ReviewThe borderline diagnosis III: identifying endophenotypes for genetic studies
Introduction
Although there is general consensus that borderline personality disorder (BPD) has a multifactorial etiology including both genetic and environmental influences, there has been little systematic research into the specific genetic and environmental antecedents to this disorder. In part, the interpersonal and psychodynamic considerations that provided the original impetus to define this disorder and address its treatments may not lend themselves as easily to classic genetic approaches as more simply defined disorders; however, if the BPD diagnosis is reframed in terms of more specific, measurable, presumably biologically based endophenotypes, the possibilities of identification of genetic predisposing factors might be considerably improved. Such a reframing that might generate fruitful genetic investigation into this disorder might then encourage more rigorous research, attracting investigators to what has heretofore been seen as a somewhat “fuzzy” diagnosis from a genetic point of view. A better understanding of the genetics of this disorder might improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities.
Section snippets
Family aggregation studies of BPD
Currently there is substantial evidence for familial aggregation of BPD or traits as a greater frequency of the diagnosis of BPD or borderline traits are seen in the relatives of probands with BPD than in comparison groups Baron et al 1985, Links et al 1998, Loranger et al 1982, Pope et al 1983, Reich 1989, Silverman et al 1991, Soloff and Millward 1983, Torgersen 2000, Zanarini et al 1988. The frequency of BPD features among first-degree relatives of BPD probands varies from study to study,
Heritability of personality disorder
A number of studies have examined heritability of different facets of personality, although most have not focused on the personality disorder diagnoses. Studies of twins reared together and apart suggest a strong genetic influence on personality dimensions such as neuroticism and extraversion Pedersen et al 1991, Tellegen et al 1988. Adoption studies of samples with diagnosed personality disorders have demonstrated a genetic influence on the development of antisocial personality disorder
Strategies for genetic studies of BPD
Ideally, the most definitive study would identify a large number of twins in an epidemiologic nonclinically ascertained sample but with a sufficient prevalence of probands with the diagnoses of BPD to achieve substantial power for genetic studies. The twins could then be systematically identified and recruited for the study. In this kind of study, subjects would be evaluated with regard to clinical phenotype by diagnostic interview, self-report measures of personality traits, and laboratory
Endophenotypic/dimensional approaches
If BPD is conceptualized as a personality disorder emerging from the interaction of underlying genetically based traits Siever and Davis 1991, Livesley et al 1992, the prospect for identifying underlying endophenotypes becomes potentially more feasible. Endophenotypes represent measurable characteristics that reflect an underlying genotype that may be more closely related to that genotype than the diagnostic category itself. The endophenotype approach is being successfully applied to the
Acknowledgements
This paper was commissioned by and written with the support of the Board of Trustees of the Borderline Personality Disorder Research Foundation (BPDRF) and aspects of this work were presented and discussed at the First Annual Scientific Meeting of the Foundation, July 13–14, 2000. The authors are or were members of or consultants to the Scientific Advisory Board of the BPDRF. The authors appreciate the helpful comments of Steven Hyman, M.D.
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