The Effects of Multiple Interpersonal Traumas on Psychological Maladjustment of Sexually Abused Children in Korea

The purpose of the present study was to explore the effects of multiple interpersonal traumas on psychiatric diagnosis and behavior problems of sexually abused children in Korea. With 495 children (ages 4–13 years) referred to a public counseling center for sexual abuse in Korea, we found significant differences in the rate of psychiatric diagnoses (r = .23) and severity of behavioral problems (internalizing d = 0.49, externalizing d = 0.40, total d = 0.52) between children who were victims of sexual abuse only (n = 362) and youth who were victims of interpersonal trauma experiences in addition to sexual abuse (n = 133). The effects of multiple interpersonal trauma experiences on single versus multiple diagnoses remained significant in the logistic regression analysis where demographic variables, family environmental factors, sexual abuse characteristics, and postincident factors were considered together, odds ratio (OR) = 0.44, 95% confidence interval (CI) = [0.25, 0.77], p < .01. Similarly, multiple regression analyses revealed a significant effect of multiple interpersonal trauma experiences on severity of behavioral problems above and beyond all aforementioned variables (internalizing β =.12, p = .019, externalizing β = .11, p = .036, total β = .14, p =.008). The results suggested that children with multiple interpersonal traumas are clearly at a greater risk for negative consequences following sexual abuse.     

Associations between the Trauma Memory Quality Questionnaire and posttraumatic stress symptoms in youth: A systematic review and meta-analysis

Cognitive models of posttraumatic stress disorder (PTSD) propose that trauma memory characteristics are implicated in the etiology of the disorder. Empirical support for cognitive models in youth is necessary to ensure psychological interventions are based on appropriate theory. This meta-analysis was conducted to quantitatively investigate the strength of the associations between self-reported trauma memory characteristics (e.g., sensory and temporal features), measured using the Trauma Memory Quality Questionnaire (TMQQ), and posttraumatic stress symptoms (PTSS) in children and adolescents. PsycINFO, MEDLINE, CINAHL, PTSDPubs, and ProQuest Dissertations and Theses Global were searched for relevant literature. In total, 11 studies (N = 1,270 participants) met the inclusion criteria for the random-effects meta-analysis. A large effect size was observed for the association between trauma memory characteristics and PTSS, r = .51, 95% CI [.44, .58], and was maintained in subgroup analyses of the prospective association between trauma memory characteristics and later PTSS (k = 5, n = 6 28), r = .51, 95% CI [.42, .59]. A slightly larger effect size was observed in subgroup analyses of the cross-sectional association between trauma memory characteristics and concurrent PTSS (k = 11, N = 1,270), r = .62, 95% CI [.53, .70]. Sensitivity analyses on study quality, TMQQ alteration, chronic trauma exposure, geographical location, and PTSS measure supported the robustness of these results. These findings provide empirical support for the role of trauma memory characteristics in PTSS, congruent with cognitive models, suggesting this theoretical framework is appropriate for youth populations. Limitations and recommendations for future research are discussed.     

Gender Differences in Threat Biases: Trauma Type Matters in Posttraumatic Stress Disorder

Women are diagnosed with posttraumatic stress disorder (PTSD) at twice the rate of men. This gender difference may be related to differences in PTSD experiences (e.g., more hypervigilance in women) or types of trauma experienced (e.g., interpersonal trauma). We examined whether attentional threat biases were associated with gender, PTSD diagnosis, and/or trauma type. Participants were 70 civilians and veterans (38 women, 32 men; 41 with PTSD, 29 without PTSD) assessed with the Clinician Administered PTSD Scale for DSM‐IV who completed a facial dot‐probe attention bias task and self‐report measures of psychiatric symptoms and trauma history. Factorial ANOVA and regression models examined associations between gender, PTSD diagnosis, index trauma type, lifetime traumatic experiences, and attentional threat biases. Results revealed that compared to women without PTSD and men both with and without PTSD, women with PTSD demonstrated attentional biases toward threatening facial expressions, d = 1.19, particularly fearful expressions, d = 0.74. Psychiatric symptoms or early/lifetime trauma did not account for these attentional biases. Biases were related to interpersonal assault index traumas, η_p² = .13, especially sexual assault, d = 1.19. Trauma type may be an important factor in the development of attentional threat biases, which theoretically interfere with trauma recovery. Women may be more likely to demonstrate attentional threat biases due to higher likelihood of interpersonal trauma victimization rather than due to gender‐specific psychobiological pathways. Future research is necessary to clarify if sexual assault alone or in combination with gender puts individuals at higher risk of developing PTSD.     

Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN)

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65–77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020–March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.     

Childhood Trauma and the Inability to Access Hospital Care Among People who Inject Drugs

Childhood traumatic experiences can disrupt attachment, influence personality development, and precipitate chronic disease. Although the repercussions of these experiences may also pose a barrier to healthcare, few studies have examined the association between childhood trauma and access to healthcare. Therefore, we sought to investigate whether a history of childhood trauma is associated with self‐reported inability to access hospital care among persons who inject drugs (PWID). Data were derived from two prospective cohorts of PWID in Vancouver, Canada. We used multivariable generalized estimating equations to examine associations between five types of childhood trauma and self‐reported inability to access hospital care, both overall and specifically due to perceived mistreatment by hospital staff. In total, 300 participants (18.3%) reported having tried but being unable to access hospital care in the previous 6 months at some point during the study period; the primary reason was perceived mistreatment by hospital staff (32.1%). In multivariable analyses, childhood emotional abuse was independently associated with self‐reported inability to access hospital care, adjusted odds ratio (AOR) = 1.51, 95% CI [1.03, 2.20]. Childhood physical neglect was also independently associated with inability to access care due to perceived mistreatment by hospital staff, AOR = 1.80, 95% CI [1.11, 2.93]. This suggests potentially damaging consequences of early trauma in adult PWID populations. Further, this study emphasizes the need for trauma‐informed models of care as well as the need to improve therapeutic alliances with survivors of childhood trauma in the PWID population.     

SIRT1/HERC4 Locus Associated With Bisphosphonate‐Induced Osteonecrosis of the Jaw: An Exome‐Wide Association Analysis

Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole‐exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta‐analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single‐nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case‐control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome‐wide association meta‐analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01–0.46; p = 3.83 × 10^?5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10–0.88), 0.26 (0.12–0.55), and 0.26 (0.12–0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP‐induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

Association of Bone Morphogenetic Proteins With Otosclerosis

We studied the role of polymorphisms in 13 candidate genes on the risk of otosclerosis in two large independent case‐control sets. We found significant association in both populations with BMP2 and BMP4, implicating these two genes in the pathogenesis of this disease. Introduction : Otosclerosis is a progressive disorder of the human temporal bone that leads to conductive hearing loss and in some cases sensorineural or mixed hearing loss. In a few families, it segregates as a monogenic disease with reduced penetrance, but in most patients, otosclerosis is more appropriately considered a complex disorder influenced by genetic and environmental factors. Materials and Methods : To identify major genetic factors in otosclerosis, we used a candidate gene approach to study two large independent case‐control sets of Belgian‐Dutch and French origin. Tag single nucleotide polymorphisms (SNPs) in 13 candidate susceptibility genes were studied in a stepwise strategy. Results : Two SNPs were identified that showed the same significant effect in both populations. The first SNP, rs3178250, is located in the 3′ untranslated region of BMP2. Individuals homozygote for the C allele are protected against otosclerosis (combined populations: p = 2.2 × 10^?4; OR = 2.027; 95% CI = 1.380–2.979). The second SNP, rs17563, is an amino acid changing (p.Ala152Val) SNP located in BMP4. The G allele, coding for the amino acid alanine, confers susceptibility in both populations (combined populations: p = 0.002; OR = 1.209; 95% CI: 1.070–1.370). Conclusions : These results indicate that polymorphisms in the BMP2 and BMP4 genes, both members of the TGF‐β superfamily, contribute to the susceptibility to otosclerosis and further strengthen the results from the recently reported association of TGFB1 with this disease.     

Negative Posttrauma Cognitions Mediate the Association Between Morally Injurious Events and Trauma‐Related Psychopathology in Treatment‐Seeking Veterans

Exposure to potentially morally injurious events has been shown to be associated with posttraumatic stress disorder (PTSD) and depression symptoms in military personnel. Few studies have examined factors that help to explain how potentially morally injurious events may contribute to the development of trauma‐related psychopathology. Negative posttrauma cognitions are thought to play a role in the etiology of PTSD and depression following trauma; however, it is unclear whether more global beliefs about the self, others, and world play a role in the development of PTSD and depression due to morally injurious events. Using structural equation modeling, we tested whether morally injurious experiences were indirectly related to trauma‐related psychopathology (PTSD and depression) through negative posttrauma cognitions in a sample of veterans seeking treatment for PTSD. An indirect effects only model best fit the data and showed that morally injurious experiences, specifically perceived transgressions by oneself and perceived betrayal, were indirectly associated with trauma‐related psychopathology through negative posttrauma cognitions, β = .17; 95% CI [.04, .31] and β = .25; 95% CI [.11, .41], respectively. Our findings suggest that negative posttrauma cognitions may be an important mechanism linking exposure to morally injurious events and trauma‐related psychopathology.     

Numbing of Positive,Negative, and General Emotions: Associations With Trauma Exposure,Posttraumatic Stress,and Depressive Symptoms Among Justice‐Involved Youth

Increasing attention has been drawn to the symptom of emotional numbing in the phenomenology of posttraumatic stress disorder (PTSD), particularly regarding its implications for maladaptive outcomes in adolescence such as delinquent behavior. One change in the definition of emotional numbing according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM‐5; American Psychiatric Association, 2013) was the limitation to the numbing of positive emotions. Previous research with youth, however, has implicated general numbing or numbing of negative emotions in PTSD, whereas numbing of positive emotions may overlap with other disorders, particularly depression. Consequently, the goal of this study was to investigate whether numbing of positive emotions was associated with PTSD symptoms above and beyond numbing of negative emotions, general emotional numbing, or depressive symptoms among at‐risk adolescents. In a sample of 221 detained youth (mean age = 15.98 years, SD = 1.25; 50.7% ethnic minority), results of hierarchical multiple regressions indicated that only general emotional numbing and numbing of anger accounted for significant variance in PTSD symptoms (total R² = .37). In contrast, numbing of sadness and positive emotions were statistical correlates of depressive symptoms (total R² = .24). Further tests using Hayes’ Process macro showed that general numbing, 95% CI [.02, .45], and numbing of anger, 95% CI [.01, .42], demonstrated indirect effects on the association between trauma exposure and PTSD symptoms.     

Predictors of Treatment Completion for Families Referred to Trauma‐Focused Cognitive Behavioral Therapy After Child Abuse

Despite advances in the dissemination of evidence‐based therapy for abuse‐related traumatic stress, many referred children fail to complete treatment. Using archival data from a sample of children participating in trauma‐focused cognitive behavioral therapy (TF‐CBT) at a hospital‐based child advocacy center, analyses explored the impact of baseline child traumatic stress symptoms, a second (nonprimary) caregiver's treatment attendance, and the number of assessment sessions on treatment completion while controlling for demographic variables. We conducted analyses separately for the total sample (n = 77) and for a subsample of children 6 years of age or older (n = 65) who completed measures of traumatic stress. Families who completed TF‐CBT had fewer pretreatment assessment sessions, odds ratio (OR) = 0.41, 95% CI [0.19, 0.88], and greater nonprimary caregiver session attendance, OR = 1.30, 95% CI [1.03, 1.64], than families who did not complete treatment. Child age, race, and insurance status did not predict treatment completion. Among children at least 6 years of age, treatment completion was related to younger child age, OR = 0.76, 95% CI [0.59, 0.98], and fewer diagnostic evaluation sessions, OR = 0.29, 95% CI [0.11, 0.74], but not to baseline traumatic stress symptoms. Findings may suggest benefits of shortening the assessment period and including a second caregiver in TF‐CBT.     

Pretrauma Power and Control Beliefs and Posttraumatic Stress: A Longitudinal Study of Combat Soldiers

Belief in one's ability to exert power and control over outcomes following trauma has long been understood as protective against the development of posttraumatic stress disorder (PTSD). The role of pretrauma beliefs about power and control, however, remains unclear. Though a strong pretrauma belief in power and control may similarly be protective, we predicted such a belief may actually be a diathesis for PTSD. When exposed to trauma, individuals with a strong pretrauma belief in power and control may believe they should have prevented the trauma and/or their acute reactions. Such expectations may lead to negative self‐beliefs and a higher level of PTSD symptoms. Longitudinal structural equation modeling in a sample of combat soldiers (N = 305) supported our hypothesized model. Stronger predeployment power and control beliefs predicted more negative postdeployment self‐beliefs, β = .15, p = .035, 95% CI [.11, .18], and in turn, a higher level of PTSD symptoms, β = .08, 95% CI [.01, .15]. Prior combat exposure moderated these effects in that soldiers with no prior combat experience evidenced the hypothesized associations, whereas those with moderate or high prior combat exposure did not. Resilience interventions for soldiers who are first entering combat may thus benefit from promoting acceptance of uncontrollable events in addition to agentic change skills.     

The Complex Trauma Inventory: A Self‐Report Measure of Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder

The work group revising the criteria for trauma‐related disorders in the International Classification of Diseases (ICD‐11) made several changes. Specifically, they simplified the criteria for posttraumatic stress disorder (PTSD) and added a new trauma disorder called complex PTSD (CPTSD). These proposed changes to taxonomy require new instruments to assess these novel constructs. We developed a measure of PTSD and CPTSD (the Complex Trauma Inventory; CTI) according to the proposed domains, creating several items to assess each domain. We examined the factor structure of the CTI in two separate samples of diverse college students (n ₁ = 391; n ₂ = 391) who reported exposure to at least one traumatic event and at least occasional functional impairment. After reducing the original 50 items in the item pool to 20 items, confirmatory factor analyses supported two highly correlated second‐order factors—PTSD and disturbances in self‐organization (DSO)—with PTSD (i.e., reexperiencing, avoidance, sense of threat) and DSO (i.e., affect dysregulation, negative self‐concept, and disturbances in relationships), each loading on three of the six ICD‐11‐consistent first‐order factors, root mean square error of approximation (RMSEA) = .056, 95% confidence interval (CI) [.048, .064], comparative fit index (CFI) = .956, Tucker‐Lewis index (TLI) = .948, standardized root mean square residual (SRMR) = .043, Bayesian information criterion (BIC) = 641.55, χ²(163) = 361.02, p < .001. Internal consistencies for PTSD and DSO were good to excellent (Cronbach's αs = .89 to .92). Supplementary analyses supported the gender invariance of the CFA model, as well as convergent and discriminant validity of the CTI. The validity of the CTI supports the distinction between CPTSD and PTSD. Moreover, the CTI will assist clinicians with diagnosis, symptom tracking, treatment planning, and assessing outcomes.     

Is Viewing Mass Trauma Television Coverage Associated With Trauma Reactions in Adults and Youth? A Meta‐Analytic Review

This study presents the findings of meta‐analyses examining the association between viewing mass trauma television coverage and posttraumatic stress (PTS) outcomes as well as acute stress reactions (ASR) among adults and youth. A literature search identified 43 (N = 31,162) studies assessing the association between viewing mass trauma television coverage and PTS and four (N = 9,083) assessing the association with ASR. The overall size of the association between viewing television coverage and PTS, estimated using a random‐effect model, was small but statistically significant, r = .17, 95% CI [.13, .22]. The moderator analysis examined eight preselected variables: man‐made versus natural trauma, specific incident versus chronic stressor, adult versus youth sample, proximal versus distal event exposure, television only versus combined media form, specific content in coverage versus no specific content, quantification of media contact using numeric measurement versus subjective measurement versus a binary item, and posttraumatic stress symptoms (PTSS) versus posttraumatic stress disorder (PTSD) outcome. The analysis revealed a statistically significant moderation effect for the quantification of media contact (numeric vs. subjective vs. binary) only, which accounted for 19% of the observed heterogeneity. With a summary estimate of r = .26, 95% CI [.06, .44], the analysis of the ASR studies corroborated the PTS findings. The results suggest that clinicians and public health practitioners should discuss mass trauma television viewing with their patients and with the public. Limitations of the extant research are discussed.     

Exposure to traumatic events among treatment‐seeking,alcohol‐dependent women and men without PTSD

The authors examined lifetime exposure to a range of traumatic events in 106 abstinent, treatment‐engaged (85% residential; 15% outpatient), alcohol‐dependent women (n = 53) and men without current or lifetime posttraumatic stress disorder. Alcohol‐dependent women reported greater severity of childhood trauma, but similar lifetime exposure to traumatic events compared with men. Alcohol‐dependent women without cocaine abuse or TB (n = 10) reported greater severity of childhood trauma than women with (n = 43), and men with (n = 21) or without (n = 32) cocaine abuse or dependence. Results extend previously observed gender differences in trauma histories among alcohol‐dependent adults and point to potential gender‐ and substance‐specific drug coaddiction effects that may have been influenced by trauma exposure.     

Exposure to Childhood Abuse and Later Substance Use: Indirect Effects of Emotion Dysregulation and Exposure to Trauma

Little is known about how emotion dysregulation (ED) and trauma exposure differentially affect the relationship between abuse in childhood and adult substance use. We examined associations between child abuse, trauma exposure, ED, and current substance use in an already existing dataset. Participants (N = 2,014 adults, 90% African American) had been recruited from an urban hospital for a parent study. Analyses showed that drug and alcohol use was significantly positively correlated with child abuse (emotional, physical, and sexual), later trauma exposure, and ED (all ps < .001). Linear regression showed that exposure to abuse when older than a child was significantly associated with drug and alcohol use independent of child abuse and demographic variables (R²Δ = .08, p < .001; R²Δ = .04, p < .001). ED was significantly associated with drug and alcohol use independently of child abuse, nonabuse trauma, and demographic variables (R²Δ = .02, p < .001; R²Δ = .04, p < .001). Multiple mediation analyses showed that ED and later trauma exposure accounted for variance in the association between emotional abuse and substance use (p < .001). A better understanding of vulnerabilities to additional traumatization and emotion‐regulation deficits in individuals who have been exposed to child abuse and in addition have comorbid substance use problems may inform treatments that lead to improved outcomes.     

A Meta‐Analysis of the Association Between Appraisals of Trauma and Posttraumatic Stress in Children and Adolescents

Cognitive models of posttraumatic stress disorder (PTSD) place an emphasis on the role of negative appraisals of traumatic events. It is suggested that the way in which the event is appraised determines the extent to which posttraumatic stress symptoms will be experienced. Therefore, a strong relationship between trauma appraisals and symptoms of PTSD might be expected. However, this relationship is not as firmly established in the child and adolescent literature. A systematic literature review of this relationship returned 467 publications, of which 11 met full eligibility criteria. A random effects meta‐analysis revealed a large effect size for the relationship between appraisals and PTSD symptoms in children and adolescents, r = .63, 95% CI [.58, .68], Z = 17.32, p < .001, with significant heterogeneity present. A sensitivity analysis suggested that this relationship was not contingent on 1 specific measure of appraisals. Results were consistent with the cognitive behavioral theory of PTSD, demonstrating that appraisals of trauma are strongly related to posttraumatic stress in children and adolescents. However, this relationship was not observed in a sample of 4‐ to 6‐year‐olds, indicating that further research is required to explicate cognitive processing of trauma in very young children.     

Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors

BackgroundArthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA).MethodsWe performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants.ResultsAmong 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00–2.20], had a more recent transition into menopause (<10 years) (5–10 years AOR 1.55, 95% CI 1.09–2.22; <5 years AOR 1.78, 95% CI 1.18–2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08–2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02–1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55–3.16).ConclusionsTime since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors.     

Relevance of the ACTN4 Gene in African-Americans with Non-Diabetic End-Stage Renal Disease

Background: African-Americans (AAs) are predisposed to non-diabetic (non-DM) end-stage renal disease (ESRD), and studies have shown a genetic component to this risk. Rare mutations in ACTN4 (α-actinin-4), an actin-binding protein expressed in podocytes, cause familial focal segmental glomerulosclerosis. Methods: We assessed the contribution of coding variants in ACTN4 to non-DM ESRD risk in AAs. Nineteen exons, 2,800 bases of the promoter and 392 bases of the 3' untranslated region of ACTN4 were sequenced in 96 AA non-DM ESRD cases and 96 non-nephropathy controls (384 chromosomes). Sixty-seven single-nucleotide polymorphisms (SNPs) including 51 novel SNPs were identified. The SNPs comprised 33 intronic, 21 promoter, 12 exonic, and one 3' variant. Sixty-two of the SNPs were genotyped in 296 AA non-DM ESRD cases and 358 non-nephropathy controls. Results: One SNP, rs10404257, was associated with non-DM ESRD (p < 1.0E-4, odds ratio, OR = 0.76; confidence interval, CI = 0.59-0.98; additive model). Forty-seven SNPs had minor allele frequencies <5%. These SNPs were segregated into risk and protective SNPs, and each category was collapsed into a single marker, designated by the presence or absence of any rare allele. The presence of any rare allele at a risk SNP was significantly associated with non-DM ESRD (p = 0.001, dominant model). The SNPs with the strongest evidence for association (n = 20) were genotyped in an independent set of 467 non-DM ESRD cases and 279 controls. Although rs10404257 was not associated in this replication sample, when the samples were combined, rs10404257 was modestly associated (p = 0.032, OR = 0.78, CI = 0.63-0.98; dominant model). SNPs were tested for interaction with markers in the APOL1 gene, previously associated with non-DM ESRD in AAs, and rs10404257 was modestly associated (p = 0.0261, additive model). Conclusions: This detailed evaluation of ACTN4 variation revealed limited evidence of association with non-DM ESRD in AAs.     

Risk for Revictimization Following Interpersonal and Noninterpersonal Trauma: Clarifying the Role of Posttraumatic Stress Symptoms and Trauma‐Related Cognitions

One victimization experience can increase the risk for subsequent victimization, which is known as revictimization. The aims of this study were to build on sexual revictimization research by (a) broadening the understanding of revictimization to interpersonal (and potentially noninterpersonal) trauma generally and (b) gaining specificity in the mechanisms that underlie revictimization. Using a prospective multisite design, an ethnically and racially diverse sample of 453 young women from the community (age range: 18–25 years, 60.7% European American) completed an initial survey and at least one follow‐up survey within the subsequent year. Participants completed self‐report measures of trauma history, posttraumatic stress symptoms, and maladaptive posttraumatic cognitions. Structural equation models revealed that interpersonal revictimization was observed when controlling for past noninterpersonal trauma, odds ratio (OR) = 2.27, 95% CI [1.23, 4.18], and supported the role of posttraumatic stress symptoms as a mechanism underlying such revictimization, 95% CI of indirect effect (IE) [0.08, 0.51]. Additionally, a history of noninterpersonal trauma (controlling for past interpersonal trauma) increased risk of subsequent interpersonal victimization via posttraumatic stress symptoms, 95% CI of IE [0.01, 0.38]. Notably, however, when maladaptive cognitions were included as mediators in addition to posttraumatic stress symptoms, the only unique indirect effect was for the association between interpersonal trauma and risk of revictimization specifically through perceived threat of harm, 95% CI of IE [0.05, 0.20]. These findings suggest that efforts to reduce interpersonal revictimization should target maladaptive posttraumatic cognitions, particularly perceptions of threat in the environment.     

A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians

IntroductionMultiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown.Materials and methodsIn this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP “cases” (n = 392) and clinically evaluated “controls” (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05.ResultsWe showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37–2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41–3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59–3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73–1.11], P> 0.05.ConclusionThus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population.