NEUROTRANSMITTER DYSFUNCTION IN PATIENTS WITH BORDERLINE PERSONALITY DISORDER

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Borderline personality disorder (BPD) is a severe personality disorder characterized by potentially self-damaging impulsivity, inappropriate or uncontrolled anger, recurrent suicidal threats or gestures, physically self-damaging acts, and disturbances in identity and interpersonal relations. It is associated with high levels of distress, significant impairment in social and occupational functioning, and a 10% lifetime risk for suicide. Approximately 2% of the population meets criteria for BPD. It is more often diagnosed in women and is more widespread among first-degree relatives of those with the disorder.

BPD and the other personality disorders have traditionally been understood in the context of psychodynamic, psychosocial, or behavioral approaches. Research over the past 2 decades has demonstrated the significance of biological factors and traumatic early life experiences that may have long-lasting biological sequelae. BPD is one of several disorders associated with a history of childhood physical or sexual trauma.23, 28, 62 Also, several neurobiological correlates of BPD have been identified. Two potentially biologically mediated traits may contribute to BPD— affective instability and impulsive aggression. Although some studies have shown that BPD runs in families,47 twin studies suggest that BPD per se is not inherited, but its components, impulsive aggression and affective instability, are partially heritable.77 Evidence from neurochemical assays, receptor-density studies, neuroendocrine-challenge paradigms, functional neuroimaging studies, and candidate-gene studies have converged to identify several neurotransmitter systems that may be associated with the neurobiology of BPD. This article examines the neurotransmitter systems associated with impulsive aggression and affective instability of BPD.

Impulsive aggression in patients with BPD is characterized by self-destructive acts, including suicidal and parasuicidal behavior, and outwardly directed aggression. Affective instability is defined by DSM-IV as “intense episodic dysphoria, irritability, or anxiety, usually lasting a few hours and only rarely more than a few days.”1a Psychosocial cues, most typically frustrations, humiliations, losses, separations, and rejections, often trigger the affect swings in BPD. It may be useful to look separately at two components of affective instability, one encompassing the lability of affect, and the other, the reactivity to environmental cues. Affective instability may interfere with the ability to develop a stable perception of self or others and may result in difficulty in maintaining self-esteem. An interaction may exist between affective instability and poor impulse control, in which intense affective storms trigger impulsive behavior.

Section snippets

Serotonin

Dysfunction in the serotonin (5-HT) system has been associated with self-directed and non–self-directed impulsive aggression. Early evidence for this association emerged from studies of violent suicide attempters and of individuals who had committed violent acts. One of the first approaches to assess the activity of the serotonin 5-HT system was to measure the concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the cerebrospinal fluid (CSF). In a study of violent

NEUROCHEMISTRY OF AFFECTIVE INSTABILITY

Although the neurochemistry of affective instability is less understood than that of impulsive aggression, preclinical and clinical research suggests that dysregulations in cholinergic, noradrenergic (NE) or gamma-aminobutyric acid (GABA)-minergic systems may play an important role in affective instability. Also, the instability may result from unstable feedback regulatory systems at the level of neural networks, synaptic neurotransmission, or intracellular signal transduction.

DISCUSSION

Impulsive aggression and affective instability are two traits present in patients with BPD for which evidence associates disturbances with neurotransmitter function. Although each of these traits may contribute individually to certain personality disorders (e. g., impulsive aggression to antisocial personality disorder, or affective instability to histrionic personality disorder), their co-occurrence may particularly predispose to BPD. Certain life experiences, such as ongoing abuse or neglect

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    Address reprint requests to Harold W. Koenigsberg, MD, Mount Sinai School of Medicine, Bronx Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468

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