Toward an animal model of borderline personality disorder

Abstract

Background: Borderline personality disorder (BPD) is a pervasive psychiatric disorder characterized by emotion dysregulation, impulsivity, impaired self-perceptions, and interpersonal relationships and currently affects 1-3% of the US population as reported by Torgersen et al. (Arch Gen Psychiatry 58:590-596, Torgersen et al. 2001), Lenzenweger et al. (Biol Psychiatry 62:553-564, Lenzenweger et al. 2007), and Tomko et al. (J Personal Disord 28:734-750, Tomko et al. 2014). One major obstacle to our understanding of the neural underpinnings of BPD is a lack of valid animal models that translate the key known features of the disorder to a system that is amenable to study.

Objective: To summarize the etiology, major symptoms, and symptom triggers of BPD and then propose a blueprint for building an animal model of BPD by choosing key components of the disorder that can be implemented in rodents.

Results: We identify the role of early life stress and subsequent mild stress in adulthood as contributing etiological factors and the potential use of altered communication between frontal cortices and the amygdala in extinction and habituation, increased impulsivity, dysregulation of the hypothalamic pituitary axis (HPA), and increased neuroinflammation as biological markers of BPD. Building upon these features of BPD, we propose a two-hit animal model that uses maternal abandonment to alter maturation of the HPA axis and mild secondary adult stress to evoke behavioral symptoms such as increased impulsivity and impaired extinction, habituation, and social interactions.

Conclusion: Through exploration of the etiology, symptom presentation, and altered neurological function, we propose an animal model of BPD. We believe that a number of existing animal paradigms that model other mental health disorders should be combined in a unique way to reflect the etiology, symptom presentation, and altered neurological function that is evident in BPD. These model, when compared with available human data, will inform research and treatment in humans for better understanding of systems from the micro-molecular level to more global physiology underlying BPD.

Keywords: Arousal regulation; Borderline personality disorder; Early life stress.

Figure 1.

A suggested layout for an animal model dedicated to the study of BPD. The timeline refers to development of mice, and confers a model with early life stress as the etiology established pre-weaning, followed by mild stress administration in adulthood, and outcome measures immediately after the trigger. We suggest several possibilities for inducing Early Life Stress, and for Mild Adult Stress. The suggested methods for stress induction and outcome testing are a guide, and the specific constellation of chosen tests will depend on each researcher’s interests. For the most accurate behavioral model of clinical BPD, we recommend that deficits in a test of social interaction or the 3-chamber sociability test are established along with a deficit in at least one of the following behavioral measures: Fear extinction consolidation, Habituation, Delay Discounting (see Section 7.2). Physiology measures have expected outcomes based on previous findings (see Section 7). Repeated mild stressor-outcome measures are appropriate.