<p>Borderline personality disorder, trauma, and the hypothalamus–pituitary–adrenal axis</p>

Abstract

Borderline personality disorder (BPD) is a complex psychiatric illness for which treatment poses a significant challenge due to limited effective pharmacologic treatments, and under-resourced psychological interventions. BPD is one of the most stigmatized conditions in psychiatry today, but can be understood as a modifiable, neurodevelopmental disorder that arises from maladaptive responses to trauma and stress. Stress susceptibility and reactivity in BPD is thought to mediate both the development and maintenance of BPD symptomatology, with trauma exposure considered an early life risk factor of development, and acute stress moderating symptom trajectory. An altered stress response has been characterized in BPD at the structural, neural, and neurobiological level, and is believed to underlie the maladaptive behavioral and cognitive symptomatology presented in BPD. The endocrine hypothalamus-pituitary-adrenal (HPA) axis represents a key stress response system, and growing evidence suggests it is dysfunctional in the BPD patient population. This theoretical review examines BPD in the context of a neurodevelopmental stress-related disorder, providing an overview of measurements of stress with a focus on HPA-axis measurement. Potential confounding factors associated with measurement of the HPA system are discussed, including sex and sex hormones, genetic factors, and the influence of sample collection methods. HPA-axis dysfunction in BPD largely mirrors findings demonstrated in post-traumatic stress disorder and may represent a valuable neuroendocrine target for diagnostic or treatment response biomarkers, or for which novel treatments can be investigated.

“Esketamine” in Borderline Personality Disorder: A Look Beyond Suicidality

“…Coccaro et al reported direct correlations between cerebrospinal fluid (CSF) glutamate levels and composite measures of aggression, impulsivity, and impulsive aggression in healthy subjects and patients with personality disorders [ 16 ]. Glutamate-mediated neuroinflammation and HPA axis dysregulation are seen with BPD, early life trauma, and impulsivity [ 17 , 10 ]. Esketamine’s potential action on patients with BPD can be partially explained by its very well-documented effect on the glutamate receptor antagonism.…”

“…Both physical and psychological pain converge into the opioid system, and low levels of endogenous opioids in BPD lead to chronic dysphoria, lack of sense of well-being, and a chronic feeling of emptiness. Self-harm attempts have been shown to increase opioid levels in patients with BPD [ 17 ]. Ketamine recalibrates and improves basal opioid levels, which can hypothetically improve symptoms of BPD [ 10 ].…”

Menstrual Cycle in Trauma-Related Disorders: A Mini-Review

“…There is overlap in the neurochemistry and neurostructural changes observed in PTSD, BPD and cPTSD, with no clear differentiation between the three conditions in regards to HPA axis function or subsequent alterations ( 29 ). For instance, HPA axis overactivity has been implicated in BPD ( 60 ) and PTSD ( 56 ), and this dysfunction in both disorders is believed to closely mirror each other ( 58 ).…”

Understanding the Relationship Between Sleep Problems in Early Childhood and Borderline Personality Disorder: A Narrative Review

“…The HPA axis represents a key stress response system, and growing evidence suggests that it is dysfunctional in the BPD population. 6 Further, sleep, and in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA can lead to sleeplessness. 7…”