The Neurobiology of Borderline Personality Disorder
The Neurobiology of Borderline Personality Disorder
Clarification of the molecular and biological underpinnings of borderline personality disorder (BPD) is imperative for a more thorough understanding of the disorder, one that anchors our quest for effective treatment. This article provides a brief overview of the neurobiology of BPD. Anatomical structures are reviewed as well as genetic and epigenetic factors that contribute to the pathophysiology and, potentially, to the treatment of this disorder.
Neuroanatomy and imaging
Over the past decade, much of the literature concerning the biological basis of BPD has shifted to direct visualization of brain structure and function using neuroimaging. Most of the findings pertain to brain regions involved in emotional processing, such as the amygdala, insula, posterior cingulate cortex, hippocampus, anterior cingulate cortex, and prefrontal regulatory regions (Figure 1). These include the orbital frontal cortex, dorsal lateral prefrontal cortex, and ventral lateral prefrontal cortex.
Volume. A meta-analysis of brain volume—which comprised 281 persons with BPD and 293 healthy controls—and 19 imaging studies noted left amygdala and right hippocampus gray volume decreases in persons with BPD.1 Volume studies in adolescent-onset BPD populations also exist but are limited by small sample size, discrepant imaging techniques, and highly comorbid presentations. They do not reproduce the volume differences reported in studies of adult BPD.2
Function. A meta-analysis of functional MRI (fMRI) findings in persons with BPD revealed heightened activation during processing of negative emotional stimuli in the left amygdala, left hippocampus, and posterior cingulate cortex as well as diminished activation in prefrontal regions (including the dorsal lateral prefrontal cortex).3 Another meta-analysis showed heightened activity in the insula and less activation in the subgenual anterior cingulate cortex in persons with BPD but did not find amygdala hyperactivity.1
Conflicting amygdala results are believed to result from the medication status of research participants because psychoactive drugs attenuate limbic activity. Pharmacologic probes have also shown decreased metabolic activity in the anterior cingulate cortex and orbital frontal cortex in response to serotonergic challenge in impulsive-aggressive and affectively unstable BPD populations, and decreased coupling of resting metabolism between the orbital frontal cortex and the ventral anterior cingulate cortex has been reported.4
Dialectical behavioral therapy (DBT) was found to attenuate amygdala hyperactivity at baseline, which correlated with changes in a measure of emotion regulation and increased use of emotion regulation strategies.5 Taken together, these findings highlight that dysfunctional circuits involving hyperactive limbic regions and hypoactive prefrontal modulation—most pronounced in the dorsal lateral prefrontal cortex—represent the anatomical corollaries to BPD.
Connectivity. Connectivity studies developed over the past 2 years introduced novel research strategies that heavily rely on fMRI. Connectivity can be described in terms of anatomical and functional connectivity. Diffusion tensor variables of mean diffusivity and fractional anisotropy are measures of white matter integrity and anatomical connections. While such work in BPD is in its infancy, initial data suggest that deficits in frontolimbic connections relate to the severity of symptoms such as affective instability, avoidance of abandonment, and anger.6
Functional connectivity analyses provide information about which brain regions are co-activated and can be studied using seed-based correlations (most often with the amygdala and dorsal anterior cingulate cortex) and independent component analysis. The 3 networks most salient in BPD are:
• The default mode: a network activated when the brain is at rest in the absence of goal-directed activity; it is influenced by the medial prefrontal cortex and posterior cingulate cortex and is responsible for self-referential thinking
• The salience network, including the orbital frontal insula and the dorsal anterior cingulate cortex
• The medial temporal lobe network, which is responsible for processing negative emotions
In BPD, there are alterations in the connections between these 3 networks with particularly problematic connectivity between salience detection and self-referential encoding. This results in misidentification with neutral stimuli as well as a failure to integrate salience information with internal representations.
These networks can be mapped on fMRI, which shows dampening of the negative correlations between the dorsal anterior cingulate cortex and the posterior cingulate cortex as well as increased connectivity of the amygdala and rostral anterior cingulate cortex. Connectivity is also heightened between the amygdala and parahippocampus as well as the ventral anterior cingulate cortex and insula. In a study that examined neural correlates of emotional distraction, persons with BPD showed positive connectivity between the amygdala and prefrontal regions (right default mode prefrontal cortex and left dorsolateral prefrontal cortex).6