Psychiatric disorders, such as schizophrenia, depression, anxiety, and bipolar disorder, are common conditions that arise as a result of complex and heterogeneous combinations of genetic and ...environmental factors. In contrast to childhood neurodevelopmental conditions such as autism and intellectual disability, there are no clinical practice guidelines for applying genetic testing in the context of these conditions. But genetic counseling and genetic testing are not synonymous, and people who live with psychiatric disorders and their family members are often interested in what psychiatric genetic counseling can offer. Further, research shows that it can improve outcomes like empowerment for this population. Despite this, psychiatric genetic counseling is not yet routinely or widely offered. This review describes the state of the evidence about the process and outcomes of psychiatric genetic counseling, focusing on its clinical implications and remaining research gaps.
Little data currently exist regarding whether and how different characteristics of a patient and session influence outcomes of genetic counseling (GC). We conducted an exploratory retrospective chart ...review of data from a specialist psychiatric GC clinic (where patients complete the Genetic Counseling Outcome Scale (GCOS) as part of routine care before and after GC). We used ANOVA and linear regression to analyze GCOS change scores in relation to twelve patient/session-related variables. Three hundred and seven charts were included in analyses. Overall, GCOS scores increased significantly after GC, with large effect size (p < 0.0005, d = 1.10), and significant increases in all GCOS subdomains except adaptation. Significant associations with GCOS change score were identified for three variables: mode of delivery of GC (in-person/telephone/telehealth, p = 0.048, η
= 0.020), primary indication for the appointment (understanding recurrence risk versus other primary indications, p = 0.001, η
= 0.037), and baseline GCOS score (p < 0.000, R = 0.353). Our data showing that those with low baseline GCOS scores benefit most from GC could be used to explore the possibility of triaging those referred for GC based on this variable, and/or to identify individuals to refer to GC.
We sought to explore individuals' motivations for using their direct-to-consumer genetic testing data to generate polygenic risk scores (PRSs) using a not-for-profit third-party tool, and to assess ...understanding of, and reaction to their results. Using a cross-sectional design, users of Impute.me who had already accessed PRS results were invited to complete an online questionnaire asking about demographics, motivations for seeking PRSs, understanding and interpretation of PRSs, and two validated scales regarding reactions to results-the Impact of Event Scale Revised (IES-R) and the Feelings About genomiC Testing Results (FACToR). Independent samples T-tests and ANOVA were used to explore associations between the variables. 227 individuals participated in the study. The most frequently reported motivation was general curiosity (98.2%). Only 25.6% of participants correctly answered all questions assessing understanding/interpretation of PRSs. Over half of participants (60.8%) experienced a negative reaction (upset, anxious, and/or sad on FACToR scale) after receiving their PRSs and 5.3% scored over the threshold for potential post-traumatic stress disorder on the IES-R. Lower understanding about PRS was associated with experiencing a negative psychological reaction (P values <0.001). Higher quality pre-test information, particularly to improve understanding, and manage expectations for PRS may be useful in limiting negative psychological reactions.
An abundance of qualitative research is being conducted within the genetic counseling field. As this area of research expands, many within our community are “learning through doing”, an approach ...which is practical, but may lack theoretical grounding. This can result in study outputs that do not have the sort of utility for informing clinical practice that is the hallmark of excellent clinical qualitative research. Furthermore, our alignment as a discipline within the health sciences, which still tends to favor quantitative approaches, means that we may often be obliged to justify the use of qualitative methodologies, especially when we intend to use the findings for informing clinical practice. We aim to address these issues by providing guidance about how we, individually and collectively, might think about what excellent qualitative research can look like in our field. In addition to providing information and resources about current best‐practices, we discuss how quality can be ensured and evaluated. We seek to legitimize the idea of developing a philosophy of research in pursuit of establishing genetic counseling as an academic discipline. We argue that the principles, ethics, values, and practices of genetic counseling are sufficiently unique that establishing a discipline‐specific qualitative research framework is not only warranted, but essential. Ultimately, we hope that this paper can serve as a launching point from which additional discussion about qualitative research can emanate as we strive towards the elevation of this form of inquiry in our field.
There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score ...predictions on the absolute scale is an important step for their safe interpretation. We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R
) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. We also evaluate methods for estimating polygenic score AUC/R
from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R
estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. When the AUC/R
of the polygenic score is known, the observed and estimated absolute values were highly concordant. Estimates of AUC/R
from the lassosum pseudovalidation method were most similar to the observed AUC/R
values, though estimated values deviated substantially from the observed for autoimmune disorders. This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute ( https://opain.github.io/GenoPred/PRS_to_Abs_tool.html ). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.
Objectives
With increasing evidence for the clinical utility of pharmacogenomic (PGx) testing for depression, there is a growing need to consider issues related to the clinical implementation of this ...testing. The perspectives of key stakeholders (both people with lived experience PWLE and providers) are critical, but not frequently explored. The purpose of this study was to understand how PWLE and healthcare providers/policy experts (P/HCPs) perceive PGx testing for depression, to inform the consideration of clinical implementation within the healthcare system in British Columbia (BC), Canada.
Methods
We recruited two cohorts of participants to complete individual 1-h, semi-structured interviews: (a) PWLE, recruited from patient and research engagement networks and organizations and (b) P/HCPs, recruited via targeted invitation. Interviews were audiotaped, transcribed verbatim, de-identified, and analysed using interpretive description.
Results
Seventeen interviews were completed with PWLE (7 with experience of PGx testing for depression; 10 without); 15 interviews were completed with P/HCPs (family physicians, psychiatrists, nurses, pharmacists, genetic counsellors, medical geneticists, lab technologists, program directors, and insurers). Visual models of PWLE's and P/HCP's perceptions of and attitudes towards PGx testing were developed separately, but both were heavily influenced by participants’ prior professional and/or personal experiences with depression and/or PGx testing. Both groups expressed a need for evidence and numerous considerations for the implementation of PGx testing in BC, including the requirement for conclusive economic analyses, patient and provider education, technological and clinical support, local testing facilities, and measures to ensure equitable access to testing.
Conclusions
While hopeful about the potential for therapeutic benefit from PGx testing, PWLE and P/HCPs see the need for robust evidence of utility, and BC-wide infrastructure and policies to ensure equitable and effective access to PGx testing. Further research into the accessibility, effectiveness, and cost-effectiveness of various implementation strategies is needed to inform PGx testing use in BC.
Prenatal and early postnatal exposure to maternal depression may "program" childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an ...important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.
Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2(nd) and 3(rd) trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2(nd) trimester depressed mood (p<0.05). Increased 2(nd) trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.
These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.
Genetic counseling globally: Where are we now? Ormond, Kelly E.; Laurino, Mercy Ygoña; Barlow‐Stewart, Kristine ...
American journal of medical genetics. Part C, Seminars in medical genetics,
March 2018, 2018-03-00, Letnik:
178, Številka:
1
Journal Article
Odprti dostop
The genetic counseling profession is continuing to develop globally, with countries in various stages of development. In some, the profession has been in existence for decades and is increasingly ...recognized as an important provider of allied health, while in others it is just beginning. In this article, we describe the current global landscape of the genetic counseling specialty field's professional development. Using examples of the United States, United Kingdom, Canada, Australia, South Africa, and various countries in Asia, we highlight the following: (a) status of genetic counseling training programs, (b) availability of credentialing through government and professional bodies (certification, registration, and licensure), and potential for international reciprocity, (c) scope of clinical practice, and (d) health‐care system disparities and cultural differences impacting on practice. The successful global implementation of precision medicine will require both an increased awareness of the importance of the profession of “genetic counselor” and flexibility in how genetic counselors are incorporated into each country's health‐care market. In turn, this will require more collaboration within and across nations, along with continuing engagement of existing genetic counseling professional societies.
•Safe disclosure may allow for earlier school supports and improve functioning.•Education about obsessive-compulsive disorder can increase disclosure in schools.•A safe space allows youth to ...determine their individualized disclosure boundaries.•Deep and reciprocal connections increase trust and the subsequent details shared.•Confidential and personalized supports empower a youth after a disclosure.
Disclosure of an OCD diagnosis in the high school setting could allow for timely provision of individualized school-based supports. As few studies have examined adolescent perspectives on the disclosure process in schools, we adopted a qualitative approach to explore this, and to gather recommendations for making disclosure of OCD at school safer and more helpful. Twelve participants, ranging from 13 to 17 years old, were recruited using maximum variance-based heterogeneous purposive sampling. Semi-structured interviews were conducted and analyzed inductively through Interpretive Description. From participants’ stories, we generated a theoretical model describing the journey from concealment of an OCD diagnosis to disclosure. Four phases of youth disclosure were identified: managing enacted and perceived stigma related to the diagnosis, internal bargaining to determine their individualized disclosure boundaries, trust building with school members, and empowerment by being treated as a person first. Participants’ recommendations for the school setting included meaningful education, safe spaces, deep reciprocal connections, and confidential personalized support. The model we developed can help inform school disclosure strategies and optimize support to promote best outcomes for youth with OCD.
In this session, we will consider the application of genetic counseling in the context of psychiatric conditions. We will distinguish between genetic counseling and genetic testing, review the ...evidence regarding the outcomes of genetic counseling for psychiatric conditions and consider implications for psychiatric genetic testing. The goal of this session is to help clinicians feel confident and competent in having impactful and meaningful conversations with their patients about the relevance of genetics in the context of their own psychiatric condition.
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