The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins:a retrospective cohort study

Background: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. Methods: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992–93 (sample 1), 1996–2000 (sample 2), and 2005–09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. Findings: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11–3·53) and suicidal ideation (2·47, 1·19–5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation. Interpretation: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors

Genetic aetiology of self-harm ideation and behaviour

Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h) estimates were ~10%, and both traits were highly genetically correlated (LDSC r > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant

The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders

Introduction: Forms of childhood trauma tend to co-occur and are associated with increased risk for psychiatric and substance use disorders. Commonly used binary measures of trauma exposure have substantial limitations. Methods: We performed multigroup confirmatory factor analysis (CFA), separately by sex, using data from the Childhood Trauma (CT) Study's sample of twins and siblings (N = 2594) to derive three first-order factors (childhood physical abuse, childhood sexual abuse, and parental partner abuse) and, as hypothesized, one higher order, childhood trauma factor (CTF) representing a measure of their common variance. Results: CFA produced a good-fitting model in the CT Study; we replicated the model in the Comorbidity and Trauma (CAT) Study's sample (N = 1981) of opioid-dependent cases and controls. In both samples, first-order factors are moderately correlated (indicating they measure largely unique, but related constructs) and their loadings on the CTF suggest it provides a reasonable measure of their common variance. We examined the association of CTF score with risk for psychiatric and substance use disorders in these samples and the OZ-ALC GWAS sample (N = 1538) in which CT Study factor loadings were applied. We found that CTF scores are strongly associated with liability for psychiatric and substance use disorders in all three samples; estimates of risk are extremely consistent across samples. Conclusions: The CTF is a continuous, robust measure that captures the common variance across forms of childhood trauma and provides a means to estimate shared liability while avoiding multicollinearity. Confirmatory factor analysis was used to derive a higher order, childhood trauma factor representing a measure of the common variance across three forms of trauma: childhood physical abuse, childhood sexual abuse, and parental partner abuse. We replicated the model in a second sample. We then examined the association of childhood trauma score with risk for psychiatric and substance use disorders in these samples and a third sample in which the primary sample's factor loadings were applied finding factor scores to be strongly and consistently associated with liability for psychiatric and substance use disorders in all three samples

Suggestive linkage on chromosome 2, 8, and 17 for lifetime major depression

It is well established that major depressive disorder (MDD) is partly heritable. We present a genome-wide linkage study aiming to find regions on the genome that influence the vulnerability for MDD. Our sample consists of 110 Australian and 23 Dutch pedigrees with two or more siblings affected with MDD (total N = 278). Linkage analysis was carried out in MERLIN. Three regions showed suggestive linkage signals. The highest LOD-score of 2.1 was found on chromosome 17 at 52.6 cM along with LOD scores of 1.9 and 1.7 on chromosome 8 at 2.7 cM and chromosome 2 at 90.6 cM, respectively. The result on chromosome 8 seems most promising as two previous studies also found linkage in this region, once suggestive and once significant. The linkage peak on chromosome 17 harbors the serotonin transporter gene. In the Australian and Dutch sample, the serotonin transporter length polymorphism did not show evidence for association, thus other genes in this region or other polymorphisms in the serotonin transporter gene might be associated with MDD. Further replication is needed to establish the relevance of our linkage finding on chromosome 2

Early Onset Alcohol Use and Self-Harm: A Discordant Twin Analysis

Background Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Whereas early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. The current study aimed to further examine the link between EAU and both non-suicidal self-injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence. Methods Using data from 6,082 Australian same-sex twin pairs (1,732 MZ and 1,309 DZ), ages 23-40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self-harm within twin pairs discordant for EAU. Results Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly four-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across monozygotic (MZ) and dizygotic (DZ) twins. EAU also was associated with elevated odds of NSSI (OR=7.62), although this was only the case for DZ twins in discordant pairs. Conclusions The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI.Psycholog