Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
In the originally published version of this article, Table 1 unfortunately included c.542G>A instead of c.542G>T. This mutation was correctly notated as c.
Background
Disturbances in emotion regulation and sleep are shared across anxiety and mood disorders. Poor sleep has been shown to impair cognitive processes which may undermine cognitive regulatory function. However, it remains unknown if sleep quality impacts regulatory mechanisms in clinical anxiety and depression.
Methods
During fMRI, 78 patients with social anxiety disorder, generalized anxiety disorder, and/or major depressive disorder completed a validated emotion regulation task, which involved reappraisal (i.e., decrease negative affect) as compared to viewing aversive images. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and actigraphy, representing subjective and objective measures of sleep, respectively. Regression analysis was conducted with the PSQI and actigraphy sleep efficiency, duration, and wake-after sleep onset variables.
Results
PSQI and actigraphy measures indicated that the majority of patients experienced problematic sleep, however, subjective and objective sleep measures were uncorrelated. Whole-brain voxel-wise regression analysis, controlling for diagnosis, revealed worse self-reported sleep corresponded with less reappraise-related activation in the dorsal anterior cingulate cortex (DACC). The same analysis performed with actigraphy data showed less sleep efficiency positively corresponded with DACC activation. Post-hoc stepwise regression analysis showed these sleep measures predicted DACC activity whereas anxiety and depression symptoms did not.
Conclusions
Individual differences in self-perceived and objective sleep quality differentially modulated the DACC, which is implicated in cognitive reappraisal. Findings suggest neural correlates of emotion regulation tracks different aspects of the sleep experience. Results also indicate sleep disturbance may play a role in the emotion dysregulation observed in anxiety and depressive disorders.
Introduction
As the number of Alzheimer's disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E (APOE) results efficiently, safely, and effectively in the context of AD prevention trials.
Methods
A multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer's Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials.
Results
The Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact.
Discussion
The API Genetic Counseling and Disclosure Process provides a framework for large‐scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological well‐being before and after APOE disclosure are still being collected and will be presented in a future publication.
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