Volumetrics and spectroscopy

Neuroimaging research in the field of BPD began in the early 1980s with the use of computed tomography (CT). Similar to research on brain alterations in schizophrenic patients, whole brain volumes and ventricle sizes were investigated. In contrast to findings in schizophrenia, studies in BPD did not show ventricular enlargement (Schulz et al., 1983; Snyder et al., 1983), or changes in ventricle–brain ratio (Lucas et al., 1989) in patients with BPD. With the advent of Magnetic Resonance Imaging, Lyoo reported a marginally significant reduction of overall frontal lobe volumes in BPD (Lyoo, 1998), although this finding has been criticized for technical reasons such as low spatial resolution and lack of correction for head tilt.

BPD has been suggested to be part of a trauma-related psychiatric spectrum of psychiatric disorders (Bremner, 2002), with posttraumatic stress disorder (PTSD) as the core of the spectrum, but also including BPD, depression and dissociative disorders. A major neurobiological finding of the last decade is a reduction in hippocampal volume as assessed by MR-based volumetry in combat-related (Bremner et al., 1995; Gilbertson et al., 2002; Gurvits et al., 1996) as well as abuse-related PTSD (Bremner et al., 1997; Bremner et al., 2003; Stein et al., 1997). There is an ongoing debate as to whether this volume reduction is due to an elevated activity of stress-associated neurobiological systems, such as the HPA axis or is genetically determined (Gilbertson et al., 2002). In contrast to the finding of reduced hippocampal volume, all published studies investigating amygdala volumes in patients with PTSD did not find any significant amygdala volume difference compared to controls (Bonne et al., 2001; Bremner et al., 1997; De Bellis et al., 1999; Gilbertson et al., 2002; Gurvits et al., 1996).

The first investigation of MRI-based volume of hippocampus and amygdala (Driessen et al., 2000) found 16% smaller volumes of the hippocampus and 8% smaller volumes of the amygdala in women with BPD compared to healthy controls. Tebartz van Elst et al. (2003) found an even more pronounced volume difference between patients with BPD and controls with 20.5% smaller hippocampal and 24% smaller amygdala volume. In addition, they found a highly significant volume-reduction of the left orbitofrontal cortex and of the right anterior cingulate cortex. Our own investigation revealed a reduction of 13% for hippocampus and 21% for amygdala (Schmahl et al., 2003a). A fourth study (Brambilla et al., 2004) also found volume reduction of hippocampus and amygdala, however these reductions did not reach significance. The authors also explored structural brain changes in BPD in relation to childhood abuse. Compared to 20 healthy controls, the ten unmedicated (abuse: n = 6, no abuse: n = 4) BPD patients, male and female, had significantly smaller right and left hippocampal volumes and significantly increased right and left putamen volumes. There were still significant differences in hippocampal volume when BPD patients with history of childhood abuse were compared to healthy controls. This significance disappeared when comparing healthy controls to BPD patients without childhood abuse. No significant differences between groups were found for caudate, amygdala, temporal lobes, dorsolateral prefrontal cortex and total brain volumes. The authors conclude that early traumatic experiences may play a role in hippocampal atrophy.

Taken together, these findings suggest that, in contrast to PTSD, not only hippocampus but also amygdala volumes seem to be reduced in patients with BPD. In a study using voxel-based morphometry, grey matter volume loss was found in the left amygdala without differences in grey or white matter volume or density anywhere else in the brain (Ruesch et al., 2003).

A different approach to assess neuronal dysfunction is Magnetic Resonance Spectroscopy, which measures concentration of neurochemical metabolites such as N -acetylaspartate (NAA), choline, or lactate in specified brain regions. Tebartz van Elst et al. (2001) found a significant 19% reduction of NAA concentration in the dorsolateral prefrontal cortex in patients with BPD compared to controls, suggesting neuropathology in this area of the brain. More studies are needed in this area to draw definite conclusions about disturbed brain metabolism in BPD.

Go to: