Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide notes and psychiatric history

Objective A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation—the other two major, but overtly violent methods. Methods This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011–2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. Results A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43–49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11–44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11–2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10–1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06–66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19–3.18) and depression (OR, 1.48; 95% CI, 1.17–1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. Conclusions Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study

Background Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as ‘accidents,’ and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. Methods Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention’s (CDC’s) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC’s Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. Results 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to$1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%—from $318.6 billion to$502.7 billion. National per capita costs of SIM doubled from $1,638 to$3,413 over the observation period; costs of the suicide component rose from $1,137 to$1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and − 1%, respectively. Conclusion The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs—fiscal, social, and personal—incurred by deaths due to self-injurious behaviors

Fatal self-injury in the United States, 1999–2018: Unmasking a national mental health crisis

Background Suicides by any method, plus ‘nonsuicide’ fatalities from drug self-intoxication (estimated from selected forensically undetermined and ‘accidental’ deaths), together represent self-injury mortality (SIM)—fatalities due to mental disorders or distress. SIM is especially important to examine given frequent undercounting of suicides amongst drug overdose deaths. We report suicide and SIM trends in the United States of America (US) during 1999–2018, portray interstate rate trends, and examine spatiotemporal (spacetime) diffusion or spread of the drug self-intoxication component of SIM, with attention to potential for differential suicide misclassification. Methods For this state-based, cross-sectional, panel time series, we used de-identified manner and underlying cause-of-death data for the 50 states and District of Columbia (DC) from CDC's Wide-ranging Online Data for Epidemiologic Research. Procedures comprised joinpoint regression to describe national trends; Spearman's rank-order correlation coefficient to assess interstate SIM and suicide rate congruence; and spacetime hierarchical modelling of the ‘nonsuicide’ SIM component. Findings The national annual average percentage change over the observation period in the SIM rate was 4.3% (95% CI: 3.3%, 5.4%; p6.0% increase (p<0.05). Interpretation Depiction of rising SIM trends across states and major regions unmasks a burgeoning national mental health crisis. Geographic variation is plausibly a partial product of local heterogeneity in toxic drug availability and the quality of medicolegal death investigations. Like COVID-19, the nation will only be able to prevent SIM by responding with collective, comprehensive, systemic approaches. Injury surveillance and prevention, mental health, and societal well-being are poorly served by the continuing segregation of substance use disorders from other mental disorders in clinical medicine and public health practice

A comparison of in vitro properties of resting SOD1 transgenic microglia reveals evidence of reduced neuroprotective function

<p>Abstract</p> <p>Background</p> <p>Overexpression of mutant copper/zinc superoxide dismutase (<it>SOD1</it>) in rodents has provided useful models for studying the pathogenesis of amyotrophic lateral sclerosis (ALS). Microglia have been shown to contribute to ALS disease progression in these models, although the mechanism of this contribution remains to be elucidated. Here, we present the first evidence of the effects of overexpression of mutant (TG G93A) and wild type (TG WT) human <it>SOD1 </it>transgenes on a set of functional properties of microglia relevant to ALS progression, including expression of integrin β-1, spreading and migration, phagocytosis of apoptotic neuronal cell debris, and intracellular calcium changes in response to an inflammatory stimulus.</p> <p>Results</p> <p>TG SOD1 G93A but not TG SOD1 WT microglia had lower expression levels of the cell adhesion molecule subunit integrin β-1 than their NTG control cells [NTG (G93A) and NTG (WT), respectively, 92.8 ± 2.8% on TG G93A, 92.0 ± 6.6% on TG WT, 100.0 ± 1.6% on NTG (G93A), and 100.0 ± 2.7% on NTG (WT) cells], resulting in decreased spreading ability, with no effect on ability to migrate. Both TG G93A and TG WT microglia had reduced capacity to phagocytose apoptotic neuronal cell debris (13.0 ± 1.3% for TG G93A, 16.5 ± 1.9% for TG WT, 28.6 ± 1.8% for NTG (G93A), and 26.9 ± 2.8% for NTG (WT) cells). Extracellular stimulation of microglia with ATP resulted in smaller increase in intracellular free calcium in TG G93A and TG WT microglia relative to NTG controls (0.28 ± 0.02 μM for TG G93A, 0.24 ± 0.03 μM for TG WT, 0.39 ± 0.03 μM for NTG (G93A), and 0.37 ± 0.05 μM for NTG (WT) microglia).</p> <p>Conclusions</p> <p>These findings indicate that, under resting conditions, microglia from mutant <it>SOD1 </it>transgenic mice have a reduced capacity to elicit physiological responses following tissue disturbances and that higher levels of stimulatory signals, and/or prolonged stimulation may be necessary to initiate these responses. Overall, resting mutant <it>SOD1</it>-overexpressing microglia may have reduced capacity to function as sensors of disturbed tissue/cellular homeostasis in the CNS and thus have reduced neuroprotective function.</p

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed &gt;50 loci at which common variants with minor allele frequency &gt;5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value &lt; 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR &lt; 0.05) genes and 127 significantly (FDR &lt; 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels