Interest, rationale, and potential clinical applications of genetic testing for mood disorders: A survey of stakeholders

Bipolar disorder (BP) and major depressive disorder (MDD) are among the most severe, persistent, and debilitating illnesses occurring in young people, with an estimated lifetime prevalence of approximately 1-1.5% for BP (Kessler et al., 2005; Kato, 2007; Merikangas et al. 2007; Braff and Freedman, 2008) and 9.2–19.6% for MDD (Kessler et al., 2005; Vicente et al. 2006; Kao et al. 2011). Although genetic testing for psychiatric disorders has been the goal of psychiatrists and geneticists for years (Braff and Freedman, 2008) this goal has been difficult to attain since the impact of individual genes on risk for psychiatric illness is small, often nonspecific and embedded in intricate causal pathways (Kendler, 2005). In contrast to Mendelian disorders, tests for complex conditions such as MDD and BP may yield only weak estimates of risk, as such conditions appear to be caused by a complicated interplay of multiple genetic and environmental factors, and the associated genetic variants may be common and confer only a small increment of increased or decreased risk (Wright and Kroese, 2010). Major depressive disorder and BP clearly have an important genetic component (Trippitelli et al. 1998; Bienvenu et al., 2010), yet results from genetic testing research have been largely confusing and contradictory (Jordan and Tsai, 2010). However, recent progress in the identification of millions of genetic markers and in powerful detection technologies has made it feasible to perform large-scale association analyses that have enough statistical power to identify genes exerting a relatively minor effect on the likelihood of a particular ailment (Bienvenu et al., 2010; Jordan and Tsai, 2010). In the current DNA-centered mindset, genetic tests are often seen as the first step towards new therapies, and many patient groups are lobbying for their development in the belief that such testing can be helpful in selecting the best treatment (as may occasionally be the case) or in reassuring anxious parents (Jordan and Tsai, 2010). Companies involved in molecular diagnostics, a $20 billion market in the United States, strive to develop diagnostic kits and systems, (Jordan and Tsai, 2010). Tests claiming to indicate increased genetic risks for BP and antidepressant response are already available commercially from companies, such as 23andMe. Great hopes are attached to psychiatric genetics with the goal of both better treatment and prevention and the anticipated de-stigmatizing effect of attributing mental illness to biological causes (Smits et al., 2007; Braff and Freedman, 2008; Couzin, 2008; Laegsgaard et al., 2009; Hoop et al., 2010; Facio et al., 2011). For carriers of variants that influence risk, genetic testing provides the potential to improve outcomes through prevention, early detection, tailored medication, and a better-quality basis for making reproductive decisions (Meiser et al., 2008). Studies have found positive attitudes towards predictive genetic testing for predisposition to psychiatric disorders among various stakeholders. These stakeholders have included: people with an unspecified psychiatric diagnosis (Laegsgaard and Mors, 2008), individuals affected by BP (Trippitelli et al., 1998; Laegsgaard et al., 2009) or MDD (Laegsgaard et al., 2009), people with multiple relatives affected by BP (Jones et al., 2002; Meiser et al., 2005, 2008), psychiatrists (Jones et al., 2002; Hoop et al., 2010), psychology students (Laegsgaard and Mors, 2008), and the general public (Wilde et al., 2010). This interest in psychiatric genetic testing seems to remain even without available preventative treatment options (Laegsgaard and Mors, 2008, 2009) and even if results offer only a probabilistic rather than definitive risk (Wilde et al., 2010). In spite of the positive attitudes toward genetic testing for mood disorders demonstrated by these studies, key related topics have not been explored in depth. There is limited research examining: specific reasons why individuals are interested in genetic tests for mood disorders (Trippitelli et al., 1998; Mesier et al., 2008; Wilhelm et al., 2009), how the level of test predictability affects interest in genetic testing for mood disorders, and the preferred manner to receive genetic test results for mood disorders (Wilde et al., 2010; Borry et al., 2010). This study explored these issues with individuals with a personal and/or family history of mood disorders as well as individuals with no personal or family history of mood disorders. The study examined potential reasons why stakeholders might be interested in genetic testing for risk of mood disorders, how predictive value affects level of interest in testing and preferences for the best manner to receive test results. It also hopes to add further insights to the ongoing debate about the potential impact of genetic attribution on the stigma associated with mental illness (Mechanic et al., 1994; Meiser et al., 2007; Laegsgaard and Mors, 2008; Meiser et al., 2008; Wilde et al., 2010).