Genetic associations with borderline personality disorder and related traits and behaviors

Casey Roy Guillot

Abstract

Borderline personality disorder (BPD) and related traits and behaviors have been linked to a number of neurotransmitter systems, including serotonin, norepinephrine, GABA, and dopamine. Because three human single-nucleotide polymorphisms (SNPs), COMT rs4680, GABRA2 rs279871, and SNCA rs356195, have been linked to the above-mentioned neurotransmitter systems, they may be associated with BPD and related traits and behaviors. The purpose of the current study is to examine associations of COMT rs4680, GABRA2 rs279871, and SNCA rs356195 with both categorical and continuous measures of BPD and with continuous measures of impulse control and self-harm in a nonclinical sample. Healthy volunteers were categorized into genotypic and allelic groups, and then those groups were compared in order to determine if certain genotypes and alleles are associated with specific categorical and continuous outcomes. COMT rs4680 was the only SNP related to both categorically and continuously measured BPD as well as to impulse control and self-harm scores. However, results with COMT rs4680 often were suggestive of heterosis, which presents difficulty in explaining. In regard to the other SNPs, GABRA2 rs279871 was related to BPD, impulse control, and self-harm scores, whereas SNCA rs356195 was only related to the former two. All three SNPs yielded some gender-specific results, which may be explained by gender differences in one or more of the following: COMT activity, steroid hormone and neurosteroid levels, neurosteroid effects, regional brain structure, and DA and alpha-synuclein systems. In conclusion, it appears that COMT, GABRA2, and SNCA may influence the development of BPD and related traits and behaviors.