Pathoetiology and pathophysiology of borderline personality: Role of prenatal factors, gut microbiome, mu- and kappa-opioid receptors in amygdala-PFC interactions.

Affiliation

CRC Scotland & London, Eccleston Square, London, UK. Electronic address: [Email]

Abstract

The pathoetiology and pathophysiology of borderline personality disorder (BPD) have been relatively under-explored. Consequently, no targetted pharmaceutical treatments or preventative interventions are available. The current article reviews the available data on the biological underpinnings of BPD, highlighting a role for early developmental processes, including prenatal stress and maternal dysbiosis, in BPD pathoetiology. Such factors are proposed to drive alterations in the infant's gut microbiome, in turn modulating amygdala development and the amygdala's two-way interactions with other brain regions. Alterations in opioidergic activity, including variations in the ratio of the mu-and kappa-opioid receptors seem a significant aspect of BPD pathophysiology, contributing to its comorbidities with depression, anxiety, impulsivity and addiction. Stress and dysphoria are commonly experienced in people classed with BPD. A growing body of data, across a host of medical conditions, indicate that stress and mood dysregulation may be intimately associated with gut dysbiosis and increased gut permeability, coupled to heightened levels of oxidative stress and immune-inflammatory activity. It urgently requires investigation as to the relevance of such gut changes in the course of BPD symptomatology. Accumulating data indicates that BPD symptom exacerbations may be linked to cyclical variations in estrogen, in turn decreasing serotonin and local melatonin synthesis, and thereby overlapping with the pathophysiology of migraine and endometriosis, which also have a heightened association with BPD. Future research directions and treatment implications are indicated.

Keywords

Amygdala,Borderline personality,Depression,Estrogen,Gut microbiome,Melatonin,Prefrontal cortex,Treatment,kappa-opioid receptor,mu-opioid receptor,

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