Love in a Borderline Personality

https://commons.wikimedia.org/wiki/File:Oxytocin_color.svg

https://commons.wikimedia.org/wiki/File:Oxytocin_color.svg

Love sucks. It makes people act in ways they can’t predict and gives them weird fluttering feelings in their stomach. However, healthy people at least tend to know what to expect with love, and modern research has even discovered the molecules involved in the development of romantic attraction, both emotionally and physiologically. One of cupid’s arrows is oxytocin (1) and while it is almost universally acknowledged as the “love hormone,” there is some evidence pointing to this same molecule as a cause behind the erratic and destructive behavior seen in people with borderline personality disorder (BPD).

Professor Ryan Bogdan’s BRAIN (Behavioral Research And Imaging Neurogenetics) lab here at Washington University found that childhood maltreatment has a statistically significant intergenerational continuity (Paul, in review 2019). While not the direct cause of this unfortunate tendency, parental borderline personality pathology (BPP) was noted to be associated with familial instability and unstable relationships leading to childhood maltreatment. Members of the abused generation, in turn, are more likely to abuse their own children, ultimately perpetuating this vicious cycle. Why does BPD have such a strong impact on familial relationships? From analysis of scientific literature, it would be reasonable to conclude that rather than just being the generalization of BPD symptomatic behavior to the domestic, family context, there is a unique interaction between the oxytocin signaling involved in parent-child relationships and BPP which exacerbates destructive BPD behavior and transforms it into child abuse. Therefore, the biological cause of child abuse in households with at least one BPP-presenting parent may be the very same biomolecular pathway as the one associated with love and parental protective instincts.

An estimated 1% of American adults have BPD with 3 million cases per year in the US (2). However, despite its prevalence, BPD continues to be a mysterious psychiatric disorder with neither concrete genetic causes nor molecular pathways to explain its symptoms. These nine symptoms outlined in the DSM-V (Diagnostic and Statistical Manual of Mental Disorders)  include sufficient overlap with bipolar disorder (BD) such that 40% of BPD patients were previously misdiagnosed with BD, (3) and one study even found a 58% comorbidity for BPD and schizophrenia (SCZ) (4). Additionally, the complexity of BPD has posed numerous roadblocks for researchers, including the lack of  development of animal models, because the symptoms and systems associated with the disease are simply too difficult to properly model in any animal. However, these challenges have not deterred scientists, and in 2017, a genome-wide association study (GWAS) identified two particularly hopeful genes who passed the statistical analysis for suggestive evidence of association: PKP4 and DPYD (5). Of particular note in PKP4’s resumé is its involvement in cell-adhesion molecules, junctional plaques, and cadherin function. The cadherin family is composed of hundreds of different type 1 transmembrane proteins governing Calcium-dependent adhesion and assisting in synapse morphogenesis and specificity. A 2012 study previously implicated cadherins in neuropsychiatric disorders such as BD and autism (6), but BPD was not on that list. However, extensive research has been done on cadherin expression in amygdalar development, and one such study found cadherin expression to delineate postnatal and adult mouse amygdala divisions (7). In fact, by comparing the regional concentration differences of just 13 cadherin and proto-cadherin subtypes through combinatorial expression mapping, the researchers were able to clearly distinguish between amygdalar and many other cortical regions. In other words, by staining individual cadherin types separately and then finding distinct patterns in combinations of the resulting images, researchers were able to accurately identify subcortical structures and their respective constituent regions.

In BPD patients, amygdalar volume has been shown to be significantly smaller than in healthy individuals (8), but amygdalar activation is far greater in BPD patients when experiencing negative stimuli (9). These functional and structural differences in the disease illustrate the activity of some biological dysfunction, potentially in cadherin-supported amygdala development. The heightened amygdala activity corresponds to decreased oxytocin levels in BPD (10) which then fail to suppress cortisol (11), leading to greater subjective stress in BPD patients (12). Cadherins don’t just play a role in amygdalar structure, but also in the paraventricular nucleus of the hypothalamus (PVN). The PVN responds to physiological changes such as stress, so given that BPD and PTSD are both frequently caused by childhood abuse, it isn’t a far stretch to say that in addition to cortical structure, BPD also affects adult oxytocin plasma levels by stress-induced complications in PVN function.

Beyond the broad name of the “love hormone”, oxytocin is also involved in a number of everyday, human functions. Amygdalar oxytocin allows us to learn emotional empathy (13) and manage our fears (14) as well as fulfill numerous other equally important psychological roles. Then why does oxytocin administration to BPD patients induce trust issues rather than promote empathy and agreeable behavior (15)? With such a broad question many questions and tangents may be taken to respond, but a 2015 paper nicely summarizes the information necessary to understand a possible explanation. Oxytocin injection into mouse basolateral and central amygdala prior to a fear stimulus increased fear response and decreased fear acquisition (14). In humans, should these regions develop improperly due to, perhaps, cadherin dysfunction from a mis- or overexpressed PKP4 gene, irrational responses to innocuous circumstances as is characteristic of BPD doesn’t seem so far-fetched anymore.

With a low baseline oxytocin in BPD, a propensity for stress from raised cortisol levels, the elevation of oxytocin in a family setting may induce similar effects as the oxytocin intranasal administration or injection as in the Bartz and Campbell-Smith studies, respectively. The improperly developed BPD amygdala, poorly receiving the already relatively low oxytocin may cause BPD parents to poorly cope with stress in a domestic setting and therefore inadvertently abuse their children, causing PTSD or significant emotional damage and thus inducing the perpetuation of the abuse which the parent may have been exposed to in a subsequent generation. Without concrete data to back or deny this hypothesis, it’s impossible to say whether such a meta-analysis of currently available literature is right or wrong. However, with every passing year, the tools at the disposal of researchers continue to drastically improve and so soon enough, we’ll find what’s behind the curtain of BPD and be able to use that knowledge to help combat the psychological disease and the child abuse it may cause.

Edited by: Chase Breimeier




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