The borderline diagnosis III: identifying endophenotypes for genetic studies

Although it is generally acknowledged that borderline personality disorder (BPD) has a complex, multifactorial etiology with interacting genetic and environmental substrates, the specific genetic underpinnings of this disorder have not been extensively investigated. Family aggregation studies suggest the heritability for BPD as a diagnosis, but the genetic basis for this disorder may be stronger for dimensions such as impulsivity/aggression and affective instability than for the diagnostic criteria itself. Family, adoptive, and twin studies also converge to support an underlying genetic component to the disorder. An endophenotypic approach to defining the genetics of this complex disorder may be called for. Twin studies in an epidemiologic, non-clinically ascertained sample using both diagnostic measures and laboratory measures that can be operationalized, including neuropsychologic, psychophysiologic, and operationalized behavioral tests, may be useful. Large-scale family studies of clinically ascertained samples with careful diagnostic demarcation and measurement of endophenotypes in probands and relatives may also prove to be a promising approach. The use of laboratory paradigms for measures of aggression and affective instability are discussed in the context of such endophenotypic approaches.