(BPD) is a serious, chronic illness associated with aggressive behavior, suicidality, and high risk, all of which are known to decrease quality of life (Doerfler et al. 2010
). Onset of BPD in childhood tends to be more severe and complicated than BPD of adult onset (Carter et al. 2004
; Perlis et al. 2004
). The National Institute of Mental Health's Systematic Treatment Enhancement Program for BPD study included 983 subjects (Perlis et al. 2004
). Of those subjects in whom the age of onset of mood symptoms could be determined, 27.7% had age of onset before age 13. Early onset was associated with higher rates of co-morbid anxiety disorders and substance abuse, more recurrences, shorter periods of euthymia, and a greater likelihood of suicide attempts and violence (Perlis et al. 2004
The neural basis of BPD is not well understood. In recent years, it has been recognized that white matter (WM) makes an important contribution to cognition and emotion. WM comprises nearly half the brain volume and plays a key role in development, aging, and many neurological and psychiatric disorders across the life span (Filley 2005
). Thus, investigating WM may elucidate our understanding of psychopathology in BPD.
Diffusion tensor imaging (DTI) provides information about WM microstructure in vivo
(Basser et al. 1994
; Huppi et al. 2001
), and permits the study of connections among anatomically and functionally defined brain regions (Conturo et al. 1999
). Myelin sheaths and cell membranes restrict the diffusion of water perpendicular to the direction of the axons in WM, whereas water diffuses relatively freely parallel to the axons. This directional dependence of diffusion is often quantified as anisotropy, which reflects myelination of axons and the coherence of axonal orientation (Neil et al. 1998
). Fractional anisotropy (FA) is a unit-less and normalized measure of diffusion anisotropy (ranging from 0 to 1) that provides information about the degree of fiber organization and integrity. Mean diffusivity that characterizes the size of the measured diffusion tensor has also been used to detect WM abnormality. Diminished anisotropy of water diffusion and increased apparent diffusion coefficient (ADC) has been proposed to reflect compromised WM integrity (i.e., a disruption or disorganization of tracts) (Beaulieu 2002
). WM has an extremely high level of structural organization that compartmentalizes and restricts water motion; thus, DTI, which is inherently sensitive to water diffusivity, has great potential for investigating WM contributions to psychopathology, including BPD.
A recent review suggested that the corpus callosum (CC) may play a role in the pathogenesis of BPD (Bellani et al. 2009
). The CC is involved in integrating sensory-motor functions, attention, language, and memory-executive functions frequently compromised in BPD. The CC is, by far, the largest WM structure in the human brain, and the midsagittal CC can be further partitioned into segments connecting different parts of the two cerebral hemispheres () (Huang et al. 2005
). Few detailed analyses at the multiple segments of the CC have been conducted for children and adolescents with BPD, which is somewhat surprising given that investigating these segments may reveal which brain areas are affected by the CC disruption. For example, the genu connects the prefrontal and orbital areas, and the splenium of CC connects the occipital areas. DTI studies of the CC in children and adolescents with BPD report lower FA values in the genu and body (Frazier et al. 2007
), higher ADC and reduced fiber coherence in the splenium (Pavuluri et al. 2009
), and lower FA values throughout the CC (Barnea-Goraly et al. 2009
). It has been suggested that maldevelopment of the CC and potential impaired communication between hemispheres may affect brain maturation in pediatric BPD (Bellani et al. 2009
FIG. 1. Three-dimensional demonstration of corpus callosum (CC) (a) and anterior commissure (AC) (b). In panel (a), blue, green, orange, yellow, cyan, and red color indicate the CC fibers connecting to orbital, frontal, parietal, occipital, temporal lobe, and (more ...)
To our knowledge, no DTI studies have reported findings in the anterior commissure (AC), a relatively small tract connecting the temporal lobes and amygdala of both hemispheres (the AC connects the middle and inferior temporal gyri) () in BPD. The size of the AC has been postulated to play a role in emotional intelligence and social sensitivity (Clark et al. 2010
). Since individuals with BPD have deficits in both emotional and social functioning, our exploratory hypothesis is that the AC may play a role in the presentation of the disorder. The lack of reported alterations in the tensor metrics of the AC to date may be related to the small size of this structure and the low inherent resolution of DTI used in clinical practice.
In our preliminary study, we acquired high-resolution DTI scans from 10 youth with BPD and compared the DTI data with that of 10 age-matched healthy control subjects collected as a part of another research study (Rollins et al. 2009
). We focused on the commissural tracts, as the studies to date reporting disruption of interhemispheric communication in BPD may be related to the emotional deficits characteristic of the illness. We specifically compared FA values between groups for five segments of the CC and the AC. We hypothesized that there would be decreased FA in the CC for the group with BPD. We did not have a specific directional hypothesis for the AC, as no previous studies have reported DTI findings in this region for individuals with BPD, although we anticipated WM abnormalities in that region. In addition, post hoc
correlations between DTI scalars and scores on a measure of aggression were performed for the participants with BPD to explore the relationship between the structural aberration and behavior.