Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk.

BACKGROUND: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI). METHODS: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA. RESULTS: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI. CONCLUSIONS: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA. LIMITATIONS: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.

[Polymorphisms of OPRM1, OPRK1, DCC genes and non-suicidal self-injuries in adults]. / Polimorfizmy genov OPRM1, OPRK1 i DCC i nesuitsidal'nye samopovrezhdeniya u vzroslykh.

OBJECTIVE: To investigate the associations of OPRM1 gene rs179971, OPRK1 gene rs6473797 and DCC gene rs8084280 polymorphisms with non-suicidal self-injury (NSSI) characteristics and motivations in adults. MATERIAL AND METHODS: A pilot sample included 28 adult patients with history of NSSI (89.3% (n=25) women, median age (Q1-Q3) - 23 (21.25-25) years). Most patients (78.6%, n=20) had a diagnosis of bipolar disorder. NSSI characteristics and motivations were assessed using the Inventory of Statements about Self-Injury (ISAS) scale. The Childhood Trauma Questionnaire (CTQ) was used to control for childhood trauma - one of the most important environmental factors associated with NSSI. The Baratt Impulsivity Scale (BIS) and the Buss-Perry Aggression Questionnaire (BPAQ) were also used to assess impulsivity and aggression, respectively. RT-PCR was used for genotyping, a genetic effect was assessed using the dominant model. Mann-Whitney U-test, Pearson χ2-test and multiple linear regression were used for statistical analysis. RESULTS: Carriers of the minor G allele of OPRM1 gene rs1779971 had a higher level of aggression assessed by BPAQ (p=0.02). The minor C allele of OPRK1 gene rs6473797 was associated with an increase of the subjective importance of «Affect regulation¼ (B=2.23; CI 95% [0.39-4.06]; p=0.022) and «Anti-dissociation¼ (B=3.31; CI 95% [0.18-6.44]; p=0.039) motivations, whereas the minor T allele of DCC gene rs8084280, on the contrary, was associated with a decrease of the importance of «Affect regulation¼ (B=-1.74; CI 95% [-3.30 - -0.18]; p=0.032). Moreover, this effect was found after adjusting for diagnosis, sex, age, and the presence of childhood trauma. CONCLUSIONS: To our knowledge, this is the first study on the association of genetic markers with NSSI motivations. The results of this pilot study demonstrate that OPRK1 and DCC gene polymorphisms can determine differences in motivations for self-harm, however, these results require confirmation in large samples.

Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.

To explore the influence of separation from parents in childhood on suicide and self-injury behavior and psychological adjustment in adolescence. A total of 880 subjects were selected, including 197 students who were separated from their parents in childhood and 683 students who were not separated from their parents in childhood. The scores of psychological resilience, self-compassion, forgiveness and suicide and self-injury were investigated and analyzed. Logistic regression analysis was made on the relationship between suicide and self-injury behavior and psychological adjustment in adolescence. The scores of psychological resilience, self-compassion, forgiveness and suicide and self-injury were statistically significant between children who were separated from their parents and those who were not separated. The students who were not separated had better psychological adjustment abilities and a lower rate of suicide and self-injury (P<0.05). There was a positive correlation between separation from parents in childhood and suicide and self-injury behavior and psychological adjustment in adolescence (P<0.05). The separation from parents in childhood is closely related to psychological resilience, forgiveness, self-compassion, and suicide-related psychological behavior and self-injury behavior in adolescence. Suicide and self-injury behavior can be reduced by reducing separation from parents in childhood and improving self-psychological adjustment ability in adolescence. During the past years, genetics, heritability, and genes' contribution to depression disorders have been well established. Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) genes are very effective in behavioral and mood disorders. The results of this study showed the expression of these genes in different organs, especially in connection with the cerebrospinal system, so investigating the mechanism of their effect is very effective and promising, and it is hoped that they will be used in other research.

BDNF and stress/mood-related interactions on emotional disorder symptoms, executive functioning, and deliberate self-harm.

Some prior research has suggested that the brain-derived neurotrophic factor (BDNF) gene may amplify responses related to life stress (e.g., depression and anxiety) or associated with negative moods (e.g., self-harm and diminished cognitive functioning). The purpose of this study was to investigate whether stress/mood-related associations with depressive and anxiety symptoms, deliberate self-harm, and executive functioning (EF) are moderated by genotypic variations in BDNF rs10835210 (a relatively understudied BDNF polymorphism) in a nonclinical sample. As part of a larger study, European American social drinkers (N = 132; 43.9% female; M age = 26.0, SD = 7.6) were genotyped for BDNF rs10835210 and were administered self-report measures of subjective life stress, depressive and anxiety symptoms, and history of non-suicidal self-injury (NSSI) and behavioral measures of EF and deliberate self-harm. Results indicated that BDNF significantly moderated the life stress associations with depressive symptoms and NSSI, the anxious mood association with EF, and the depressed mood association with deliberate self-harm behavior. Each of these BDNF × stress/mood interactions were characterized by stress/mood associations that were stronger in individuals with the AA genotype (homozygous for the minor allele) than in individuals possessing a genotype that included the major allele (AC or CC). The main limitations of the present study were use of a cross-sectional design, modest sample size, and investigating only one BDNF polymorphism. Despite these limitations and though preliminary, current findings suggest that variations in BDNF may confer vulnerability to stress or mood, which may result in more adverse emotional, cognitive, or behavioral outcomes.

A PUS7 gene pathogenic variant causing self-injurious behavior, sleep disturbances, and developmental delay: A case report.

PUS7 gene pathogenic variants cause a deficiency in an RNA-independent pseudouridine synthase, which results in a neurodevelopmental phenotype characterized by various degrees of psychomotor delay, acquired microcephaly, aggressive behavior, and intellectual disability. Since 2018, PUS7 deficiency has been described in 15 patients with different pathogenic variants but similar clinical phenotypes. We describe the case of a male infant with a homozygous truncating pathogenic variant in the PUS7 gene (c.329_332delCTGA; p.Thr110Argfs*4) who, in addition to the previously mentioned features, displays self-injurious behavior, sleep disturbances and motor stereotypies.

Association between birth by caesarian section and anxiety, self-harm: a gene-environment interaction study using UK Biobank data.

BACKGROUND: Limited efforts have been paid to explore the underlying genetic mechanisms of birth by caesarian section (CS) affecting the risks of adult anxiety and self-harm. METHODS: Using UK Biobank cohort, the logistic regression model was first applied to evaluate the associations of adult anxiety and self-harm with birth by CS. Using birth by CS as exposure variables, genome-wide by environment interaction study (GWEIS) was then applied by PLINK2.0 to identify associated genes interacting with birth by CS for anxiety and self-harm. RESULTS: In the observational study, significant associations were observed between birth by CS and anxiety (odds ratio (OR) = 1.24; 95% confidence interval (CI), 1.12-1.38; P = 4.86 × 10- 5), and self-harm (OR = 1.12; 95% CI, 1.01-1.24; P = 2.90 × 10- 2). GWEIS revealed multiple suggestive genes interacted with birth by CS for anxiety, such as DKK2 (rs13137764, P = 1.24 × 10- 9, adjusted P = 2.68 × 10- 7) and ATXN1 (rs62389045, P = 4.38 × 10- 8, adjusted P = 3.55 × 10- 6). For self-harm, significant gene-environment interactions of birth by CS on self-harm were detected, such as ALDH1A2 (rs77828167, P = 1.62 × 10- 8; rs116899929, P = 1.92 × 10- 8) and DAB1 (rs116124269, P = 3.20 × 10- 8; rs191070006, P = 3.63 × 10- 8). CONCLUSIONS: Our results suggested that birth by CS was associated with the risk of adult anxiety and self-harm. We also discovered some genes interacted with birth by CS might influence the risk of anxiety and self-harm, which may provide novel clues for the pathogenesis of those mental disorders.

Longitudinal relation between maladaptive parenting and nonsuicidal self-injury among Chinese early adolescents: The roles of internalizing symptoms and FKBP5 gene variation.

BACKGROUND: While increasing research has effectively documented that maladaptive parenting is a significant risk factor for adolescent nonsuicidal self-injury, the process mechanism and gene-by-environment interaction in this relation among Chinese early adolescents are still poorly understood. METHODS: In this study, a multi-informant longitudinal design was applied to investigate the indirect effect of internalizing symptoms in the relation between maladaptive parenting and nonsuicidal self-injury, and to examine how FKBP5 gene variation moderates these association. A total of 1718 Chinese Han early adolescents (44.30 % girls; Mage at Wave 1 = 10.35) and their parents participated this study. RESULTS: The results showed that maladaptive parenting significantly predicts adolescent nonsuicidal self-injury after six months. Maladaptive parenting was also indirectly related to nonsuicidal self-injury via internalizing symptoms. Moreover, using a cumulative genetic score approach, the results showed that FKBP5 gene variation moderates the predictive effect of maladaptive parenting on internalizing symptoms and also moderates the indirect effect of internalizing symptoms between maladaptive parenting and nonsuicidal self-injury. These effects were more salient among adolescents with high (versus low) FKBP5 gene related cumulative genetic score linked to heightened stress reactivity. LIMITATIONS: Our study only obtained two waves of data. Three waves of data would be more suitable for examining a mediation model. CONCLUSION: This study reveals the process mechanism between maladaptive parenting and nonsuicidal self-injury and highlights the significance of gene-by-environment interaction to explain the emergence of nonsuicidal self-injury among adolescents.

Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.

OBJECTIVE: To investigate the association of postpartum depressive symptoms (PDS) and self-harm ideation with n-methyl-d-aspartate (NMDA) receptor GRIN2B and GRIN3A gene polymorphisms and other risk factors in women undergoing cesarean section. METHODS: A total of 362 parturients undergoing cesarean section under lumbar anesthesia were selected and their postpartum depression level was assessed by the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum, with an EPDS score of 9/10 as the cut-off value. Three GRIN2B SNP loci (rs1805476, rs3026174, rs4522263) and five GRIN3A SNP loci (rs1983812, rs2050639, rs2050641, rs3739722, rs10989563) were selected for genotype detection. The role of each SNP, linkage disequilibrium and haplotypes in the development of postpartum depression was analyzed. Logistic regression analysis was performed for related risk factors. RESULTS: PDS incidence was 16.85%, and self-harm ideation incidence was 13.54%. Univariate analysis showed that GRIN2B rs1805476, rs3026174 and rs4522263 gene polymorphisms were associated with PDS (p < 0.05), with GRIN2B rs4522263 gene also associated with maternal self-harm ideation. GRIN3A rs1983812, rs2050639, rest rs2050641, rs3739722 and rs10989563 alleles were not associated with PDS. Logistic regression analysis indicated that high pregnancy stress, as well as rs1805476 and rs4522263 alleles were PDS risk factors following cesarean delivery. GRIN2B (TTG p = 0.002) and GRIN3A (TGTTC p = 0.002) haplotypes were associated with the lower PDS incidence and higher PDS incidence respectively. CONCLUSION: GRIN2B rs1805476 GG genotype, rs4522263 CC genotype and high stress during pregnancy were risk factors for PDS, whilst a significantly higher incidence of self-harm ideation was evident in parturients carrying GRIN2B rs4522263 CC genotype.

School performance and genetic propensities for educational attainment and depression in the etiology of self-harm: a Danish population-based study.

BACKGROUND: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRSMDD) and for educational attainment (PRSEDU). METHOD: We conducted a follow-up study of individuals born 1987-98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers. RESULTS: Individuals in the top PRSMDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15-1.46), whereas individuals in the top PRSEDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55-0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44-1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47-15.18). Observed effects of PRSMDD and PRSEDU on self-harm risk were strongest for individuals with poor school performance. CONCLUSION: Associations between PRSMDD and self-harm risk and between PRSEDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

Molecular examination of the endogenous opioid system in rhesus macaque monkeys with self-injurious behavior.

Self-injurious behavior (SIB) can lead to serious injury and occurs in approximately 1%-4% of the adult population, with higher incidences in adolescent and institutionalized populations, as well as in children with developmental disorders such as Autism. SIB also spontaneously occurs in a low percentage of captive monkeys. Rhesus macaque (Macaca mulatta) monkeys are evolutionarily and physiologically similar to humans, share 93% genetic sequence similarity to humans, and have long been used as testing subjects for vaccine and clinical trials. Previous studies hypothesized that altered endogenous opioid expression occurs in the brains of individuals and animals that self-injure. We examined the regional mRNA expression of opioid signaling genes in sixteen rhesus macaques that exhibited SIB and eight sex- and age- matched controls. The brain regions examined are linked to reward reinforcement and stress adaptation including the hypothalamus, orbital frontal cortex, nucleus accumbens, hippocampus, caudate, and the amygdala. We found decreased µ-opioid receptor (OPRM1) in the amygdala of monkeys with SIB, and reduced prodynorphin (PDYN) in the hypothalamus. Our data suggest dysfunction in the regulation of opioid peptide precursors and calls for further investigation of the endogenous opioid system in SIB.

Parent-Adolescent Conflict, Depressive Symptoms, and Non-Suicidal Self-Injury among Chinese Adolescents: The Moderating Effect of the COMT Gene rs4680 Polymorphism.

Existing research suggests that parent-adolescent conflict is associated with increased risk for adolescent non-suicidal self-injury (NSSI). However, adolescent NSSI reactions to parent-adolescent conflicts exhibit large individual differences. This study sought to explore whether depressive symptoms mediates the relationship between parent-adolescent conflict and adolescent NSSI, and whether this mediating process is moderated by the COMT gene rs4680 polymorphism. A total of 673 adolescents (364 males, 309 females) in the age range of 12 to 15 years (Meanage = 12.81 years, SD = 0.48) completed questionnaires regarding parent-adolescent conflict, depressive symptoms, and NSSI. Genomic DNA was extracted from saliva and buccal cells from each participant. Bootstrapping techniques displayed statistically significant moderated mediation. The results showed that the positive association between parent-adolescent conflict and adolescent NSSI was in fact mediated by depressive symptoms. Moreover, this indirect link was moderated by the COMT gene rs4680 polymorphism. Specifically, the risk effect of parent-adolescent conflict on adolescent NSSI via depressive symptoms was stronger for adolescents with Val/Val genotype than for those with Met/Met or Val/Met genotype. These findings underscore the importance of examining the interaction between genes and the environment to understand how and when parent-adolescent conflict impacts adolescent NSSI.

Investigating the causal risk factors for self-harm by integrating Mendelian randomisation within twin modelling.

Previous genetically informed studies have uncovered likely causal relationships between mental health problems and self-harm but resulting causal estimates may be biased due to unmediated pleiotropy. By fitting Mendelian Randomization - Direction of Causation (MR-DoC) models that explicitly model pleiotropy, we investigated the effect of four quantitatively measured mental health problems - major depressive disorder (MDD), schizophrenia, attention-deficit hyperactivity disorder (ADHD), and insomnia, on non-suicidal self-harm (NSSH) and suicidal self-harm (SSH), separately. We used data of 12,723 twins (56.6% females) in the Twins Early Development Study. Besides substantial pleiotropy, we found effects from child-rated depressive symptoms to both NSSH (ß = 0.194, 95% CIs: 0.131, 0.257) and SSH (ß = 0.210, 95% CIs: 0.125, 0.295). Similarly, effects flowed from parent-rated depressive symptoms to NSSH (ß = 0.092, 95% CIs: 0.004, 0.181) and SSH (ß = 0.165, 95% CIs: 0.051, 0.281). We did not find evidence of aetiological difference between NSSH and SSH.

Genetics and epigenetics of self-injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations.

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.

A multi-environments-gene interaction study of anxiety, depression and self-harm in the UK Biobank cohort.

The effects of gene-by-environment (G×E) interactions on complex diseases are significant, especially the superimposed effects of multiple environmental factors. However, research on the multi-environments-gene interactions of anxiety, depression, and self-harm is still limited. This study included white individuals (N = 66,041-74,482) from the UK Biobank. We fitted all environmental factors to a single environmental score (ES), and the estimated ES was used to calculate the multiplicative interaction effects between ES and genome-wide SNPs. Heritability was stratified by minor allele frequency (MAF) and linkage disequilibrium (LD). Our research found 10 loci with significant interaction effects, such as rs114830993 (PRICKLE2, P = 2.30 × 10-8), rs151323364 (ASTN2, P = 2.71 × 10-10) and rs536631793 (SYN3, P = 4.09 × 10-8). In addition, we found that G×E heritability has a significant contribution to the depression of Patient Health Questionnaire-9 (PHQ-9) scores (h2G×E (female) = 6.1%, h2G×E (male) = 8.7%). Our research supported the important influence of multi-environments-gene interactions on anxiety, depression, and self-harm and provided clues for the prevention and etiological research of them.

A nonhuman primate model of human non-suicidal self-injury: serotonin-transporter genotype-mediated typologies.

While non-suicidal self-injury (NSSI) occurs in the general population at a surprisingly high rate, with higher rates among certain clinical  populations, its etiology is not well-understood. Consequently, the DSM-5 lists NSSI as requiring further research. This study utilizes a translational model of naturally-occurring NSSI to assess the role of early parental neglect and variation in the serotonin transporter genotype (5-HTT) in the etiology of NSSI. Subjects (N = 161) were rhesus macaques (Macaca mulatta) reared in one of three conditions (mother-reared (MR), peer-reared (PR), or surrogate peer-reared (SPR)), and classified as NSSI (n = 18) or non-NSSI (n = 143). Subjects were genotyped for 5-HTT and their behaviors were recorded during an ecologically-meaningful, stress-evoking, intruder paradigm. Two weeks prior to testing, blood samples were obtained and assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. NSSI subjects were more likely to be SPR, paralleling human studies showing that individuals that exhibit NSSI tend to have experienced abuse or neglect early in life. Results also indicated that variation in the 5-HTT genotype differentiated the NSSI subjects. NSSI subjects that were homozygous for the L allele exhibited high plasma ACTH and high rates of stress-induced stereotypies; whereas NSSI subjects with the s allele exhibited impulsive behaviors, including frequently approaching the potentially dangerous intruder, high rates of aggressive vocal threats, and more activity. These results suggest that there may be different 5-HTT genotype-mediated NSSI typologies and that both early experiences and variation in the 5-HTT genotype may be important factors in understanding the etiology of NSSI.

N-Acetylcysteine provides limited efficacy as treatment option for skin picking in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome region 15q11-13. In addition to typical characteristics such as hyperphagia, PWS is evidenced by a certain behavioral phenotype. Common indicators are repetitive behaviors, temper tantrums, and self-injurious behaviors such as skin- and/or rectal picking. N-Acetylcysteine (NAC) was previously described as a promising therapeutic option for skin picking in PWS. In this case series, we retrospectively investigated the effect of pharmacotherapy with NAC in 14 individuals with PWS suffering from skin- and/or rectal picking. Treatment success was determined using the Clinical Global Impression-Improvement scale (CGI-I). The Clinical Global Impression-Efficacy index (CGI-EI) was used to put treatment success and side effects into perspective. Six of fourteen patients, all of which were female, showed improvement in symptoms (dosage 1800-2400 mg/day), whereas six patients did not show any change during treatment. Moreover, two male patients treated for solitary rectal picking showed new onset of skin picking. Across all cases, a CGI-I of 3 (corresponding to minimal improvement) was seen after 3 months of treatment, with a CGI-EI of 1.6 (corresponding to moderate efficacy). NAC remains a reasonable therapeutic option in certain cases of skin picking in PWS but provides only limited efficacy compared to previous studies on the topic. There was a higher rate of adverse drug reactions than previously reported. The results particularly suggest caution in future treatment in individuals with solitary rectal picking and reduced efficacy when coadministered with neuroleptics.

Relationship between SIRT1 gene and adolescent depressive disorder with nonsuicidal self-injury behavior: Based on gene methylation and mRNA expression.

OBJECTIVE: The incidence of non-suicidal self-injury (NSSI) behavior in adolescents is increasing year by year. Patients with a history of both depression and NSSI behavior tend to be at greater risk for suicide. At present, the mechanism of adolescent depressive disorder with NSSI behavior is not clear and still in research and exploration. The expression of the Silent Information Regulator 2 Related Enzyme 1 (SIRT1) gene is closely related to the level of serotonin in molecular mechanisms, and may be closely related to the occurrence and development of depressive disorder. This study aimed to explore the relationship between the SIRT1 gene and NSSI behaviors in adolescents with depressive disorder. METHODS: A total of 15 adolescent depressed patients with NSSI behavior and 15 healthy controls were enrolled in the study. Bisulfite Sequencing PCR (BSP) was used to test the methylation level of SIRT1 gene promoter region of the participants. The real-time fluorescent quantitative PCR was conducted to measure the mRNA expression level of SIRT1 gene. RESULTS: Our study found that the methylation level of SIRT1 gene promoter region at cytosine-guanine dinucleotide 5 (CpG5) site in depression group was higher than that of control group. Compared with that of control group, the plasma concentration of Sirt1 protein significantly decreased in depression group. CONCLUSION: Our study investigated the methylation level and the mRNA expression of SIRT1 gene in adolescent depressive patients with NSSI behavior. The study points towards finding an in vivo molecular marker for those adolescent patients.

Epigenetic marks in suicide: a review.

Suicide is a complex phenomenon and a global public health problem that involves several biological factors that could contribute to the pathophysiology of suicide. There is evidence that epigenetic factors influence some psychiatric disorders, suggesting a predisposition to suicide or suicidal behavior. Here, we review studies of molecular mechanisms of suicide in an epigenetic perspective in the postmortem brain of suicide completers and peripheral blood cells of suicide attempters. Besides, we include studies of gene-specific DNA methylation, epigenome-wide association, histone modification, and interfering RNAs as epigenetic factors. This review provides an overview of the epigenetic mechanisms described in different biological systems related to suicide, contributing to an understanding of the genetic regulation in suicide. We conclude that epigenetic marks are potential biomarkers in suicide, and they could become attractive therapeutic targets due to their reversibility and importance in regulating gene expression.

On the Genetic and Environmental Relationship Between Suicide Attempt and Death by Suicide.

OBJECTIVE: The authors examined the extent to which the genetic and environmental etiology of suicide attempt and suicide death is shared or unique. METHODS: The authors used Swedish national registry data for a large cohort of twins, full siblings, and half siblings (N=1,314,990) born between 1960 and 1990 and followed through 2015. They conducted twin-family modeling of suicide attempt and suicide death to estimate heritability for each outcome, along with genetic and environmental correlations between them. They further assessed the relationship between suicide attempt by young people compared with adults. RESULTS: In bivariate models, suicide attempt and death were moderately heritable among both women (attempt: additive genetic variance component [A]=0.52, 95% CI=0.44, 0.56; death: A=0.45, 95% CI=0.39, 0.59) and men (attempt: A=0.41, 95% CI=0.38, 0.49; death: A=0.44, 95% CI=0.43, 0.44). The outcomes were substantially, but incompletely, genetically correlated (women: rA=0.67, 95% CI=0.55, 0.67; men: rA=0.74, 95% CI=0.63, 0.87). Environmental correlations were weaker (women: rE=0.36, 95% CI=0.29, 0.45; men: rE=0.21, 95% CI=0.19, 0.27). Heritability of suicide attempt was stronger among people ages 10-24 (A=0.55-0.62) than among those age 25 and older (A=0.36-0.38), and the genetic correlation between attempt during youth and during adulthood was stronger for women (rA=0.79, 95% CI=0.72, 0.79) than for men (rA=0.39, 95% CI=0.26, 0.47). CONCLUSIONS: The genetic and environmental etiologies of suicide attempt and death are partially overlapping, exhibit modest sex differences, and shift across the life course. These differences must be considered when developing prevention efforts and risk prediction algorithms. Where feasible, suicide attempt and death should be considered separately rather than collapsed, including in the context of gene identification efforts.

The Effects of Childhood Maltreatment on Non-Suicidal Self-Injury in Male Adolescents: The Moderating Roles of the Monoamine Oxidase A (MAOA) Gene and the Catechol-O-Methyltransferase (COMT) Gene.

(1) Background: Numerous studies suggest strong associations between childhood maltreatment and nonsuicidal self-injury (NSSI); this is also true for the roles of dopaminergic genes in the etiology of some psychopathologies related to NSSI. Investigating the interactions of environments and genes is important in order to better understand the etiology of NSSI. (2) Methods: Within a sample of 269 Chinese male adolescents (Mage = 14.72, SD = 0.92), childhood maltreatment and NSSI were evaluated, and saliva samples were collected for MAOA T941G and COMT Val158Met polymorphism analyses. (3) Results: The results revealed no primary effects attributable to MAOA T941G and COMT Val158Met polymorphism on NSSI. However, there was a significant three-way interaction between MAOA, COMT, and child abuse (ß = -0.34, p < 0.01) in adolescent NSSI. Except for carriers of the T allele of MAOA and the Met allele of COMT, all studied male adolescents displayed higher NSSI scores when exposed to a higher level of child abuse. A similar three-way interaction was not observed in the case of child neglect. (4) Conclusions: The results indicate that the MAOA gene and COMT gene play moderating roles in the association between child abuse and NSSI of male adolescents and suggest the polygenic underpinnings of NSSI.