Past, present, and future of genetic research in borderline personality disorder

Abstract

Borderline Personality Disorder (BPD) is a major mental illness with a lifetime prevalence of approximately 1-3%, characterized by a persistent pattern of instability in relationships, mood, impulse regulation, and sense of self. This results in impulsive self-damaging behavior, high suicide rates, and severe functional impairment. BPD has a complex, multifactorial etiology, resulting from an interaction among genetic and environmental substrates, and has moderate to high heritability based on twin and family studies. However, our understanding of the genetic architecture of BPD is very limited. This is a critical obstacle since genetics can pave the way for identifying new treatment targets and developing preventive and disease-modifying pharmacological treatments which are currently lacking. We review genetic studies in BPD, with a focus on limitations and challenges and future directions. Genetic research in BPD is still in its very early stages compared to other major psychiatric disorders. Most early genetic studies in BPD were non-replicated association studies in small samples, focused on single candidate genes. More recently, there has been one genome-wide linkage study and a genome-wide association study (GWAS) of subclinical BPD traits and a first GWAS in a relatively modest sample of patients fulfilling full diagnostic criteria for the disorder. Although there are adequate animal models for some of the core dimensions of BPD, there is a lack of translational research including data from animal models in BPD. Research in more pioneering fields, such as imaging genetics, deep sequencing and epigenetics, holds promise for elucidating the pathophysiology of BPD and identifying new treatment targets.

Neuroimaging Studies of Suicidal Behavior and Non-suicidal Self-Injury in Psychiatric Patients: A Systematic Review

“…The prevalence of this condition is estimated between 0.5 and 5.9% in the general population ( 69 ). It is a disease for which few genetic studies have been performed ( 70 ), and an almost negligible amount of research has been done to determine the brain regions involved in SB and NSSI in this specific disorder. Our methodology found three neuroimaging studies investigating brain structure and suicidality in BPD patients (summarized in Table 5 ).…”

Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

“…Behavioral studies in humans suggest that rs1006737 is linked to facial emotion recognition in both healthy individuals and patients with BD [167,168]. Some studies suggest that rs1006737 is also associated with borderline personality disorder in females, but not males [169,170]. Furthermore, rs1006737 has significant association with reduced baseline affective startle modulation in healthy males.…”

Neurological soft signs correlation with symptom severity in borderline personality disorder

“…While there was no specific focal neurological deficit identified in patients with BPD [8], there was an increased observation of mild neurological soft signs in this population (NSS) [9,10]; in fact, De la Fuente et al [9] in their study found that 13 of the soft neurological signs were significantly higher in borderline personality disorder patients than controls.…”