Neuropsychological functions in women with borderline personality disorder and a history of suicide attempts

Abstract: Borderline personality disorder (BPD) is a complex psychiatric disorder that leads to intense suffering for afflicted individuals, and extensive use of health care resources. Self-injurious and suicidal behaviors are common among individuals diagnosed with BPD, and as many as 10% of these will eventually die from suicide. BPD presents a clinical challenge as the condition is not well-understood, and has been notoriously difficult to treat. Recent research has confirmed the complex etiology and symptomatology of BPD, and a number of neurobiological and cognitive abnormalities have been indicated. Elucidating such underpinnings of BPD is called for in order to render effective treatment possible. Of great importance is to identify factors that contribute to the extraordinarily high rate of suicidal and self-injurious behavior, and the investigation of gene-environment interactions that occur when the effect of environmental stress is conditional on the genotype of the individual. In this thesis we examined executive functions such as social problem solving and decision-making, and we examined memory functions, and affective symptoms, in 51 (77 in Study IV) women with BPD who had made several suicide attempts. These factors were studied in relation to co-occurring diagnoses of depression and post-traumatic stress disorder (PTSD), traumatic experiences, suicidal and self-harming behavior, and variants of genes within the serotonergic system in order to examine possible associations between them. These results were compared with those of 30 non-clinical control participants who were matched to the BPD group for age and education. In Study I, we examined autobiographical memory in order to study whether the clinical impression that persons with BPD have problems in remembering specific details of their own experiences, holds good. We also studied the role of autobiographical memory in social problem solving, since specific personal memories provide a database of possible solutions to social dilemmas, and its relation to depression and PTSD, traumatic experiences, and level of suicidal and self-harming behavior. It was shown that the individuals in the BPD group produced significantly less specific autobiographical memories than controls. This was associated with difficulties in solving social problems, but not with concurrent diagnoses of depression or PTSD, traumatic experiences, or level of suicidal and self-harming behavior. In Study II, we investigated executive functions of concept formation, goal maintenance, planning ability and working memory in relation to suicidal and self-injurious behaviors. Executive dysfunctioning may be one risk factor for self-harming behavior because such functions are important determinants for adequate cognitive and emotional self-regulation. The BPD group showed greater problems with goal maintenance and planning ability than controls. In addition, deficits in planning ability were associated with life-time number of non-suicidal self-injurious events, and poor concept formation was associated with lifetime number of suicide attempts. In Study III, we examined emotionally controlled decision-making, indicated to be impaired in individuals with BPD. Serotonin dysfunction has been associated with both decision-making and BPD, and for this reason we also studied the relationship between impaired decision-making and a variant of the gene coding for tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis. The results indicated decision-making problems in persons with BPD, and that these difficulties were associated with a specific haplotype of the TPH-1 gene. In Study IV, we tested for an association between variants of the serotonin transporter gene polymorphisms 5-HTTLPR and rs25531 and relevant clinical features of BPD. The presence of one or two copies of the short (s) allele of the 5-HTTLPR polymorphism, and the rs25531 G allele, have been associated with reduced serotonin transporter expression and function, and vulnerability to affective disorders. The study demonstrated that individuals with BPD who carried two s alleles of the 5-HTTLPR (including rs25531 G variants) reported more core borderline symptoms, depression, and anxiety, and obsessivecompulsive behavior, but not suicidal or self-injurious behavior. In conclusion: the present thesis describes specific impaired functions in individuals with BPD and a history of suicide attempts. These findings concern problems with autobiographical memory associated with the core difficulties of BPD in solving social problems. Further, we show that executive dysfunctions are coupled to some of the most distressing and clinically relevant symptoms of BPD, namely suicidal and selfharming behaviors. Some of the indicated impairments, together with several psychiatric symptoms, seem to be related to serotonin system gene variants, indicating serotonergic dysfunction. Based on these findings, we propose that the core problems of BPD, such as impaired emotionally relevant decision-making, are related to serotonergic function in prefrontal areas.