The prevailing view among many psy­chiatrists and mental health profession­als is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behav­ioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modali­ties, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neuro­biological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.

No wonder that 42 published stud­ies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnor­malities in brain structure and function.1 These anomalous patterns have been detected across all 4 available neuroim­aging techniques.

Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD: • hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex • variations in the CA1 region of the hippocampus and subiculum • smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%) • larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus • loss of gray matter in the frontal, temporal, and parietal cortices • an enlarged third cerebral ventricle • in women, reduced size of the me­dial temporal lobe and amygdala • in men, a decreased concentra­tion of gray matter in the anterior cingulate • reversal of normal right-greater-than-left asymmetry of the orbitofron­tal cortex gray matter, reflecting loss of gray matter on the right side • a lower concentration of gray mat­ter in the rostral/subgenual anterior cin­gulate cortex • a smaller frontal lobe.

In an analysis of MRI studies,2 cor­relation was found between structural brain abnormalities and specific symp­toms of BPD, such as impulsivity, sui­cidality, and aggression. These findings might someday guide personalized in­terventions—for example, using neuro­stimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).

Magnetic resonance spectroscopy. In BPD, MRS studies reveal: • compared with controls, a higher glutamate level in the anterior cingulate cortex • reduced levels of N-acetyl aspar­tate (NAA; found in neurons) and cre­atinine in the left amygdala • a reduction (on average, 19%) in the NAA concentration in the dorsolat­eral prefrontal cortex.

Functional magnetic resonance im­aging. From fMRI studies, there is evi­dence in BPD of: • greater activation of the amygdala and prolonged return to baseline • increased functional connectiv­ity in the left frontopolar cortex and left insula • decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes • marked frontal hypometabolism • hypermetabolism in the motor cor­tex, medial and anterior cingulate, and occipital and temporal poles • lower connectivity between the amygdala during a neutral stimulus • higher connectivity between the amygdala during fear stimulus • higher connectivity between the amygdala during fear stimulus • deactivation of the opioid system in the left nucleus accumbens, hypothal­amus, and hippocampus • hyperactivation of the left medial prefrontal cortex during social exclusion • more mistakes made in differenti­ating an emotional and a neutral facial expression.

Diffusion tensor imaging. DTI white-matter integrity studies of BPD show: • a bilateral decrease in fractional an­isotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi • a decrease in FA in the genu and rostrum of the corpus callosum • a decrease in inter-hemispheric connectivity between right and left ante­rior cigulate cortices.

Genetic StudiesThere is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).

A systematic review of the heritabil­ity of BPD examined 59 published stud­ies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment inter­action studies.3 The authors concluded that BPD has a strong genetic compo­nent, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).