Reading List

Potter-Dickey, A., Letourneau, N., Ntanda, H., Giesbrecht, G., Silveira, P. P., Dewell, S., & de Koning, A. P. J. Associations Among Parental Caregiving Quality, Cannabinoid Receptor 1 Expression-Based Polygenic Scores, and Infant-Parent Attachment: Evidence for Differential Genetic Susceptibility? Front Neurosci. 2021 Jul 27;15:704392. doi: 10.3389/fnins.2021.704392. PMID: 34385904; PMCID: PMC8353245. 

Abstract

Attachment is a biological evolutionary system contributing to infant survival. When primary caregivers/parents are sensitive and responsive to their infants’ needs, infants develop a sense of security. Secure infant attachment has been linked to healthy brain and organ-system development. Belsky and colleagues proposed the term differential susceptibility to describe context-dependent associations between genetic variations and behavioral outcomes as a function of parenting environments. Variations in the Cannabinoid Receptor Gene 1 (CNR1) are associated with memory, mood, and reward and connote differential susceptibility to more and less optimal parental caregiving quality in predicting children’s behavioral problems.

Aim: To determine if parental caregiving quality interacts with children’s expression-based polygenic risk score (ePRS) for the CNR1 gene networks in the prefrontal cortex, striatum, and hippocampus in predicting the probability of attachment security and disorganized attachment.

Design: Prospective correlational methods examined maternal-infant pairs (n = 142) from which infants provided DNA samples at 3 months. Parental caregiving quality was assessed via the Child Adult Relationship Experiment (CARE)-index at 6 months, and attachment security via the Strange Situation Procedure at a mean age of 22 months. The CNR1 ePRSs include genes co-expressed with the CNR1 genes in the prefrontal cortex, striatum, or hippocampus, and were calculated using the effect size of the association between the individual single nucleotide polymorphisms from those genes and region-specific gene expression (GTEx). Logistic regression was employed (alpha < 0.05, two-tailed) to examine the main and interaction effects between parental caregiving quality and ePRSs in predicting attachment patterns. Interpretation of results was aided by analyses that distinguished between differential susceptibility and diathesis-stress.

Results: Significant interactions were observed between (1) maternal sensitivity and ePRS in the striatum in predicting attachment security, (2) maternal unresponsiveness with the ePRS in the hippocampus in predicting disorganization, and (3) maternal controlling with the ePRS in the hippocampus in predicting disorganization.

Conclusion: These findings offer support for genetic differential susceptibility to the quality of maternal sensitivity in the context of the ePRS in the striatum. However, the significant interactions between hippocampal ePRS and maternal unresponsiveness and controlling in predicting the probability of disorganization were more suggestive of the diathesis-stress model.

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Letourneau, N., Giesbrecht, G. F., Bernier, F. P., & Joschko, J. (2014). How do interactions between early caregiving environment and genes influence health and behavior? Biological Research for Nursing, 16(1), 83-94. https://doi.org/10.1177/1099800412463602

Abstract

To promote optimal health and behavioral outcomes in children, nurses have long supported parents in providing the best possible care and nurturance to their offspring. A growing body of neuroscience research argues convincingly for the combined influences of genes and early caregiving on producing an individual’s unique health and behavioral phenotype. In this article, we systematically review studies that demonstrate the relationship between qualities of early caregiving and genetic propensity to health and behavioral outcomes. From an initial set of 255 articles, 24 articles met our inclusion criteria. The outcomes fall into four distinct groups: hypothalamic-pituitary-adrenal (HPA) response to stress, externalizing behavior, internalizing behavior, and disorganized attachment. In the articles, authors examined genes that code for the 5-hydroxytryptamine (serotonin) transporter genes linked polymorphic region [5-HTTLPR] serotonin transporter promoter, D4 dopamine receptor, brain-derived neurotrophic factor, and monoamine oxidase A promoter. The reviewed studies suggest that the effect of the early rearing environment on gene expression relates mainly to HPA response to stress, whereas interactions between genes and caregiving mainly relate to behavior and attachment. Findings have implications for nurses focused on advocacy, prevention, and intervention to support the healthy development of children in families faced with adversity.

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Letourneau, Ntanda, H., Jong, V. L., Mahinpey, N., Giesbrecht, G., & Ross, K. M. (2021). Prenatal maternal distress and immune cell epigenetic profiles at 3‐months of age. Developmental Psychobiology, 63(5),

973–984. https://doi.org/10.1002/dev.22103 

Background 

Prenatal maternal distress predicts altered offspring immune outcomes, potentially via altered epigenetics. The role of different kinds of prenatal maternal distress on DNA methylation profiles is not understood. 

Methods 

A sample of 117 women (AprON cohort) were followed from pregnancy to the postpartum period. Maternal distress (depressive symptoms, pregnancy-specific anxiety, stressful life events) were assessed mid-pregnancy, late-pregnancy, and 3-months postpartum. DNA methylation profiles were obtained from 3-month-old blood samples. Principal component analysis identified two epigenetic components, characterized as Immune Signaling and DNA Transcription through gene network analysis. Covariates were maternal demographics, pre-pregnancy body mass index, child sex, birth gestational age, and postpartum maternal distress. Penalized regression 

(LASSO) models were used. 

Results 

Late-pregnancy stressful life events, b = 0.006, early-pregnancy depressive symptoms, b = 0.027, late-pregnancy depressive symptoms, b = 0.014, and pregnancy-specific anxiety during late pregnancy, b = −0.631, were predictive of the Immune Signaling component, suggesting that these aspects of maternal distress could affect 

methylation in offspring immune signaling pathways. Only early-pregnancy depressive symptoms was predictive of the DNA Transcription component, b = −0.0004, suggesting that this aspect of maternal distress is implicated in methylation of offspring DNA transcription pathways. 

Conclusions 

Exposure, timing and kind of prenatal maternal distress could matter in the prediction of infant immune epigenetic profiles. 

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Merrill, Gladish, N., Fu, M. P., Moore, S. R., Konwar, C., Giesbrecht, G. F., MacIssac, J. L., Kobor, M. S., & Letourneau, N. L. (2021). Associations of peripheral blood DNA methylation and estimated monocyte proportion differences during infancy with toddler attachment style. Attachment & Human Development, 1–30. https://doi.org/10.1080/14616734.2021.1938872

Abstract

Attachment is a motivational system promoting felt security to a caregiver resulting in a persistent internal working model of interpersonal behavior. Attachment styles are developed in early social environments and predict future health and development outcomes with potential biological signatures, such as epigenetic modifications like DNA methylation (DNAm). Thus, we hypothesized infant DNAm would associate with toddler attachment styles. An epigenome-wide association study (EWAS) of blood DNAm from 3-month-old infants was regressed onto children’s attachment style from the Strange Situation Procedure at 22-months at multiple DNAm Cytosine-phosphate-Guanine (CpG) sites. The 26 identified CpGs associated with proinflammatory immune phenotypes and cognitive development. In post-hoc analyses, only maternal cognitive-growth fostering, encouraging intellectual exploration, contributed. For disorganized children, DNAm-derived cell-type proportions estimated higher monocytes –cells in immune responses hypothesized to increase with early adversity. Collectively, these findings suggested the potential biological embedding of both adverse and advantageous social environments as early as 3-months-old.

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Letourneau, N. L. (2021). Paternal adverse childhood experiences: Associations with infant DNA methylation. Developmental Psychobiology, 63(6), e22174-n/a. https://doi.org/10.1002/dev.22174

Abstract

Adverse childhood experiences (ACEs), or cumulative childhood stress exposures, such as abuse, neglect, and household dysfunction, predict later health problems in both the exposed individuals and their offspring. One potential explanation suggests exposure to early adversity predicts epigenetic modification, especially DNA methylation (DNAm), linked to later health. Stress experienced preconception by mothers may

associate with DNAm in the next generation. We hypothesized that fathers’ exposure to ACEs also associates with their offspring DNAm, which, to our knowledge, has not been previously explored. An epigenome-wide association study (EWAS) of blood DNAm (n = 45) from 3-month-old infants was regressed onto fathers’ retrospective ACEs at multiple Cytosine-phosphate-Guanosine (CpG) sites to discover associations. This accounted for infants’ sex, age, ethnicity, cell type proportion, and genetic variability. Higher ACE scores associated with methylation values at eight CpGs. Posthoc analysis found no contribution of paternal education, income, marital status, and parental postpartum depression, but did with paternal smoking and BMI along with infant sleep latency. These same CpGs also contributed to the association between paternal ACEs and offspring attention problems at 3 years. Collectively, these findings suggested there were biological associations with paternal early life adversity and offspring DNAm in infancy, potentially affecting offspring later childhood outcomes.

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Letourneau, Ntanda, H., Jong, V. L., Mahinpey, N., Giesbrecht, G., & Ross, K. M. (2021). Prenatal maternal distress and immune cell epigenetic profiles at 3‐months of age. Developmental Psychobiology, 63(5), 973–984. https://doi.org/10.1002/dev.22103

Background

Prenatal maternal distress predicts altered offspring immune outcomes, potentially via altered epigenetics. The role of different kinds of prenatal maternal distress on DNA methylation profiles is not understood.

Methods

A sample of 117 women (APrON cohort) were followed from pregnancy to the postpartum period. Maternal distress (depressive symptoms, pregnancy-specific anxiety, stressful life events) were assessed mid-pregnancy, late-pregnancy, and 3-months postpartum. DNA methylation profiles were obtained from 3-month-old blood samples. Principal component analysis identified two epigenetic components, characterized as Immune Signaling and DNA Transcription through gene network analysis. Covariates were maternal demographics, pre-pregnancy body mass index, child sex, birth gestational age, and postpartum maternal distress. Penalized regression

(LASSO) models were used.

Results

late-pregnancy stressful life events, b = 0.006, early-pregnancy depressive symptoms, b = 0.027, late-pregnancy depressive symptoms, b = 0.014, and pregnancy-specific anxiety during late pregnancy, b = −0.631, were predictive of the Immune Signaling component, suggesting that these aspects of maternal distress could affect

methylation in offspring immune signaling pathways. Only early-pregnancy depressive symptoms was predictive of the DNA Transcription component, b = −0.0004, suggesting that this aspect of maternal distress is implicated in methylation of offspring DNA transcription pathways.

Conclusions

Exposure timing and kind of prenatal maternal distress could matter in the prediction of infant immune epigenetic profiles.

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Mighton, C., Carlsson, L., Clausen, M., Casalino, S., Shickh, S.,…Bombard, Y. (2019) Development of patient “profiles” to tailor counseling for incidental genomic sequencing results.  European Journal of Human Genetics 

Abstract 

Guidelines recommend that providers engage patients in shared decision-making about receiving incidental results (IR) prior to genomic sequencing (GS), but this can be time-consuming, given the myriad of IR and variation in patients’ preferences. We aimed to develop patient profiles to inform pre-test counseling for IR. We conducted semi-structured interviews with participants as a part of a randomized trial of the GenomicsADvISER.com, a decision aid for selecting IR. Interviews explored factors participants considered when deliberating over learning IR. Interviews were analyzed by thematic analysis and constant comparison. Participants were mostly female (28/31) and about half of them were over the age of 50 (16/31). We identified five patient profiles that reflect common contextual factors, attitudes, concerns, and perceived utility of IR. Information Enthusiasts self-identified as “planners” and valued learning most or all IR to enable planning and disease prevention because “knowledge is power”. Concerned Individuals defined themselves as “anxious,” and were reluctant to learn IR, anticipating negative psychological impacts from IR. Contemplators were discerning about the value and limitations of IR, weighing health benefits with the impacts of not being able to “un-know” information. Individuals of Advanced Life Stage did not consider IR relevant for themselves and primarily considered their implications for family members. Reassurance Seekers were reassured by previous negative genetic test results which shaped their expectations for receiving no IR: “hopefully [GS will] be negative, too. And then I can rest easy”. These profiles could inform targeted counseling for IR by providing a framework to address common values, concerns. and misconceptions.

 

Mighton, C., Carlsson, L., Clausen, M., Casalino, S., Shickh, S., & Bombard, Y. (2020) Quality of life drives patients’ preferences for incidental findings from genomic sequencing.  European Journal of Human Genetics 

Abstract  

There is growing impetus to include measures of personal utility, the nonmedical value of information, in addition to clinical utility in health technology assessment (HTA) of genomic tests such as genomic sequencing (GS). However, personal utility and clinical utility are challenging to define and measure. This study aimed to explore what drives patients’ preferences for hypothetically learning medically actionable and non-medically actionable secondary findings (SF), capturing clinical and personal utility; this may inform development of measures to evaluate patient outcomes following return of SF. Semistructured interviews were conducted with adults with a personal or family cancer history participating in a trial of a decision aid for selection of SF from genomic sequencing (GS) www.genomicsadviser.com 

Interviews were analyzed thematically using constant comparison. Preserving health-related and non-health-related quality of life was an overarching motivator for both learning and not learning SF. Some participants perceived that learning SF would help them “have a good quality of life” through informing actions to maintain physical health or leading to psychological benefits such as emotional preparation for disease. Other participants preferred not to learn SF because results “could ruin your quality of life,” such as by causing negative psychological impacts. Measuring health-related and non-health-related quality of life may capture outcomes related to clinical and personal utility of GS and SF, which have previously been challenging to measure. Without appropriate measures, generating and synthesizing evidence to evaluate genomic technology such as GS will continue to be a challenge, and will undervalue potential benefits of GS and SF. 

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Hébert, J., Bergeron, A. S., Veillette, A. M., Bouchard, K., Nabi, H., & Dorval, M. (2022). Issues associated with a hereditary risk of cancer: Knowledge, attitudes and practices of nurses in oncology settings. Canadian oncology nursing journal = Revue canadienne de nursing oncologique, 32(2), 272–285. https://doi.org/10.5737/23688076322272285

Abstract

Documenting a patient’s family history of cancer is useful in assessing their predisposition to some types of hereditary cancers. A group of nurses working with cancer patients were surveyed, by way of a questionnaire, to determine their level of knowledge about oncogenetics, describe various issues related to their capacity to identify, refer and support individuals with a hereditary risk of cancer, and explore their interest in continuing education on this topic. The findings show limited knowledge and a low sense of competence among the participating nurses, as well as a lack of access to university and continuing education programs in this field. Training focused on competency development would enhance their capacity to carry out an initial assessment of individuals who are potentially at risk for cancer and refer them to specialized resources.

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Manuel, A. & Brunger, F. (2014). Making the Decision to Participate in Predictive Genetic Testingor Arrhythmogenic Right Ventricular Cardiomyopathy. Journal of Genetic Counseling, 23(6), 1045–1055. https://doi.org/10.1007/s10897-014-9733-4

Abstract

This paper describes the experience of predictive genetic testing for Arrhythmogenic Right Ventricular Cardiomyopathy in the context of novel gene discovery. Two approaches to making the decision to engage in genetic testing were apparent: the decision to be tested either (a) develops gradually over time or (b) happens so quickly that it is felt as a “fait accompli.” Six key factors that influenced the particular approach taken by the participants were identified: (1) scientific process—available and relevant predictive genetic test; (2) numerous losses or deaths within the family; (3) physical signs and symptoms of disease; (4) gender; (5) sense of relational responsibility or moral obligation to other family members; and (6) family support. This study found that at risk individuals juxtapose scientific knowledge against their experiential knowledge and the six identified factors in order to make the decision to participate in genetic testing. Recommendations include the creation of a relational space within which to provide psychological counselling and assessment for the six identified factors that shape the decision to engage in predictive genetic testing.

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Manuel, & Brunger, F. (2015). “Awakening to” a new meaning of being at-risk for arrhythmogenic right ventricular cardiomyopathy: a grounded theory study. Journal of Community Genetics, 6(2), 167–175. https://doi.org/10.1007/s12687-015-0212-x

Abstract

Efforts of social scientists to understand how individuals living in a family at risk for a genetically linked condition make health care decisions, having brought to the forefront the contextual nature of risk perception. Using a grounded theory approach, this study examines the experiences of 29 individuals living in families at risk for arrhythmogenic right ventricular cardiomyopathy (ARVC). Attention is paid to how individuals (re)construct the meaning of being at risk in relation to the developing science of gene discovery. Findings highlight that individuals living in a family at risk for ARVC juxtapose existing scientific knowledge against experiential knowledge as they “awaken to” the fact that they or a family member are at risk. This process is pragmatic and fluid and contingent upon whether and how symptoms are aligned with the constructed image of the at-risk relative.

 

Manuel, & Brunger, F. (2016). Embodying a New Meaning of Being At Risk. Global Qualitative Nursing Research, 3, 2333393616674810–2333393616674810. https://doi.org/10.1177/2333393616674810

Abstract

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) is a genetic condition that can cause fatal arrhythmias. The implantable cardioverter defibrillation (ICD) is a primary treatment for ARVC/D. Using a grounded theory approach, this study examines the experiences of 15 individuals living with an ICD. The ability to cope with and adjust to having an ICD is influenced by the acceptance of the ICD as something needed to survive, an understanding of the ICD’s function, existing support networks, and ones’ ability to manage everyday challenges. Coping well requires reshaping ideas about the meaning of being at risk and understanding how the ICD fits into that changing personal risk narrative. A thorough understanding of the unique needs of individuals with ARVC/D and of the specific factors contributing to the psychosocial distress related to having an ICD (vs. having the disease itself) is needed. Nurses must be prepared to provide ongoing support and education to this population.

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Swadas, N., Dewell, S., & Davidson, S. (2022) "Knowledge and Attitudes of Pharmacogenetics Among Canadian Nurses: Implications for Nursing Education," Quality Advancement in Nursing Education - Avancées en formation infirmière: Vol. 8: Iss. 2, Article 3.
DOI: https://doi.org/10.17483/2368-6669.1319

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Abstract

Pharmacogenetic testing is used to tailor medication recommendations based on an individual's genetic makeup. Increased precision in prescribing medication through the use of genetics leads to a reduction in adverse drug reactions resulting in decreased morbidity and mortality. Due to the noted benefits to patient health outcomes and reduction in healthcare costs, a growing number of Canadian health centers and community pharmacies are beginning to offer pharmacogenetic testing. Previous studies indicate that Canadian nurses have minimal education in genomics; however, there has been an increase in attention to nursing roles in the implementation of genomic health practices in recent years. As the use of pharmacogenetics increases, nurses will be expected to be knowledgeable about pharmacogenetic testing and will play a key role in patient education. Results of previous studies show a low level of knowledge about pharmacogenetic testing among physicians and pharmacists; however, this area of knowledge has not been systematically assessed for nurses. To address this gap, a cross-sectional study was conducted to assess knowledge and attitudes about pharmacogenetics of nurses across Canada. An anonymous online survey was completed by 236 participants, including nursing students (n = 84), registered nurses (n = 144), and nurse practitioners/nurse clinicians (n = 9). Participants represented 9/10 provinces and 2/3 territories across Canada. The majority of the participants (65.9%) lacked formal education in genetics and indicated a fair or poor level of understanding of pharmacogenetic testing in the clinical setting (93%). The mean score for pharmacogenetic knowledge questions was 34.5%, while the mean score for genetics knowledge questions was 61.1%. Despite their self-reported lack of knowledge and understanding, most participants had positive attitudes towards pharmacogenetic testing and recognized its ability to decrease adverse drug reactions and improve clinical efficacy (81.3%). Most participants (73.7%) were interested in educational offerings related to pharmacogenetic testing, particularly web-based courses and seminars/lectures. The results of this study indicate that nurses across Canada may not have the necessary knowledge to support the implementation of pharmacogenetic testing into clinical practice. However, positive attitudes and interest in learning about pharmacogenetics indicate opportunities for the development of educational activities to ensure that Canadian nurses are prepared for upcoming changes that will impact nursing practice.