Borderline personality disorder (BPD) may be associated with smaller hippocampi in comparison to hippocampal size in controls. However, specific pathology in hippocampal substructures (i.e., head, body and tail) has not been sufficiently investigated. To address hippocampal structure in greater detail, we studied 39 psychiatric inpatients and outpatients with a DSM-IV diagnosis of BPD and 39 healthy controls. The hippocampus and its substructures were segmented manually on magnetic resonance imaging scans. The volumes of hippocampal substructures (and total hippocampal volume) did not differ between BPD patients and controls. Exploratory analysis suggests that patients with a lifetime history of posttraumatic stress disorder (PTSD) may have a significantly smaller hippocampus – affecting both the hippocampal head and body – in comparison to BPD patients without comorbid PTSD (difference in total hippocampal volume: −10.5%, 95%CI −2.6 to −18.5, significant). Also, patients fulfilling seven or more DSM-IV BPD criteria showed a hippocampal volume reduction, limited to the hippocampal head (difference in volume of the hippocampal head: −16.5%, 95%CI −6.1 to −26.8, significant). Disease heterogeneity in respect to, for example, symptom severity and psychiatric comorbidities may limit direct comparability between studies; the results presented here may reflect hippocampal volumes in patients who are “less” affected or they may simply be a chance finding. However, there is also the possibility that global effects of BPD on the hippocampus may have previously been overestimated.
Borderline personality disorder (BPD) has a lifetime prevalence of approximately 6% and more commonly affects women than men. Patients with BPD show high rates of comorbidity with other psychiatric disorders such as affective and anxiety disorders including major depression (MD) and posttraumatic stress disorder (PTSD) – with approximately 20% and 40%, respectively, showing overlapping diagnoses (Grant et al., 2008).
Several studies in the last decade have investigated whether regional brain volumes in patients with BPD differ from corresponding volumes in controls: BPD has been associated with a reduction of right and left hippocampal volumes in most reports (Driessen et al., 2000, Schmahl et al., 2003, Tebartz van Elst et al., 2003, Brambilla et al., 2004, Irle et al., 2005, Zetzsche et al., 2007 and Weniger et al., 2009).
Recent meta-analyses (Nunes et al., 2009, Rodrigues et al., 2011 and Ruocco et al., 2012) report moderate aggregated effect sizes of volume reduction (e.g. Cohen׳s d of up to 0.7 ( Ruocco et al., 2012)); however, there is also substantial variability across studies, signaling heterogeneity of the cohorts studied. Moreover, a putatively smaller hippocampus may not reflect a causal pathogenetic pathway, but be more indirectly associated with the disorder via a variety of factors such as the severity of symptoms over time or treatment effects. Comorbidity may also act as a confounder or mediator: MD ( MacQueen et al., 2003) and PTSD ( Felmingham et al., 2009) have been shown to be associated with reduced hippocampal volumes. In fact some studies have found that hippocampal volumes are not smaller in BPD patients unless they have comorbid PTSD ( Schmahl et al., 2009), while other studies have inconclusive findings.
Although pathogenesis remains unclear, there is pathophysiologic plausibility that certain pertinent stressors present in, but not specific to, BPD, may act in concert with a given individual susceptibility to culminate in damage to the hippocampus (Geuze et al., 2005).
Also, exposure may differentially interact with specifically vulnerable hippocampal substructures – ventral parts of the hippocampus are predominately involved in behavioral inhibition, emotional memory, and stress processing, while dorsal aspects are thought to be more relevant to spatial and cognitive processing with strong neocortical connections (Fanselow and Dong, 2010) – differential functions that may result in patterns of preferential damage. Studies recruiting patients with other psychiatric disorders have highlighted that the hippocampus shows disease-specific patterns of non-uniform volume reduction (e.g. depression (Maller et al., 2007)). There has been only one previous study that has specifically investigated potential substructural pathology in the hippocampus in patients with BPD (O׳Neill et al., 2013), which found reduced volumes in all substructures in the left hippocampus, but affecting only the tail in the right hippocampus, in comparisons with healthy controls.
The study׳s planned goal was to investigate potential differences in hippocampal substructural volumes associated with BPD using manual volumetry of the hippocampus, extending results from a previous study (Driessen et al., 2000). Additionally, exploratory post-hoc analyses of the effects of comorbidity and a proxy for BPD severity were performed. This study also complements a recent study of our workgroup that looked at group differences in whole-brain and region-of-interest gray matter concentration using a voxel-based morphometry approach in a subset of the population presented here (Labudda et al., 2013).
