The borderline diagnosis II: Biology, genetics, and clinical course

Andrew E. Skodol, Larry J. Siever, W. John Livesley, John G. Gunderson, Bruce Pfohl, Thomas A. Widiger

Research output: Contribution to journalReview articlepeer-review

316 Scopus citations


In Part I of this three-part article, consideration of the core features of BPD psychopathology, of comorbidity with Axis I disorders, and of underlying personality trait structure suggested that the borderline diagnosis might be productively studied from the perspective of dimensions of trait expression, in addition to that of the category itself. In Part II, we review the biology, genetics, and clinical course of borderline personality disorder (BPD), continuing to attend to the utility of a focus on fundamental dimensions of psychopathology. Biological approaches to the study of personality can identify individual differences with both genetic and environmental influences. The aspects of personality disorder that are likely to have biologic correlates are those involving regulation of affects, impulse/action patterns, cognitive organization and anxiety/inhibition. For BPD, key psychobiological domains include impulsive aggression, associated with reduced serotonergic activity in the brain, and affective instability, associated with increased responsivity of cholinergic systems. There may be a strong genetic component for the development of BPD, but it seems clear, at least, that there are strong genetic influences on traits that underlie it, such as neuroticism, impulsivity, anxiousness, affective lability, and insecure attachment. The course of BPD suggests a heterogenous disorder. Predictors of poor prognosis include history of childhood sexual abuse, early age at first psychiatric contact, chronicity of symptoms, affective instability, aggression, substance abuse, and increased comorbidity. For research purposes, at least, biological, genetic, and prognostic studies all continue to suggest the need to supplement categorical diagnoses of BPD with assessments of key underlying personality trait dimensions and with historical and clinical observations apart from those needed to make the borderline diagnosis itself.

Original languageEnglish
Pages (from-to)951-963
Number of pages13
JournalBiological Psychiatry
Issue number12
StatePublished - Jun 15 2002

Bibliographical note

Funding Information:
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.

Funding Information:
Supported in part by the Borderline Personality Disorder Research Foundation and NIMH grant MH 50839.


  • Affective instability
  • Borderline
  • Course
  • Genetics
  • Impulsive aggression
  • Personality disorder

ASJC Scopus subject areas

  • Biological Psychiatry


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