Alex Wilde

Public interest in predictive genetic testing, including direct-to-consumer testing, for susceptibility to major depression: preliminary findings

The past decade has seen rapid advances in the identification of associations between candidate genes and a range of common multifactorial disorders. This paper evaluates public attitudes towards the complexity of genetic risk prediction in psychiatry involving susceptibility genes, uncertain penetrance and gene–environment interactions on which successful molecular-based mental health interventions will depend. A qualitative approach was taken to enable the exploration of the views of the public. Four structured focus groups were conducted with a total of 36 participants. The majority of participants indicated interest in having a genetic test for susceptibility to major depression, if it was available. Having a family history of mental illness was cited as a major reason. After discussion of perceived positive and negative implications of predictive genetic testing, nine of 24 participants initially interested in having such a test changed their mind. Fear of genetic discrimination and privacy issues predominantly influenced change of attitude. All participants still interested in having a predictive genetic test for risk for depression reported they would only do so through trusted medical professionals. Participants were unanimously against direct-to-consumer genetic testing marketed through the Internet, although some would consider it if there was suitable protection against discrimination. The study highlights the importance of general practitioner and public education about psychiatric genetics, and the availability of appropriate treatment and support services prior to implementation of future predictive genetic testing services.

Community interest in predictive genetic testing for susceptibility to major depressive disorder in a large national sample

BACKGROUND Despite international concern about unregulated predictive genetic testing, there are surprisingly few data on both the determinants of community interest in such testing and its psychosocial impact. METHOD A large population-based public survey with community-dwelling adults (n=1046) ascertained through random digit dialling. Attitudes were assessed by structured interviews. RESULTS The study found strong interest in predictive genetic testing for a reported susceptibility to depression. Once the benefits and disadvantages of such testing had been considered, there was significantly greater interest in seeking such a test through a doctor (63%) compared to direct-to-consumer (DTC; 40%) (p<0.001). Personal history of mental illness [odds ratio (OR) 2.58, p<0.001], self-estimation of being at higher than average risk for depression (OR 1.92, p<0.001), belief that a genetic component would increase rather than decrease stigma (OR 1.62, p<0.001), and endorsement of benefits of genetic testing (OR 3.47, p<0.001) significantly predicted interest in having such a test. CONCLUSIONS Despite finding attitudes that genetic links to mental illness would increase rather than decrease stigma, we found strong community acceptance of depression risk genotyping, even though a predisposition to depression may only manifest upon exposure to stressful life events. Our results suggest that there will be a strong demand for predictive genetic testing.

Review of the quality of information on bipolar disorder on the Internet

Objectives: The aim of the present study was to assess the quality of commonly found websites on bipolar disorder. A specifically designed quality tool, the Bipolar Website Quality Checklist (BWQC), was developed for this purpose. Methods: The BWQC was developed from quality criteria identified by a literature review of Medline (1966 +), Medline in-process and non-indexed citations, PsychINFO, CINAHL, EMBASE, Pub Med, Science citation index, and Psych Articles, using keywords: ‘quality, reliability, accuracy, readability, evaluation, assessment, information, internet, web, www’. To identify relevant websites, seven common search engines were accessed and searched using a string of key words: ‘bipolar disorder + mania+ manic depression+ hypomania’. The top active 15 sites identified were rated by three independent raters, using the BWQC and DISCERN instruments. Results: There was a wide variability in the quality of the websites reviewed. The Black Dog Institute website was ranked first by the BWQC and DISCERN instruments. The National Institute of Mental Health website was ranked second by DISCERN and seventh by BWQC. The BWQC demonstrated high interrater reliability (r = 0.89) and correlated strongly (r = 0.78, p = 0.001) with the more generic DISCERN instrument. Websites with an editorial board or affiliation to a professional organization or which contained information on a variety of mental health issues had higher quality information on bipolar disorder and its treatment than websites that did not share these characteristics. Conclusions: High-quality information on bipolar disorder does exist on the Internet. It is important that clinicians are familiar with such websites so that they can recommend the most appropriate site that meets the specific need of the individual. Use of such websites can assist clinicians in adhering to clinical practice guidelines by providing material to augment psychoeducational interventions.

A meta-analysis of the risk of major affective disorder in relatives of individuals affected by major depressive disorder or bipolar disorder

BACKGROUND To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated. METHODS A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods. RESULTS Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72-2.67), increasing to OR=3.23 (95% CI 2.11-4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45-25.61), and OR=6.58 (95% CI 2.64-16.43) for FDRs of two BD probands. CONCLUSIONS These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates.

Predictive and Diagnostic Genetic Testing in Psychiatry

The recent advent of commercially available genetic tests for the diagnosis of several mental illnesses has led to intense controversy amongst the psychiatric research community. In this article the authors review these developments, and contrast these with the growing evidence from genomewide association studies that highly heritable psychiatric conditions such as schizophrenia are due to the contributions and interaction of multiple allelic variants, each of small effect size. There is also evidence for the contribution of some highly penetrant rare de novo copy number variants, though the lack of disease specificity for these is of concern. This article outlines the prerequisites for predictive and diagnostic genetic tests, such as clinical validity and utility, and reviews the opportunity that genetic tests for mental illnesses present. As the scientific discourse on genetic tests for complex disorders is not limited to psychiatry, the authors outline current thoughts on the significance of genome-wide association studies across health, and the phenomenon of direct-to-consumer tests in medicine. The attitudes and understanding of patients, families, and clinicians about the future (currently hypothetical) scenario of psychiatric genetic tests are discussed, as is the potential for such testing to increase, rather than diminish stigma. Finally, recommendations on the future development and availability of genetic tests in psychiatry are provided.

IMPLICATIONS OF THE USE OF GENETIC TESTS IN PSYCHIATRY, WITH A FOCUS ON MAJOR DEPRESSIVE DISORDER: A REVIEW

Advances in technology have enabled research to link many genetic markers to specific disease risk. This has led to the commercialization of genetic tests across a wide range of medical disorders. Public interest in ones own future health and an increasing desire for autonomy over ones health care have facilitated a large and growing market for such genetic tests to be sold direct to the consumer (DTC). Amidst a plethora of tests for a broad range of medical conditions, DTC genetic tests currently include a number of tests related to risk for various psychiatric illnesses including major depressive disorder (MDD), bipolar disorder, schizophrenia, and obsessive‐compulsive disorder and also for prediction of individual response to psychotropic medication. Although a large number of studies show that there is strong public interest in genetic susceptibility testing for psychiatric disorders, little is known about the impact on individuals of receiving the results of genetic tests. Moreover, the low predictive power and uncertain clinical validity and utility of DTC genetic tests for psychiatric disorders have led to both controversy and difficulties of interpretation of results. This review summarizes the rationale for using genetic risk tests in psychiatry, as an intervention for protective cognitive and behavioral change, and to predict medication response, with a focus on MDD. Since genetic risk information has the potential to influence major life‐changing health decisions, there is an imperative to ensure that there is an appropriate evidence base to support the use of such genetic tests.

Community attitudes towards mental health interventions for healthy people on the basis of genetic susceptibility

Objectives: The aim of the present study was to evaluate, using serotonin transporter genotyping as an example, the preparedness of individuals from an urban general population identified with hypothetical genetic risk for a depressive disorder to moderate risk through cognitive or behavioural intervention. It also evaluated endorsement of genetic and environmental causal attributions of mental illness. Method: A qualitative approach using focus group methodology was selected as most appropriate because these issues are relatively unexplored. Participants (n=36) aged ≥18 years from metropolitan Sydney discussed their understanding of the role of genetic and environmental risk factors in mental illness and attitudes towards pre-symptomatic interventions based on genetic risk information. Results: Thirty-six participants attended four focus groups involving 8-10 participants per group. Participants predominantly viewed genetic risk factors for depression as predisposing rather than causal, with environmental risk factors acting as triggers. Hypothetical identification with a genetic variant suggesting predisposition to depression prompted strong interest in seeking further information about predictive genetic testing from medical professionals, willingness to reduce life stress, drugs and alcohol intake, willingness to increase exercise, and willingness to undertake cognitive and behavioural interventions at a pre-symptomatic stage. Mixed views prevailed as to whether stress was a modifiable risk factor. Preventive intervention at a presymptomatic stage of depression was viewed negatively in a minority of participants due to a fatalistic attitude towards a genetic predisposition and attitudes that intervention was futile in the absence of symptoms. Conclusions: There is a likely public demand for preventive mental health interventions for healthy people on the basis of genetic susceptibility if predictive genetic testing becomes available in psychiatry. The findings have implications for general practitioner and public education about predictive genetic testing for susceptibility to common multifactorial disorders for at-risk groups.

Attitudes of medical genetics practitioners and psychiatrists toward communicating with patients about genetic risk for psychiatric disorders.

Objectives The aim of this study was to examine the self-rated competencies and perceived roles of medical geneticists, genetic counselors, and psychiatrists in the communication of genetic risk for psychiatric disorders to patients and families at an increased risk for schizophrenia, bipolar disorder or major depressive disorder, and their perspectives on training needs in this field. Materials and methods Clinically active members of the Human Genetics Society of Australasia (HGSA) and the Royal Australian and New Zealand College of Psychiatrists (RANZCP) were invited to complete the online survey. A total of 157 responses were included in data analysis: 17 medical geneticists, 36 genetics counselors, and 104 psychiatrists. Results In all, 34.4% of the respondents disagreed that their professional training had prepared them to discuss genetic information about psychiatric illnesses with patients. Medical geneticists perceived significantly higher levels of self-rated competency to discuss with patients and families genetic information on psychiatric disorders compared with genetic counselors and psychiatrists (t=−0.61, P=0.001; &bgr;=0.33, 95% confidence interval 0.16–0.49, P<0.001). Conclusion Findings suggest deficiencies in education and training programs on how to best communicate psychiatric genetic risk information to patients, suggesting that specialist programs are needed to better support health professionals. As self-rated competencies differed among the professional groups, training programs need to be tailored to participants’ professional backgrounds.

Portrayal of psychiatric genetics in Australian print news media, 1996-2009

Objective: To investigate how Australian print news media portray psychiatric genetics.

Exploring Culture-Specific Differences in Beliefs about Causes, Kinship and the Heritability of Major Depressive Disorder: The Views of Anglo-Celtic and Chinese-Australians

The aim of this study was to explore cultural differences in causal attributions and beliefs about heritability of major depressive disorder (MDD). Face-to-face interviews with Anglo-Celtic- and Chinese-Australians community members with a family history of MDD were conducted and subjected to a rigorous qualitative analysis, using the computer software NVivo. Sixteen Anglo-Celtic-Australians and 16 Chinese-Australians were interviewed. Both groups believed that a combination of genetic and environmental factors contributed to MDD, that stress was an important cause of MDD, and that coping factors were significant moderators of the impact of stress on MDD. Both cultural groups believed that the causes of MDD affecting multiple family members included a shared family environment and a “contagion effect”, in addition to genetics. Unique to the Chinese-Australian group was the beliefs that parental pressures to exceed academically contributed to MDD; this cultural group also reported beliefs that depression was due to God’s will or alternatively fate, which in turn was related to attributions to feng shui and auspicious dates. This study documented key culture-specific differences in beliefs about causes and inheritance of MDD; such differences have major implications for clinician-patient communication about genetic risk associated with having a family history of MDD.