Imaging Technique Reveals Clues to Borderline Disorder Symptoms

Could an overly charged executive control center explain the impulsivity of borderline personality disorder (BPD)? A new study suggests that this might be the case.

The lead investigator was Mareen Hoerst, Dr.sc., of the Central Institute of Mental Health in Mannheim, Germany. The study was published July 5 in the online version of the Archives of General Psychiatry.

Thanks to a technique called proton magnetic resonance spectroscopy (MRS), scientists can now visualize neurotransmitters in the brain. Some previous researchers used the technique to demonstrate significantly higher levels of the excitatory neurotransmitter glutamate in the anterior cingulate cortex—the brain's executive control center—of subjects with BPD than in the anterior cingulate cortex of healthy control subjects. This finding suggested that abnormally elevated levels of glutamate within the anterior cingulate cortex might play a role in BPD.

But the BPD subjects in this particular study also had attention-deficit/hyperactivity disorder (ADHD), thus throwing a putative link between the high glutamate levels and BPD into question. Hoerst and her colleagues decided that they would try to replicate the findings in BPD subjects who did not have ADHD.

They used MRS to measure levels of glutamate within the anterior cingulate cortex of 30 subjects meeting DSM-IV criteria for BPD and in 30 healthy age- and gender-matched controls. They then compared glutamate levels in the two groups.

Glutamate levels were significantly higher in the BPD subjects than in the control ones, they found. Subgrouping BPD subjects for current posttraumatic stress disorder (PTSD) (n=11), lifetime PTSD (n=13), and lifetime depression (n=18) did not yield significant differences between subgroups. (Some subjects had depression comorbid with PTSD.)

These findings thus confirmed what the other study had suggested—that abnormally high levels of glutamate are implicated in BPD.

Moreover, Hoerst and her team found a significant link between glutamate concentrations in the anterior cingulate cortex of their BPD subjects and these subjects' scores on the Barratt Impulsiveness Scale. In other words, the more glutamate in the brain, the more impulsive behaviors may appear.

This finding, coupled with the others, implied that excess glutamate in the anterior cingulate cortex might contribute to the impulsivity characteristic of BPD.

The findings may also have clinical implications, the researchers suggested. For example, individuals with BPD are known to be at heightened risk of suicide, presumably because of their impulsive tendencies. If excess glutamate in the anterior cingulate cortex contributes to impulsivity in BPD, then giving individuals with BPD glutamate antagonists might help prevent them from engaging in suicidal behaviors. Some preliminary evidence that glutamate antagonists can achieve such a goal was reported by John Krystal, M.D., chair of psychiatry at Yale University, in the November 2005 Journal of Clinical Psychiatry.

The findings from this study are also interesting because heightened cortical glutamate levels have been linked with major depression, Krystal told Psychiatric News. “In some regions of the brain, these elevated glutamate levels normalize during effective antidepressant medication treatments, raising the possibility that the normalization of elevated cortical glutamate levels might also be an objective in the pharmacologic treatments for BPD.”

The study was funded by the German Research Foundation.

An abstract of “Correlation of Glutamate Levels in the Anterior Cingulate Cortex With Self-Reported Impulsivity in Patients With Borderline Personality Disorder and Healthy Controls” is posted at <http://archpsyc.ama-assn.org/cgi/content/short/2010.93>.