Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects.

A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition–Revised criteria) participated in these studies. The prolactin response to fenfluramine (a measure of serotonin function) was obtained for 110 subjects; growth hormone response to clonidine (a measure of noradrenergic function) was obtained for 77 subjects, while homovanillic acid (HVA) at baseline, an index of dopaminergic function, was available for 103 subjects. Measures of central neurotransmitter function (dopaminergic, serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylglycol, respectively) were available for 36 subjects. Separate regression analyses utilizing each of the hypothesized associations, where the TPQ total scores were used as the dependent measures and the biologic indices were the independent measures were conducted. Exploratory correlational analyses between these biologic measures and the four dimensions of the TPQ (and its subscales) were also conducted. (Correlations are reported if they would remain significant at P<.01 level after Bonferroni correction for multiple comparisons across the six neuroendocrine measures).

In the regression analyses, there was a trend association between CSF and plasma HVA in predicting novelty-seeking (P<.07). No other significant associations were found in the other three measures. Regarding the individual correlational analyses, the persistence scale of the TPQ was significantly positively correlated with the growth hormone response to clonidine (r=.30, P<.008). The sentimentality subscale (reward dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45, P<.001), while the attachment subscale (also reward dependence) was correlated with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002).

Limited support was provided for a relationship between monoamines, particularly dopamine and novelty-seeking as well as norepinephrine and reward dependence but other hypothesized relationships were not supported by these measures.

Clinical and pre-clinical data suggest the possibility of a facilitory role for norepinephrine (NE) in impulsive-aggressive behavior. While clinical studies have focused on putative central measures of NE activity, few studies have been published using peripheral measures. In this study, the relationship between plasma free NE metabolite, plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG), and impulsive aggression was explored in subjects with personality disorder.

Subjects were 30 male subjects with personality disorder in whom basal plasma free MHPG concentrations were obtained. Aggression was assessed using the Life History of Aggression (LHA) assessment and the Buss-Durkee Aggression scales; impulsivity was assessed using the Barratt Impulsiveness and the Eysenck Personality Questionnaire Impulsivity scales.

A significant inverse correlation was found between LHA-Aggression and pMHPG in these subjects. Correlations with other behavioral measures were not statistically significant. pMHPG was significantly lower among subjects with borderline personality disorder but not significantly lower after controlling for LHA-Aggression scores.

These data suggest that pMHPG is inversely correlated with life history of aggression in subjects with personality disorder and that central and/or peripheral NE may play a role in modulating aggressive behavior in these subjects.

Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples.

This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution.

Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men.

These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder.

Dissociation is a prominent feature in some individuals with borderline personality disorder (BPD), yet our understanding of the meanings and implications of prominent dissociation in BPD remains limited. The purpose of this study was to investigate the relationship between dissociation and childhood trauma in BPD and to explore the relationships of dissociation and trauma to various personality features of BPD.

Twenty BPD subjects and 24 healthy comparison subjects of similar age and gender were administered the Dissociative Experiences Scale, the Childhood Trauma Questionnaire—short form, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the Relationship Style Questionnaire, and the Schema Questionnaire.

The BPD group exhibited greater dissociation and childhood trauma, as well as greater pathology in most personality variables, compared with the healthy group. Dissociation in BPD was not significantly related to total childhood trauma, but only to emotional neglect, which accounted for 23% of the variance in dissociation scores.

Within the BPD group, dissociation was associated with fearful attachment and immature defenses, while total childhood trauma and emotional neglect were associated with overconnection and disconnection schemata. This is a preliminary study with a small sample size, yet the correlates of dissociation in BPD merit further investigation.

This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174).

Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure.

A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21–.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores.

This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder.