A community's response to suicide through public art: stakeholder perspectives from the Finding the Light Within project.

Suicide is a preventable public health problem and a leading cause of death in the United States. Despite recognized need for community-based strategies for suicide prevention, most suicide prevention programs focus on individual-level change. This article presents seven first person accounts of Finding the Light Within, a community mobilization initiative to reduce the stigma associated with suicide through public arts participation that took place in Philadelphia, Pennsylvania from 2011 through 2012. The stigma associated with suicide is a major challenge to suicide prevention, erecting social barriers to effective prevention and treatment and enhancing risk factors for people struggling with suicidal ideation and recovery after losing a loved one to suicide. This project engaged a large and diverse audience and built a new community around suicide prevention through participatory public art, including community design and production of a large public mural about suicide, storytelling and art workshops, and a storytelling website. We present this project as a model for how arts participation can address suicide on multiple fronts-from raising awareness and reducing stigma, to promoting community recovery, to providing healing for people and communities in need.

Culturally responsive assessment of suicidal thoughts and behaviors in youth of color.

The significance of youth suicide as a public health concern is underscored by the fact that it is the second-leading cause of death for youth globally. While suicide rates for White groups have declined, there has been a precipitous rise in suicide deaths and suicide-related phenomena in Black youth; rates remain high among Native American/Indigenous youth. Despite these alarming trends, there are very few culturally tailored suicide risk assessment measures or procedures for youth from communities of color. This article attempts to address this gap in the literature by examining the cultural relevancy of currently widely used suicide risk assessment instruments, research on suicide risk factors, and approaches to risk assessment for youth from communities of color. It also notes that researchers and clinicians should consider other, nontraditional but important factors in suicide risk assessment, including stigma, acculturation, and racial socialization, as well as environmental factors like health care infrastructure and exposure to racism and community violence. The article concludes with recommendations for factors that should be considered in suicide risk assessment for youth from communities of color. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Genetic resistance to diet-induced obesity in chromosome substitution strains of mice.

Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-Chr(A/J)/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-Chr(A/J)/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J x A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits.

Reciprocal congenic lines of mice capture the aliq1 effect on acute lung injury survival time.

Acute lung injury (ALI) is a devastating condition resulting from diverse causes. Genetic studies of human populations indicate that ALI is a complex disease with substantial phenotypic variance, incomplete penetrance, and gene-environment interactions. To identify genes controlling ALI mortality, we previously investigated mean survival time (MST) differences between sensitive A/J (A) and resistant C57BL/6J (B) mice in ozone using quantitative trait locus (QTL) analysis. MST was significantly linked to QTLs (Aliq1-3) on chromosomes 11, 13, and 17, respectively. Additional QTL analyses of separate and combined backcross and F(2) populations supported linkage to Aliq1 and Aliq2, and established significance for previously suggestive QTLs on chromosomes 7 and 12 (named Aliq5 and Aliq6, respectively). Decreased MSTs of corresponding chromosome substitution strains (CSSs) verified the contribution of most QTL-containing chromosomes to ALI survival. Multilocus models demonstrated that three QTLs could explain the MST difference between progenitor strains, agreeing with calculated estimates for number of genes involved. Based on results of QTL genotype analysis, a double CSS (B.A-6,11) was generated that contained Aliq1 and Aliq4 chromosomes. Surprisingly, MST and pulmonary edema after exposure of B.A-6,11 mice were comparable to B mice, revealing an unpredicted loss of sensitivity compared with separate CSSs. Reciprocal congenic lines for Aliq1 captured the corresponding phenotype in both background strains and further refined the QTL interval. Together, these findings support most of the previously identified QTLs linked to ALI survival and established lines of mice to further resolve Aliq1.

Screening for anxiety and depression in community mental health: the beck anxiety and depression inventories.

Accurate diagnosis is key to providing quality services in community mental health. This research examined the ability of the Beck Anxiety and Depression Inventories to identify anxiety and depression in community settings. The diagnostic accuracy of these instruments was compared with the Structured Clinical Interview for DSM-IV in a sample of 288 distressed women seeking treatment for their children. Operating characteristic curves indicated the Beck Anxiety and Depression Inventories hold utility as screens for panic and major depressive disorder, respectively. Deploying these instruments as initial screens in a tiered diagnostic system may improve diagnostic accuracy in community settings.

Sleep-related epilepsy in the A/J mouse.

RATIONALE: Evident seizures during sleep are common in clinical practice but are uncommonly considered in animal models of epilepsy. A previous observation of spontaneous spike-and-wave activity during sleep in several A/J mice (A/J JAX) from Jackson Laboratory (Bar Harbor, ME) prompted this description of the inheritance of epileptic activity. METHODS: Mice from A/J, C57BI/6J (B6), and chromosomal substitutions strains were instrumented to record EEG and EMG activity over time without and with anti-epileptic drugs. Intercrosses were performed using linkage analysis to localize sub-chromosomal regions. RESULTS: Spike-discharge patterns (n = 12 mice) were of average duration of 1.9 seconds at a rate per hour of 17, with an intrinsic frequency of 6.41 Hz and an amplitude of 634.8 microV. Clonic movements were observed in < 10% of the episodes. Episodes were expressed (> 75%) either in slow-wave sleep or in transitions to and from slow-wave sleep. Events were rare in paradoxical sleep. Compared with vehicle, intraperitoneal administration of ethosuximide (150 mg/kg) or diazepam (5 mg/kg) inhibited or eliminated seizure activity, respectively. In contrast, spontaneous spike-and-wave activity was not observed in A/J mice from Harlan National Laboratories (Indianapolis, Ind) or in B6 mice from Jackson Laboratory. In an intercross between A/J JAX and B6 mice, the trait was not present in the first generation. The trait was observed in 2 chromosome-substitution strains, B6.A4 and B6.A7. In the intercross second generation of these chromosome-substitution strains (n = 113), significant linkage was observed to loci on chromosome 4. CONCLUSIONS: This is a sleep-related epilepsy phenotype that exhibits an oligogenic pattern of allelic inheritance.

Mapping quantitative trait loci for anxiety in chromosome substitution strains of mice.

Anxious behavior in the mouse is a complex quantitative phenotype that varies widely among inbred mouse strains. We examined a panel of chromosome substitution strains bearing individual A/J chromosomes in an otherwise C57BL/6J background in open-field and light-dark transition tests. Our results confirmed previous reports of quantitative trait loci (QTL) on chromosomes 1, 4, and 15 and identified novel loci on chromosomes 6 and 17. The studies were replicated in two separate laboratories. Systematic differences in the overall activity level were found between the two facilities, but the presence of the QTL was confirmed in both laboratories. We also identified specific effects on open-field defecation and center avoidance and distinguished them from overall open-field activity.

Two quantitative trait loci for prepulse inhibition of startle identified on mouse chromosome 16 using chromosome substitution strains.

Prepulse inhibition (PPI) of acoustic startle is a genetically complex quantitative phenotype of considerable medical interest due to its impairment in psychiatric disorders such as schizophrenia. To identify quantitative trait loci (QTL) involved in mouse PPI, we studied mouse chromosome substitution strains (CSS) that each carry a homologous chromosome pair from the A/J inbred strain on a host C57BL/6J inbred strain background. We determined that the chromosome 16 substitution strain has elevated PPI compared to C57BL/6J (P = 1.6 x 10(-11)), indicating that chromosome 16 carries one or more PPI genes. QTL mapping using 87 F(2) intercross progeny identified two significant chromosome 16 loci with LODs of 3.9 and 4.7 (significance threshold LOD is 2.3). The QTL were each highly significant independently and do not appear to interact. Sequence variation between B6 and A/J was used to identify strong candidate genes in the QTL regions, some of which have known neuronal functions. In conclusion, we used mouse CSS to rapidly and efficiently identify two significant QTL for PPI on mouse chromosome 16. The regions contain a limited number of strong biological candidate genes that are potential risk genes for psychiatric disorders in which patients have PPI impairments.

Genetic background determines response to hemostasis and thrombosis.

BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5A/J, B6-Chr11A/J, and B6-Chr17A/J, were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5A/J and B6-Chr17A/J, were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. CONCLUSION: These results indicate that susceptibility to arterial thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk.

Interacting genetic loci cause airway hyperresponsiveness.

Airway hyperresponsiveness (AHR) is a key physiological component of asthma, and the genetic basis of this complex trait has remained elusive. We created recombinant congenic mice with increased naive AHR by serially backcrossing A/J mice (which have elevated naive AHR) with C57BL/6J mice and selecting for mice with an elevated naive AHR phenotype. The seventh backcross-generation hyperresponsive mice retained A/J loci in three regions. Quantitative trait linkage (QTL) analysis of 123 unselected N8 progeny demonstrated that the AHR phenotype was not associated with any single locus but was significantly associated with an interaction of loci on chromosomes 2 and 6. These findings were confirmed in an independent analysis of chromosome substitution strain mice. The identification of genomic regions containing loci causally associated with AHR and the demonstration that this trait requires their interaction have important implications for the dissection of the genetic etiology of asthma in humans.

A complex interaction of imprinted and maternal-effect genes modifies sex determination in Odd Sex (Ods) mice.

The transgenic insertional mouse mutation Odd Sex (Ods) represents a model for the long-range regulation of Sox9. The mutation causes complete female-to-male sex reversal by inducing a male-specific expression pattern of Sox9 in XX Ods/+ embryonic gonads. We previously described an A/J strain-specific suppressor of Ods termed Odsm1(A). Here we show that phenotypic sex depends on a complex interaction between the suppressor and the transgene. Suppression can be achieved only if the transgene is transmitted paternally. In addition, the suppressor itself exhibits a maternal effect, suggesting that it may act on chromatin in the early embryo.

Chromosomes 6 and 13 harbor genes that regulate pubertal timing in mouse chromosome substitution strains.

Variation in the onset of puberty among inbred strains of mice suggests that quantitative trait loci (QTLs) affect neurological and hormonal aspects of sexual maturation. Taking a novel approach toward identifying factors that regulate the hypothalamic-pituitary-gonadal (HPG) axis, we evaluated pubertal timing [as assessed by vaginal opening (VO)] in two inbred strains of mice, A/J and C57BL/6J (B6), and in a panel of chromosome substitution strains (CSSs) generated from A/J and B6 mice. In each CSS, a single chromosome from A/J has been substituted in a homozygous fashion for the corresponding chromosome in B6, partitioning the A/J genome into 22 strains with a common host (B6) background. VO occurred significantly earlier in A/J compared with B6 mice. Although the majority of the CSSs assessed had a timing of VO that was similar to the progenitor B6 strain, CSSs for chromosomes 6 and 13 each displayed significantly earlier time of VO than B6 mice. F1 (B6 x CSS) mice for chromosomes 6 and 13 displayed phenotypes that were intermediate between the CSS and B6 strains, suggesting that the trait was inherited in a codominant manner. These findings demonstrate that chromosomes 6 and 13 harbor QTLs that control the timing of VO. Identification of the responsible genes may reveal factors that regulate the maturation of the HPG axis and determine the timing of puberty.

Emotional support and adult depression in survivors of childhood sexual abuse.

The goals of this study were to evaluate the effects of emotional support from friends and parents at two time points (adolescence and adulthood) on adult depression in a nationally representative sample of survivors of childhood sexual abuse (CSA), and examine whether the associations were moderated by the identity of the perpetrator (parent/caregiver vs. not). Data were taken from Waves I and IV of the National Longitudinal Study of Adolescent Health (Add Health). The study sample included 1,238 Add Health participants with a history of CSA and an equivalently sized comparison group of individuals with no history of CSA. Parental support was measured using four items from each wave that assessed the warmth of participants' relationships with their parents and their satisfaction with those relationships. Friend support in adolescence was measured using participants' perceptions of how much their friends cared about them and in adulthood using participants' self-reported number of close friends. Depression was measured using a 10-item subscale of the CES-D. Logistic regressions showed that support from friends and parents in adulthood were significantly associated with lower odds of adult depression in CSA survivors who reported non-parent/caregiver abuse. Among survivors of parent/caregiver abuse, emotional support was not significantly associated with adult depression regardless of when or by whom it was provided. In conclusion, emotional support in adulthood from friends and parents is associated with reduced odds of adult depression in CSA survivors, but only in cases where the abuse was perpetrated by someone other than a parent or caregiver.

Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents.

Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored.

A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury.

Lumiracoxib is a selective cyclooxygenase-2 inhibitor developed for the symptomatic treatment of osteoarthritis and acute pain. Concerns over hepatotoxicity have contributed to the withdrawal or non-approval of lumiracoxib in most major drug markets worldwide. We performed a case-control genome-wide association study on 41 lumiracoxib-treated patients with liver injury (cases) and 176 matched lumiracoxib-treated patients without liver injury (controls). Several SNPs from the MHC class II region showed strong evidence of association (the top SNP was rs9270986 with P = 2.8 x 10(-10)). These findings were replicated in an independent set of 98 lumiracoxib-treated cases and 405 matched lumiracoxib-treated controls (top SNP rs3129900, P = 4.4 x 10(-12)). Fine mapping identified a strong association to a common HLA haplotype (HLA-DRB1*1501-HLA-DQB1*0602-HLA-DRB5*0101-HLA-DQA1*0102, most significant allele P = 6.8 x 10(-25), allelic odds ratio = 5.0, 95% CI 3.6-7.0). These results offer the potential to improve the safety profile of lumiracoxib by identifying individuals at elevated risk for liver injury and excluding them from lumiracoxib treatment.

Candidate gene association analysis.

Candidate gene association study is the most common method for associating human genetic variations with the phenotypes they produce, due to the relative simplicity of acquiring patient samples and genotype data. The study design begins with identifying appropriate DNA samples and an appropriate phenotype for analysis. The candidate genes and polymorphisms must then be chosen. After genotyping the candidate genes in the DNA samples, the results are checked to ensure appropriate quality and association analysis is performed. The raw results are interpreted and placed into context and follow-up analysis is carried out to validate and refine the findings. A wide range of software packages are available for both the association analysis and other steps in the study. This chapter describes the use of PLINK as the analysis tool in an example, as that suite has emerged as the most popular option for genetic association testing.

Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients.

The Assessment of Lescol in Renal Transplantation clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular (CV) disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1,404 patients, which allowed association testing of baseline measures and longitudinal analysis of the 707 fluvastatin-treated and 697 placebo-treated individuals. A candidate gene approach, examining 42 polymorphisms in 18 genes, was used to test for association between selected polymorphisms and major adverse cardiac events, graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol. Reported associations between cholesteryl ester transfer protein (CETP) and baseline HDL cholesterol were replicated, with four previously implicated single nucleotide polymorphisms significantly associated in males and one in females; tests of reported associations between CETP and CV disease yielded varying results. We found no evidence for genetic factors affecting fluvastatin response. Polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) previously reported to affect the efficacy of pravastatin did not show a similar effect on the reduction of LDL cholesterol by fluvastatin.

Genetic dissection of complex traits with chromosome substitution strains of mice.

Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.