Neurobiology of Borderline Personality Disorder

The principle dimensions that have been the focus of biological research include impulsive aggression and affective instability

Impulsive Aggression

  • Issues with impulse control
  • Decrease central serotonergic activity (associated with increase impulsive aggression)
  • Diminished concentrations of serotonin in 5-HIAA in the CSF has been associated with attempted or completed suicides
  • Fenfluramine (drug to increase serotonin activity) creates a Blunted prolactin response (hormone produced in pituitary gland) in individuals diagnosed with BPD. These findings indicate an associate between blunted serotonergic responsiveness and impulsive aggression.


Family and twin  studies of borderline personality disorder suggest that while the disorder itself may not be heritable, the prominent features of impulsivity appears to run in family.

In an ongoing study of the health and lifestyles of families with twins in the Netherlands, Trull and colleagues examined 711 pairs of siblings and 561 parents to identify the location of genetic traits that influences the manifestation of BPD. The researchers conducted a genetic linkage analysis of the families and identified chromosomal regions that could contain genes that influence the development of BPD. Trull found the strongest evidence for a genetic influence on BPD features on chromosome nine.


  • Prefrontal cortex, particularly prefrontal orbital cortex and adjacent ventral medial cortex, appears to play a role in aggressive behavior.
  • Phineas Gage example
  • Results of PET studies on patients meeting criteria for BPD showed decreased metabolism in prefrontal cortex, particularly orbital and adjacent ventral medial frontal cortex, associated with increased impulsive aggressive behavior.

Affective Instability

  • Defined as “a predisposition to marked, rapidly reversible shifts in affective states that are extremely sensitive to meaningful environmental events”
  • Basically Emotional Dysregulation – which is a defining characteristic of BPD


  • Cholinergic system plays a role in regulating affect
  • Research shows that cholinergic agents appear to induce depressed mooed in normal patients and patients with depression, this effect appears even more intense in those with BPD
  • There is also evidence of disturbance in noradrenergic activity in effectively unstable patients with BPD
  • More research is needed.