SERT gene) in ASD.

Background: Given that approximately 70% of miRNAs in the body are neuronal, we critically assessed current studies on miRNAs and suicidal behavior. Materials & Methods: To further define the role of miRNAs in suicide, we searched for studies on extracellular vesicles (exosomes) because miRNAs are particularly enriched in exosomes. miRNAs also have important physiological roles, and they can cross the blood-brain barrier and participate in cell-to-cell communication with both nearby and distant cells. Results & Conclusion: This critical assessment suggests that several miRNAs can be closely related to neurophysiology, suicidal behavior, and psychiatric disorders. However, clear overlap is poor due to either different methodologies applied or to molecular differences between suicidal behaviors and studied psychiatric disorders.

Patients with schizophrenia are at a higher risk for suicide compared with the general population. Dopamine beta-hydroxylase (DβH) plays a key role in the conversion of dopamine to norepinephrine, which is related to suicidal behavior and cognitive regulation.

To examine whether there is the effect of DβH 5'-insertion/deletion (Ins/Del) polymorphism on cognitive performance in suicide attempters with chronic schizophrenia.

This polymorphism was detected in 114 suicide attempters and 617 non-suicide attempters with chronic schizophrenia. Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

The allelic and genotypic frequencies of this polymorphism between two groups did not differ after controlling for covariates (both, p > .05). There were no differences in RBANS scores between two groups after adjusting for covariates (all, p > .05). However, based on the genotype grouping in suicide attempters and non-attempters, the attention score significantly differed after adjusting for covariates (both, p < .05). Further analysis indicated that this polymorphism was associated with attention score in suicide attempters (p < .05), but not in non-suicide attempters (p > .05).

DβH 5'-Ins/Del polymorphism was not a risk locus of suicide attempters, but it was implicated in attention regulation in suicide attempters with chronic schizophrenia.

The association between ambient air pollutants exposure and suicidal ideation (SI) has rarely been explored, especially in Chinese population. Therefore, we aimed to investigate the long-term effects of ambient air pollutants on SI among a Chinese rural population.

We recruited 29997 participants from the Henan Rural Cohort study in 2016-2017. SI was evaluated by using the ninth item of the Patient Health Questionnaire-9 (PHQ-9) in the baseline survey. We adopted a satellite-based spatiotemporal model to estimate participants' exposure to particulate matters (PMs) (PM with an aerodynamic diameter ≤1 μm (PM1), ≤2.5 μm (PM2.5) or ≤10 μm (PM10), respectively) and nitrogen dioxide (NO2), and then calculated the 3-year average concentrations of the four pollutants. We used logistic regression models to explore the association between long-term exposure to ambient air pollutants and SI. In addition, we conducted several stratified analyses to examine effect modification of selected factors.

The odds ratios (95% confidence intervals [CI]) of SI in response to each 1 μg/m3 increase in PM1, PM2.5, PM10 and NO2 concentrations were 1.08 (1.01, 1.15), 1.10 (1.02, 1.19), 1.05 (1.01, 1.09) and 1.12 (1.04, 1.21), respectively. Individuals exposed to PM1, PM2.5, PM10 or NO2 concentrations in the fourth quartile had a 1.36-fold (95%CI: 1.08, 1.72), 1.69-fold (95%CI: 1.05, 2.72), 1.49-fold (95%CI: 1.09, 2.05) or 1.71-fold (95%CI: 1.15, 2.85) risks of SI, compared to the ones with corresponding air pollutants in the first quartile. Besides, the risks of SI increased with the quartiles of air pollutants (PM1: Ptrend = 0.002, PM2.5: Ptrend = 0.003, PM10: Ptrend = 0.010, NO2: Ptrend = 0.010). Stratified analyses suggested that males, highly educated participants, ever-drinkers and people aged range 36-64 years were more vulnerable to the adverse effects of air pollutants.

This study provided evidence for the long-term effects of ambient PMs and NO2 on SI in rural Chinese adults, particularly for males, highly educated participants, ever-drinkers and people aged range 36-64 years.

We examined the extent to which genetic factors shared across generations, measured covariates, and environmental factors associated with parental suicidal behavior (suicide attempt or suicide) account for the association between parental and offspring suicidal behavior. We used a Swedish cohort of 2,762,883 offspring born 1973-2001. We conducted two sets of analyses with offspring of half- and full-siblings: (1) quantitative behavior genetic models analyzing maternal suicidal behavior and (2) fixed-effects Cox proportional hazard models analyzing maternal and paternal suicidal behavior. The analyses also adjusted for numerous measured covariates (e.g., parental severe mental illness). Quantitative behavior genetic analyses found that 29.2% (95% confidence interval [CI], 5.29, 53.12%) of the intergenerational association was due to environmental factors associated with exposure to maternal suicidal behavior, with the remainder due to genetic factors. Statistical adjustment for parental behavioral health problems partially attenuated the environmental association; however, the results were no longer statistically significant. Cox hazard models similarly found that offspring were at a 2.74-fold increased risk [95% CI, 2.67, 2.83]) of suicidal behavior if their mothers attempted/died by suicide. After adjustment for familial factors and measured covariates, associations attenuated but remained elevated for offspring of discordant half-siblings (HR, 1.57 [95% CI, 1.45, 1.71]) and full-siblings (HR, 1.62 [95% CI, 1.57, 1.67]). Cox hazard models demonstrated a similar pattern between paternal and offspring suicidal behavior. This study found that the intergenerational transmission of suicidal behavior is largely due to shared genetic factors, as well as factors associated with parental behavioral health problems and environmental factors associated with parental suicidal behavior.

Few quantitative behavior genetic studies have examined why psychopathology is associated with suicide attempt (SA) and self-harm (SH) in adolescence. The present study analyzed data from the Child and Adolescent Twin Study in Sweden to examine the extent to which genetic and environmental factors explain SA/SH and its association with psychopathology in childhood, an often-cited risk factor of subsequent SA/SH. When children were 9 or 12 years old (n = 30,444), parents completed the Autism-Tics, AD/HD and other Comorbidities Inventory (Larson et al., 2010) regarding their children's psychiatric problems as part of an ongoing, longitudinal study. At age 18 years (n = 10,269), adolescents completed self-report questionnaires, including SA/SH assessments. In a bifactor model of childhood psychopathology, a general factor of psychopathology was a statistically significant predictor of adolescent SA/SH at a higher magnitude (β, 0.25, 95% confidence interval [CI; 0.15, 0.34] for suicide attempt), as compared with specific factors of inattention, impulsivity, oppositional behavior, and anxiety/emotion symptoms. Quantitative genetic modeling indicated that the additive genetic influences on the general factor accounted for the association with each outcome (β, 0.24, 95% CI [0.13, 0.34] for suicide attempt). The results remained virtually identical when we fit a higher order factors model. Two additional outcomes demonstrated comparable results. The results extend current literature by revealing the shared genetic overlap between general psychopathology during childhood and adolescent SA/SH. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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.

Studies suggest aberrant DNA methylation in victims of suicide. Recently, DNA methylation profiles have been developed for determining "epigenetic age," which is the most accurate estimate of biological age. Subsequently, two refined measures of epigenetic age acceleration have been expanded for blood samples as intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively). IEAA involves pure epigenetic aging independent of blood cell composition, whereas EEAA involves immunosenescence in association with blood cell composition.

We investigated epigenetic age acceleration using two independent DNA methylation datasets: a brain dataset from 16 suicide completers and 15 non-psychiatric controls and a blood dataset compiled using economical DNA pooling technique from 56 suicide completers and 60 living healthy controls. In the blood dataset, we considered IEAA and EEAA, as well as DNA methylation-based blood cell composition.

There was no significant difference in universal epigenetic age acceleration between suicide completers and controls in both brain and blood datasets. Blood of suicide completers exhibited an increase in EEAA, but not in IEAA. We additionally found that suicide completers had more natural killer cells but fewer granulocytes compared to controls.

This study provides novel evidence for accelerated extrinsic epigenetic aging in suicide completers and for the potential application of natural killer cells as a biomarker for suicidal behavior.

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.

Genetics is a major etiological contributor to autism spectrum disorder (ASD). Environmental factors, however, also appear to contribute. ASD pathophysiology due to gene x environment is also beginning to be explored. One reason to focus on environmental factors is that they may allow opportunities for intervention or prevention.

Herein, we review two such factors that have been associated with a significant proportion of ASD risk, prenatal stress exposure and maternal immune dysregulation. Maternal stress susceptibility appears to interact with prenatal stress exposure to affect offspring neurodevelopment. We also explore how maternal stress may interact with the microbiome in the neurodevelopmental setting. Additionally, understanding of the impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles. This might also be interrelated with maternal stress exposure. Animal models have been developed to explore pathophysiology targeting each of these factors.

We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related to these interactions, and we are beginning to explore potential mitigating factors. Continued growth in understanding of these mechanisms may ultimately allow for the identification of multiple potential targets for prevention or intervention for this subset of environmental-associated ASD cases.

The article entitled “Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery”, by Da-Yong Lu, Peng- Peng Zhu, Hong-Ying Wu, Nagendra Sastry Yarla, Bin Xu, Jian Ding, Ajit Varki and Ting-Ren Lu, has been retracted on the request of the co-authors, Dr. Ajit Varki, Dr. Nagendra Sastry Yarla and Dr. Jian Ding available at: Cent Nerv Syst Agents Med Chem 2019; 19(1): 15-23. http://www.eurekaselect.com/169003/article. The Corresponding Author Dr. Da-Yong Lu has included the names of the co-authors, Dr. Ajit Varki, Dr. Nagendra Sastry Yarla and Dr. Jian Ding without their consent and the manuscript has been published in the journal, Central Nervous System Agents in Medicinal Chemistry (CNSAMC). Kindly see Bentham Science Policy on Article retraction at the link given below: (https://benthamscience.com/journals/central-nervous-system-agents-in-medicinal-chemistry/author-guidelines/) Submission of a manuscript to the respective journals implies that all authors have read and agreed to the content of the Copyright Letter or the Terms and Conditions. As such, this article represents a severe abuse of the scientific publishing system. Bentham Science Publishers takes a very strong view on this matter and apologizes to the readers of the journal for any inconvenience this may cause.

Recently, several studies using transcranial sonography (TCS) have demonstrated reduced echogenicity of the mesencephalic midline in unipolar depression and patients with comorbid depression and Parkinson disease (PD). However, there is no consensus on the conclusion that raphe nuclei (RN) hypoechogenicity is associated with depression in PD. The methods used in previous studies lack quantitative and objective indicators to some extent; therefore, the present study used the level of platelet 5-hydroxytryptamine (5-HT) as an objective indicator of depression. Additionally, the reason for the reduced echogenicity of the brainstem raphe is still unclear.

The purpose of the present study was to assess the correlation between alterations in RN echogenicity and depressive symptoms in patients with PD using transcranial sonography (TCS). This information could provide a meaningful clinical reference for the antidiastole between depressive symptoms in PD and unipolar depression in patients with PD in whom depressive symptoms occur before motor symptoms.

TCS was performed in patients with PD, patients with PD and depression, patients with depression and no PD, and healthy controls. Using the red nucleus as a reference, the RN was rated from grades 0 to 1 (grade 0: invisible, slightly echogenic, or interrupted RN; grade 1: hyperechogenicity in the RN observed as a continuous line).

The rate of abnormal RN (grade 0) was found to be 16.67% in patients with PD (5/30) and 14.29% in healthy controls (4/28). The presence of abnormal RN was significantly higher (χ = 15.983, P < .05) in patients with depression and PD (40%, 12/30) and in patients with depression only (58.33%, 14/24) than in those without depression and healthy controls. No correlation was found between RN changes and depression severity (P > .05). There were no statistical differences in the concentration of platelet serotonin among the 4 groups (P > .05).

TCS of the mesencephalic midline may be useful for detecting depression, which is an early symptom of PD. However, further neuropathological studies are needed to understand the principles underlying the use of platelet serotonin as a peripheral biomarker, as well as the connection between PD and depression.

While genetic factors are a major etiological contributor to autism spectrum disorder (ASD), evidence also supports a role for environmental factors. Herein, we will discuss two such factors that have been associated with a significant proportion of ASD risk: prenatal stress exposure and maternal immune dysregulation, and how sex and gender relate to these factors.

Recent evidence suggests that maternal stress susceptibility interacts with prenatal stress exposure to affect offspring neurodevelopment. Additionally, understanding of the impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles. Animal models have been developed to explore pathophysiology targeting both of these factors, with limited sex-specific effects observed. While prenatal stress and maternal immune dysregulation are associated with ASD, most cases of these prenatal exposures do not result in ASD, suggesting interaction with multiple other risks. We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related to these interactions, as well as potential mitigating factors. Sex differences of these risks have been understudied but are crucial for understanding the higher prevalence of ASD in boys. Continued growth in understanding of these mechanisms may ultimately allow for the identification of multiple potential points for prevention or intervention, and for a personalized medicine approach for this subset of environmental-associated ASD cases.

The risk of suicide is greatly increased in individuals with schizophrenia. Previous research has identified several potential risk factors for suicidal behavior in schizophrenia, although their ability to independently predict suicide is limited. The objective of this review was to systematically analyze and identify the interaction between the proposed risk factors in the literature that may predict suicidal behavior in schizophrenia. Articles that explored suicidal behavior and suicide risk in schizophrenia that were published between 1980 and August of 2015, indexed in PubMed, MEDLINE, and Scopus were systematically reviewed. Many studies proposed a range of biopsychosocial risk factors that may independently lead to suicide in schizophrenia. These risk factors appear to be mainly related to stress, a history of suicidal behavior, and psychotic symptoms. It is clear, however, that many of these factors do not act independently and in fact require the reciprocal interaction of several of them to pose a risk for suicide in schizophrenia. Independently, the power of many risk factors to predict suicide is limited. Future studies should continue to adopt a multidimensional approach by considering the interaction of several factors in assessing the risk for suicide in schizophrenia.

To prevent suicide, a nationwide important issue in Korea, understanding its etiology is essential. This study aimed to delineate the risk factors for suicidal behavior in mood disorder patients in Korea.

216 patients with mood disorders were recruited. We measured suicidal ideation (SI) and suicide attempt (SA) history and the association of six gene polymorphisms with SB: COMT (rs4680), HTR1A (rs6295), TPH1 (rs1800532), BDNF (rs6265), SLC1A3 (rs2269272), and SLC1A2 (rs4755404).

Patients in the high-SI and SA groups reported more severe depressive, hopelessness, and anxiety symptoms and lower resilience and used less social support-seeking coping than those in the non-significant SI and non-SA groups. Multivariate logistic analysis revealed that depressive disorder, depressive symptoms, poor social support, and less social support-seeking coping were significant independent predictors of suicidal ideation. After adjustment for covariates, age, alcohol consumption, and the rs4680 AA genotype in the COMT gene were associated with suicide attempt.

The modest sample size and a relatively few candidate genes are limitations of the study. In addition, there is no normal control group and the retrospective evaluation of SA limits the interpretation of the causal relationship with factors affecting SA.

Suicidal behavior in Korean patients with mood disorders may be associated with younger age, alcohol consumption, depressive symptoms, poor social support, less social support-seeking coping, and the COMT rs4680 Met/Met genotype.

Suicide is a devastating public health issue that imposes severe psychological, social, and economic burdens not only for the individuals but also for their relatives, friends, clinicians, and the general public. Among the different suicidal behaviors, suicide completion is the worst and the most relevant outcome. The knowledge of biological etiopathological mechanisms involved in suicide completion is limited. Hitherto, no objective markers, either alone or in combination, can reliably predict who will complete a suicide. However, such parameters are strongly needed to establish and optimize prediction and prevention. We introduce here a novel ideation-to-completion framework in suicide research and discuss the problems of studies aiming at identifying and validating clinically useful markers. The male gender is a specific risk factor for suicide, which suggests that androgen effects are implicated in the transition from suicidal ideation to suicide completion. We present multiple lines of direct and indirect evidence showing that both an increased prenatal androgen load (with subsequent permanent neuroadaptations) and increased adult androgen activity are involved in suicide completion. We also review data arguing that modifiable maternal behavioral traits during pregnancy contribute to the offspring's prenatal androgen load and increase the risk for suicide completion later in life. We conclude that in utero androgen exposure and adult androgen levels facilitate suicide completion in an synergistic manner. The androgen model of suicide completion provides the basis for the development of novel predictive and preventive strategies in the future.

Genetic association studies have linked suicide behavior with genes encoding transporters of monoamine. Variants in the vesicular monoamine transporter 1 (VMAT1) have been previously shown to be associated with several psychiatric disorders including schizophrenia and bipolar disorder. However, their association with suicide behavior has not been explored. In the present study, we genotyped three single-nucleotide polymorphisms (rs2270637, rs1390938, and rs2279709) within this gene in 100 individuals who attempted suicide, 236 suicide victims, and 300 control subjects without any history of psychiatric disorders or suicide ideation. We demonstrated no difference in genotype, allele, or haplotype frequencies of theses single-nucleotide polymorphisms between the study groups. Consequently, contribution of VMAT1 in risk of psychiatric disorders might be independent of suicide behavior. Future studies with larger sample sizes are needed to confirm our results.

Life events are series of events that disrupt a person's psychological equilibrium and may enhance the development of a disorder such as suicide. Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicide. However, there has been no study about the association between three 5-HTR2A gene polymorphisms, A1438G (rs6311), T102C (rs6313) and C1354T (rs6314), suicide, stressful life, and loss events in a same time.

Relatives of 191 suicide victims were interviewed using a semi-structured questionnaire designed according to Iranian culture. Venous blood was taken from all subjects for DNA isolation. 5-HTR2A polymorphisms in a total of 191 suicide victims and 218 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-squared and Fisher's exact tests were used to compare genotype and allele frequencies between suicide and control groups. Correction for multiple comparisons was calculated using Bonferroni correction.

There was a significant association between the 102 C/C genotype of 5-HTR2A gene and suicide (к² = 8.700, P = 0.012). Furthermore, we found that suicide victims with a 102 C/C genotype had a significantly higher number of stressful life and loss events (P < 0.05). Genotype and allele distributions of A1438G (rs6311) and C1354T (rs6314) polymorphisms of 5-HTR2A gene showed no differences between suicide victims and control participants and there was no association between genotype distribution and higher number of stressful life and loss events (P > 0.05).

Our results suggest that C102T (rs6313) polymorphism of 5-HTR2A gene may be involved in the susceptibility to suicide, higher number of stressful life and loss events, but A1438G (rs6311) and C1354T (rs6314) polymorphisms of 5-HTR2A gene were not associated with suicide, higher number of stressful life and loss events.

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.

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.

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).

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.

Suicide occurs more often in older than in younger people, but is still one of the leading causes of death in late childhood and adolescence worldwide. This not only results in a direct loss of many young lives, but also has disruptive psychosocial and adverse socio-economic effects. From the perspective of public mental health, suicide among young people is a main issue to address. Therefore we need good insight in the risk factors contributing to suicidal behavior in youth. This mini review gives a short overview of the most important risk factors for late school-age children and adolescents, as established by scientific research in this domain. Key risk factors found were: mental disorders, previous suicide attempts, specific personality characteristics, genetic loading and family processes in combination with triggering psychosocial stressors, exposure to inspiring models and availability of means of committing suicide. Further unraveling and knowledge of the complex interplay of these factors is highly relevant with regard to the development of effective prevention strategy plans for youth suicide.

The main aim of the current study was to investigate epigenetic alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk factors for suicidal behavior. We also aimed to analyze the epigenetic alterations in two different tissues as epigenetic mechanisms are tissue specific. These epigenetic changes may lead to a better prediction of suicidal behavior.

Direct CpG methylation analysis was carried out on genomic DNA from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and from post-mortem brain tissues of nine suicide victims and 11 controls. We used bisulfite pyrosequencing to assess the contributions of six CpG sites including the rs6313 (C102T) site in the first exon of HTR2A in suicide attempters and suicide victims.

DNA methylation analysis did not find a significant difference in CpG methylation between suicide attempters and non-attempters (P=0.759) or between suicide victims and controls (P=0.189). We found a strong positive correlation between CpG methylation levels in blood and saliva (r=0.547, P<0.001).

DNA methylation analysis confirmed that the overall methylation level of HTR2A exon I was around 80% for DNA extracted from saliva and almost 30% in the frontal cortex DNA. The results of this investigation do not support the evidence that methylation analysis of the HTR2A may be useful for investigating the epigenetic factors involved in suicidal behavior.

Suicide affects people from different backgrounds, ethnical groups, socio-economic status and geographical locations. In Latin America, suicide reports arescarce, specially in Andean countries. In Ecuador, very few reports have partially described this phenomenon, nonetheless, estimation of the burden of disease (BoD) hasnever been reported in the country.

A country-wide comparison was performed using the Ministry of Public Health's national databases of overall mortality, Hospital Discharges Database, and the Population Census of the National Institute of Census and Statistics (INEC). The study variables analyzed were age, geographical distribution to provincial level, sex, means of suicide, educational attainment, marital status and mortality. Linear Regression and relative Risk analysis were used to predict outcome and the likelihood that suicide occur among study variables.

In the last 15 years, 13,024 suicides were officially reported. Men were 3 times more likely than women to die by suicide. The overall age-adjusted suicide ratio in Ecuador corresponds to 7.1 per 100,000 per year. The sex-specific rates were 5.3 in women and 13.2 in men. The primary mean of suicide was hanging X70 (51.1%), followed by self-poisoning X68-X69 (35.2%) and firearms X72-X74 (7.6%). Provinces located at higher altitude reported higher rates than those located at sea level (9 per 100,000 vs 4.5 per 100.000). The total economic loss due to suicide was estimated to be $852.6 million during the 15 years' analysis.

This is the first geodemographic study exploring the complete burden of suicide in Ecuador and one of the very few in Latin-America. In the last 15 years of available data, Ecuador ranks above the regional average with an adjusted suicide rate of 7.1 per 100,000 inhabitants. An important finding is that Suicide affects rather younger populations, adding more than 10,000 years of premature years of life lost (YYL) between 2001 and 2015, becoming the first and fourth leading cause of death among adolescent women and men respectively. Suicide affects people from different backgrounds, socioeconomic status and educational attainment. The mean of suicide changed over time showing that gun and pesticides related deaths decreased significantly since 2001, while hanging and suffocation increased in more than 50%.

Low GABA transmission has been reported in suicide, and GABRA6 rs3219151 T allele has been associated with greater physiological and endocrine stress response in previous studies. Although environmental stress also plays a role in suicide, the possible role of this allele has not been investigated in this respect. In our present study effect of rs3219151 of GABRA6 gene in interaction with recent negative life events on lifetime and current depression, current anxiety, as well as lifetime suicide were investigated using regression models in a white European general sample of 2283 subjects. Post hoc measures for phenotypes related to suicide risk were also tested for association with rs3219151 in interaction with environmental stress. No main effect of the GABRA6 rs3219151 was detected, but in those exposed to recent negative life events GABRA6 T allele increased current anxiety and depression as well as specific elements of suicide risk including suicidal and death-related thoughts, hopelessness, restlessness and agitation, insomnia and impulsiveness as measured by the STOP task. Our data indicate that stress-associated suicide risk is elevated in carriers of the GABRA6 rs3219151 T allele with several independent markers and predictors of suicidal behaviours converging to this increased risk.

The aim of this study is to investigate whether a 44-base-pair insertion/deletion polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) is associated with the nursing diagnoses and the achievement of the desired nursing outcomes in inpatients with major depression. Thirty five patients were evaluated. The nursing diagnoses of risk for suicide and imbalanced nutrition are reported less often in homozygotes of the high-expressing gene (L_A). Carriers of the low-expressing genes (L_G or S) have a worse response to interventions which aim to increase low self-esteem, indicating that they may need more intensive care in order to achieve the desired outcome. Genetics in psychiatric nursing could help refine personalized care, however further studies with large sample sizes and multiple gene evaluations are needed.

Several lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its aetiology. We focused on nine genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) which we previously detected as differentially expressed in the cortex of suicide victims compared to controls. We investigated 84 variants within these genes in 495 suicidal subjects (299 completers and 196 attempters) and 1513 controls (109 post-mortem and 1404 healthy). We evaluated associations with: 1) suicidal phenotype; 2) possible endophenotypes for suicidal behaviour. Overall positive results did not survive the correction threshold. However, we found a nominally different distribution of EFEMP1 genotypes, alleles and haplotypes between suicidal subjects and controls, results that were partially replicated when we separately considered the subgroup of suicide completers and post-mortem controls. A weaker association emerged also for PTPRR. Both EFEMP1 and PTPRR genes were also related to possible endophenotypes for suicidal behaviour such as anger, depression-anxiety and fatigue. Because of the large number of analyses performed and the low significance values further replication are mandatory. Nevertheless, neurotrophic gene variants, in particular EFEMP1 and PTPRR, may have a role in the pathogenesis of suicidal behaviour.

The RDoC matrix framework calls for investigation of mental health problems through analysis of core biobehavioral processes quantified and studied across multiple domains of measurement. Critics have raised concerns about RDoC, including overemphasis on biological concepts/measures and disregard for the principle of multifinality, which holds that identical biological predispositions can give rise to differing behavioral outcomes. The current work illustrates an ontogenetic process approach to addressing these concerns, focusing on biobehavioral traits corresponding to RDoC constructs as predictors, and suicidal behavior as the outcome variable.

Data were collected from a young adult sample (N=105), preselected to enhance rates of suicidality. Participants completed self-report measures of traits (threat sensitivity, response inhibition) and suicide-specific processes.

We show that previously reported associations for traits of threat sensitivity and weak inhibitory control with suicidal behavior are mediated by more specific suicide-promoting processes-namely, thwarted belongingness, perceived burdensomeness, and capability for suicide.

The sample was relatively small and the data were cross-sectional, limiting conclusions that can be drawn from the mediation analyses.

Given prior research documenting neurophysiological as well as psychological bases to these trait dispositions, the current work sets the stage for an intensive RDoC-oriented investigation of suicidal tendencies in which both traits and suicide-promoting processes are quantified using indicators from different domains of measurement. More broadly, this work illustrates how an RDoC research approach can contribute to a nuanced understanding of specific clinical problems, through consideration of how general biobehavioral liabilities interface with distinct problem-promoting processes.

Suicide is a common occurrence in psychiatric disorders and is a cause of increased healthcare utilization worldwide. Schizophrenia is one of the most common psychiatric disorders worldwide and posited to be seen in 1% of the population worldwide. Suicide is a common occurrence in schizophrenia with 25%-30% patients with schizophrenia attempting suicide and 8%-10% completing it. There is a need for valid biological markers to help clinicians identify patients with schizophrenia that may be at a risk of suicide and thus help in them receiving better care and interventions at the earliest even before a suicide attempt occurring. There are clear neurobiological changes at a genetic, neuroimaging, and neurochemical level that occurs in patients with schizophrenia that attempt suicide. There is a new theory that postulates neuronal plasticity and neuroprotection to have a role in the biological changes that ensue when suicidal thoughts and feelings occur in patients with schizophrenia. Neurotrophic growth factors like brain-derived neurotrophic factor (BDNF) have been documented to play a role in the protection of neurons and in the prevention of neurobiological changes that may lead to suicide both in schizophrenia and depression. The present paper presents a commentary that looks at the role of BDNF as a protective factor and neurobiological marker for suicide in schizophrenia.