Genome-wide association study of posttraumatic stress disorder among childhood cancer survivors : results from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort

Funding Information: This work was supported by the National Cancer Institute (CA55727, G.T. Armstrong, Principal Investigator). The St. Jude Lifetime Cohort study was supported by the National Cancer Institute (U01CA195547, M.M. Hudson/L.L. Robison, Principal Investigators). Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese-Syrian Associated Charities (ALSAC). Dr. Lu was supported by a research fellowship at the Dana-Farber Cancer Institute funded by the Swim Across America and the Grant of Excellence from the Icelandic Research Fund (163362-051 to Dr. Valdimarsdóttir). Open access funding provided by Karolinska Institute. Publisher Copyright: © 2022, The Author(s).Genetic influence shapes who develops posttraumatic stress disorder (PTSD) after traumatic events. However, the genetic variants identified for PTSD may in fact be associated with traumatic exposures (e.g., interpersonal violence), which appear heritable as well. Childhood cancer survivors (CCS) are at risk for PTSD, but genetic influences affecting cancer are unlikely to overlap with those affecting PTSD. This offers a unique opportunity to identify variants specific to PTSD risk. In a genome-wide association study (GWAS), 3984 5-year survivors of childhood cancer of European-ancestry from the Childhood Cancer Survivor Study (CCSS) were evaluated for discovery and 1467 survivors from the St. Jude Lifetime (SJLIFE) cohort for replication. Childhood cancer-related PTSD symptoms were assessed using the Posttraumatic Stress Diagnostic Scale in CCSS. GWAS was performed in CCSS using logistic regression and lead markers were replicated/meta-analyzed using SJLIFE. Cross-associations of identified loci were examined between CCS and the general population. PTSD criteria were met for 671 participants in CCSS and 161 in SJLIFE. Locus 10q26.3 was significantly associated with PTSD (rs34713356, functionally mapped to ECHS1, P = 1.36 × 10–8, OR 1.57), and was replicated in SJLIFE (P = 0.047, OR 1.37). Variants in locus 6q24.3-q25.1 reached marginal significance (rs9390543, SASH1, P = 3.56 × 10–6, OR 0.75) in CCSS and significance when meta-analyzing with SJLIFE (P = 2.02 × 10–8, OR 0.75). Both loci were exclusively associated with PTSD in CCS rather than PTSD/stress-related disorders in general population (P-for-heterogeneity < 5 × 10–6). Our CCS findings support the role of genetic variation in PTSD development and may provide implications for understanding PTSD heterogeneity.Peer reviewe

Identifying suicidal symptoms in prostate cancer survivors using brief self-report

Abstract Purpose Prostate cancer (PC) survivors are at elevated risk for completed suicide even many years post-treatment. Despite this risk, practical and efficient methods for assessing these symptoms have not been established. We sought to determine if suicidal symptoms could be effectively and efficiently identified in a cohort of PC survivors, and whether these men were receptive to emotional health interventions.Methods Six hundred fifty-six PC survivors, an average of 5 years post-diagnosis, completed eight self-report items about suicidal symptoms and behavior in the past 7 days, and 12 months, as well as medical utilization and interest in emotional health support. Results Between 3.6 and 17.9 % of PC survivors endorsed a single suicidal ideation item, and denied all other ideation. All survivors who endorsed serious suicidal ideation/behavior also endorsed either passive or active ideation. 58.3 % of survivors denied any suicidal symptoms within the past week, but endorsed it within the past year. Most survivors had medical provider contact within the past year and were open to receiving information about emotional health interventions. Conclusions Suicidal ideation in PC survivors cannot be accurately evaluated using only a one-item screen, or by inquiring within a single time frame. Implications for Cancer Survivors In both research and clinical settings, the evaluation for suicidal ideation in PC survivors should utilize multiple questions, across several time periods. It is possible to skip queries about serious ideation/ behavior if passive or active ideation is denied. Once identified, medical providers should refer these men to psychosocial providers who can offer emotional support

Identifying suicidal symptoms in prostate cancer survivors using brief self-report

AbstractPurposeProstate cancer (PC) survivors are at elevated risk for completed suicide even many years post-treatment. Despite this risk, practical and efficient methods for assessing these symptoms have not been established. We sought to determine if suicidal symptoms could be effectively and efficiently identified in a cohort of PC survivors, and whether these men were receptive to emotional health interventions.MethodsSix hundred fifty-six PC survivors, an average of 5 years post-diagnosis, completed eight self-report items about suicidal symptoms and behavior in the past 7 days, and 12 months, as well as medical utilization and interest in emotional health support.ResultsBetween 3.6 and 17.9 % of PC survivors endorsed a single suicidal ideation item, and denied all other ideation. All survivors who endorsed serious suicidal ideation/behavior also endorsed either passive or active ideation. 58.3 % of survivors denied any suicidal symptoms within the past week, but endorsed it within the past year. Most survivors had medical provider contact within the past year and were open to receiving information about emotional health interventions.ConclusionsSuicidal ideation in PC survivors cannot be accurately evaluated using only a one-item screen, or by inquiring within a single time frame.Implications for Cancer SurvivorsIn both research and clinical settings, the evaluation for suicidal ideation in PC survivors should utilize multiple questions, across several time periods. It is possible to skip queries about serious ideation/behavior if passive or active ideation is denied. Once identified, medical providers should refer these men to psychosocial providers who can offer emotional support.KeywordsSuicide ideation Prostate cancer Cancer survivorship9 halama

Psychological symptoms, social outcomes, socioeconomic attainment, and health behaviors among survivors of childhood cancer: Current state of the literature

The diagnosis, treatment, and medical late effects of childhood cancer may alter the psychosocial trajectory of survivors across their life course. This review of the literature focuses on mental health symptoms, achievement of social milestones, socioeconomic attainment, and risky health behaviors in survivors of childhood cancer. Results suggest that although most survivors are psychologically well adjusted, survivors are at risk for anxiety and depression compared with siblings. Although the absolute risk of suicide ideation and post-traumatic stress symptoms is low, adult survivors are at increased risk compared with controls. Moreover, young adult survivors are at risk for delayed psychosexual development, lower rates of marriage or cohabitation, and nonindependent living. Survivors’ socioeconomic attainment also is reduced, with fewer survivors graduating college and gaining full-time employment. Despite risk for late health-related complications, survivors of childhood cancer generally engage in risky health behaviors at rates similar to or only slightly lower than siblings and peers. CNS tumors and CNS-directed therapies are salient risk factors for poor psychosocial outcomes. In addition, physical health morbidities resulting from cancer-directed therapies are associated with worse psychosocial functioning. Several studies support the effectiveness of cognitive and behavioral interventions to treat psychological symptoms as well as to modify health behaviors. Additional randomized controlled trials are needed to evaluate the efficacy and long-term outcomes of intervention efforts. Future research should focus on the identification of potential genetic predispositions related to psychosocial outcomes to provide opportunities for preventive interventions among survivors of childhood cancer