Borderline personality disorder: stress reactivity or stress generation? A prospective dimensional study.

BACKGROUND: Individuals diagnosed with borderline personality disorder (BPD) often describe their lives as stressful and unpredictable. However, it is unclear whether the adversity faced by those with BPD is a product of stress reactivity or stress generation. Here, we examined the dynamic, prospective associations between BPD and stressful life events over 3 years. Given the heterogeneity present in BPD, we sought to understand which empirically derived dimensions of this heterogeneous disorder explain stress reactivity v. stress generation. METHODS: Participants included 355 individuals diagnosed with BPD and followed longitudinally at three annual assessments. Auto-regressive cross-lagged panel models were used to examine prospective associations between stressful life events and three latent dimensions implicated in BPD: negative affect, disinhibition, and antagonism. RESULTS: Antagonism and disinhibition, but not negative affect, prospectively predicted dependent stressful life events (events the individual may have some role in). Evidence for decompensation under stress was more tenuous, with independent stressful life events (those presumably outside the individual's control) predicting increases in negative affect. CONCLUSIONS: Our longitudinal study of a well-characterized clinical sample found more evidence for stress generation than for stress-induced decompensation in BPD. Stress generation in BPD is driven by externalizing dimensions: antagonism and disinhibition. These results highlight the utility of empirically derived dimensions for parsing heterogeneity present in BPD, leading to improvements in diagnostic evaluation, clinical prediction, and individualized approaches to treatment planning.

Stimulus valence, episodic memory, and the priming of brain activation profiles in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by instability in affective regulation that can result in a loss of cognitive control. Triggers may be neuronal responses to emotionally valenced context and/or stimuli. 'Neuronal priming' indexes the familiarity of stimuli, and may capture the obligatory effects of affective valence on the brain's processing system, and how such valence mediates responses to the repeated presentation of stimuli. We investigated the effects of affective valence of stimuli on neuronal priming (i.e. changes in activation to repeated presentation of stimuli), and if these effects distinguished BPD patients from controls. METHODS: Forty BPD subjects and 25 control subjects (age range: 18-44) participated in an episodic memory task during fMRI. Stimuli were presented in alternating epochs of encoding (six images of positive, negative, and neutral valence) and recognition (six images for 'old' v. 'new' recognition). Analyses focused on inter-group differences in the change in activation to repeated stimuli (presented during Encoding and Recognition). RESULTS: Relative to controls, BPD showed greater priming (generally greater decrease from encoding to recognition) for negatively valenced stimuli. Conversely, BPD showed less priming for positively valenced stimuli (generally greater increase from encoding to recognition). CONCLUSION: Plausibly, the relative familiarity of negative valence to patients with BPD exerts an influence on obligatory responses to repeated stimuli leading to repetition priming of neuronal profiles. The specific effects of valence on memory and/or attention, and consequently on priming can inform the understanding of mechanisms of altered salience for affective stimuli in BPD.

Bridging the Gap Between Remission and Recovery in BPD: Qualitative Versus Quantitative Perspectives.

The 10-year outcome for patients with borderline personality disorder (BPD) is diagnostic remission in 85% to 93%; however, less than half achieve good social and vocational functioning, and few attain full psychosocial recovery. To assess the gap between diagnostic remission and psychosocial recovery, quantitative measures of outcome were compared with narrative reports of psychosocial functioning in 150 BPD subjects followed prospectively from 2 to 31 years (mean 9.94 years). Subjects with the best and the worst outcomes were compared on symptom changes over time, and on efforts to improve psychosocial functioning. At intake, poor outcome subjects were more impaired than those with good outcomes, with more borderline psychopathology, hospitalizations, and poverty. At follow-up, 53.8% of good outcome subjects complained of continuing problems with depression, 33.3% with anger and impulse control, and 25.6% with unstable relationships. Despite objective measures of improvement, narrative reports documented residual BPD symptoms, comorbidity, and unemployment interfering with psychosocial recovery.

Gender, personality, and serotonin-2A receptor binding in healthy subjects.

The vulnerability to mood disorders, impulsive-aggression, eating disorders, and suicidal behavior varies greatly with gender, and may reflect gender differences in central serotonergic function. We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT(2A) receptor binding in 21 healthy subjects using [18F]altanserin and PET neuroimaging. Binding potentials in pre-defined regions-of-interest (ROI) were calculated using the Logan graphical method, corrected for partial volume effects, and compared by gender with age co-varied. SPM analysis was used for voxel level comparisons. Altanserin binding (BP(P)) was greater in male than female subjects in the following nine ROIs: hippocampus (HIP) and Lt. HIP, lateral orbital frontal cortex (LOF) and Lt. LOF, left medial frontal cortex (Lt. MFC), left medial temporal cortex (Lt. MTC), left occipital cortex (Lt. OCC), thalamus (THL) and Lt. THL. Differences in Lt. HIP and Lt. MTL remained significant after Bonferroni correction. Gender differences were noted in the co-variation of psychological traits with BP(P) values in specific ROIs. Among males alone, aggression was negatively correlated with BP(P) values in Lt. LOF and Lt. MFC, and Suspiciousness positively correlated in LOF, Lt. LOF and Lt. MFC. Among female subjects alone, Negativism was positively correlated with BP(P) values in HIP, and Verbal Hostility in Lt. HIP. Altanserin binding in Lt. MTC was positively correlated with Persistence, with no significant gender effect. Gender differences in 5HT(2A) receptor function in specific ROIs may mediate expression of psychological characteristics such as aggression, suspiciousness and negativism. Future studies of 5HT(2A) receptor function and its relationship to behavior should control for gender.

Time, Age, and Predictors of Psychosocial Outcome in Borderline Personality Disorder.

In longitudinal studies, BPD symptoms diminish over time, though psychosocial functioning lags far behind. The effects of time and advancing age on BPD are poorly understood. We sought prospective predictors of psychosocial outcome and recovery in 150 BPD subjects followed 2 to 31 years (mean 9.94 years) using a multidimensional assessment method and biannual follow-ups. Time-in-study had no significant effect on achieving diagnostic remission in BPD, good psychosocial outcomes, meaningful interpersonal relationships, full employment, or total recovery; however, younger age was associated with social and vocational achievement independent of BPD remission. Significant contributions to psychosocial outcome were found for age, employment status, MDD, SUD, Any Anxiety Disorder, and Alcohol abuse/dependence (ALC). Remission from BPD was neither necessary or sufficient for good interpersonal relationships or full-time employment. Full-time employment and social and vocational adjustment (SAS-sr) predicted good psychosocial outcome. Axis I comorbidity with Any Anxiety Disorder, MDD, or SUD predicted poor outcome.

10-Year Outcome of Suicidal Behavior in Borderline Personality Disorder.

Prospective predictors of suicide attempts were assessed in 118 subjects with borderline personality disorder (BPD) after 10 or more years of follow-up. Mean (SD) time to follow-up was 14.4 (4.7) years. Subjects were predominately female (78.8%), Caucasian (81.4%), and of lower socioeconomic status. Initial recruitment was evenly balanced between inpatient, outpatient, and non-patient (community) sources. In the 10-year interval, 55 subjects (46.6%) attempted suicide. Compared to baseline, suicidal ideation, number of attempts, and non-suicidal self-injury diminished markedly. Core symptoms of BPD, substance abuse, and alcohol use disorders decreased significantly; however, major depressive disorder (MDD) remained constant at 50%. Forty-four percent of subjects had poor psychosocial, vocational, and economic outcomes. Psychosocial outcome was independent of suicide history and any treatment. Increased risk was associated with interval hospitalization prior to any attempt (illness severity), as well as poor social, vocational, and psychosocial functioning at baseline.

Affective interference in borderline personality disorder: The lethality of suicidal behavior predicts functional brain profiles.

BACKGROUND: Negative affective interference with executive cognition is associated with emotion dysregulation and behavioral dyscontrol in BPD, including a diathesis to suicidal and self-injurious behavior. While clinically well described, the neural basis of affective interference with central executive network function, and resulting suicidal behavior is poorly understood. METHOD: In an fMRI study, 23 BPD suicide attempters completed an affectively modified Continuous Performance Task(X-CPT), in which targets and distractors were rendered on Negative, Positive and Neutral Ekman faces, with a Distorted image as a behavioral baseline. Responses to targets were contextualized by the affective context of the face. Lethality Rating Scale scores (LRS) were modeled as the primary regressor of interest on activation peaks, with HamD scores covaried. RESULTS: In the Negative vs. Neutral contrast, LRS scores were inversely related to activation in the ACC, parietal precuneus, BG and OFC, with no positive relationships. Results were similar in the Negative vs Positive contrast. In the Neutral vs. Positive contrast, activations were much less extensive, with mixed positive and negative relationships. Contextualizing responses based on the effects of valence decreased participant's ability to distinguish between targets and distracters; however, no differences were observed between valence contexts. fMRI-estimated effects were not confounded by differences in behavioral sensitivity across contexts. LIMITATIONS: In this female-only sample, possible gender differences were not addressed. CONCLUSIONS: With negative affective interference, increased lethality of suicidal behavior in BPD predicted diminished neural activation in areas critical to executive cognitive function. Therapies diminishing affective interference may reduce risk of suicidal behavior.

Prospective predictors of suicide attempts in borderline personality disorder at one, two, and two-to-five year follow-up.

Efforts to identify reliable predictors of suicidal behavior in Borderline Personality Disorder have been confounded by the marked dimensional heterogeneity of the disorder, frequent comorbidity with other high risk disorders, debilitating social and vocational consequences of BPD over time. Using survival analyses, we assessed the predictive association between risk factors in each of these symptom domains and suicide attempts in BPD subjects followed for 12 months, 18-24 months and 2-5 years. The suicide attempt rate was 19% in the first year, 24.8% through the second year. The risk of suicidal behavior among 137 BPD subjects completing the first 12 months was increased by comorbid MDD and poor social adjustment. Outpatient treatment decreased short-term risk. Among 133 subjects completing 18-24 months in the study, the relative risk of a suicide attempt was increased by hospitalization (prior to any attempt), and poor social adjustment. Among 122 subjects followed for 2-5 years, increased risk was associated with hospitalization and medication visits (prior to any attempt), an attempt in the first year, and a low GAS score at baseline. Long term risk was decreased by "any outpatient treatment." Predictors of suicidal behavior in BPD change over time. MDD has a short-term effect on suicide risk, while poor social adjustment may increase risk throughout each follow-up interval. Assessing and supporting family, work, and social relationships may decrease suicidal behavior in BPD, and should be a principal focus of long-term treatment.

Mediators of the relationship between childhood sexual abuse and suicidal behavior in borderline personality disorder.

A history of childhood sexual abuse (CSA) increases the risk of suicidal behavior and the lifetime number of suicide attempts in adults with BPD. Despite a strong association, specific variables mediating the relationship between CSA and adult suicidal behavior in BPD have not been identified. This study examined risk factors for suicidal behavior as potential mediators of the relationship between CSA and suicide attempts in 151 men and women with BPD. Diagnostic, clinical, and psychosocial risk factors, as well as CSA, and suicidal behaviors, were assessed by standardized interviews or self-rated measures. Psychotic and schizotypal symptoms, and poor social adjustment, were associated with both CSA and suicidal behavior, and partially mediated the relationship between CSA and attempter status. Psychotic and schizotypal symptoms in BPD define a vulnerability to cognitive and perceptual distortions under stress. They increase the likelihood of suicidal behavior in BPD, especially in the absence of mitigating social support. A theoretical model for suicidal behavior in BPD is presented which integrates direct, mediated, and moderated pathways between childhood sexual abuse and temperament, adolescent and adult risk factors, and suicidal behavior.

5HT2A receptor binding is increased in borderline personality disorder.

BACKGROUND: Postmortem studies in suicide victims demonstrate an increase in the number of post-synaptic 5-HT(2A) receptor binding sites in ventral lateral and orbital frontal cortex. Diminished metabolic responses to serotonergic activation are noted in these areas in impulsive subjects with borderline personality disorder (BPD), a group at high risk for suicidal behaviors. We examined 5HT(2A) receptor binding potential (BP) in impulsive subjects with BPD, with positron emission tomography neuroimaging with [(18)F] altanserin. METHODS: Fourteen female subjects with BPD were assessed for Axis I comorbidity, depressed mood, impulsivity, aggression, suicidality, childhood abuse, and compared with 11 healthy female control subjects. The 5HT(2A) receptor binding was evaluated in prefrontal cortex, anterior cingulate, hippocampus, temporal lobe, occipital cortex, and thalamus. Data were analyzed with Logan graphical analysis and a four-compartment (4C) model. RESULTS: Hippocampal 5HT(2A) receptor binding was significantly increased in BPD subjects compared with control subjects in both Logan and 4C analyses, covarying for age. Hippocampal BP values were related to comorbid major depressive episode, with highest values found in non-depressed BPD subjects and lowest in healthy control subjects. The BP values were not related to depressed mood, impulsivity, aggression, suicidality, or childhood abuse. CONCLUSIONS: 5HT(2A) receptor binding is increased in the hippocampus of BPD subjects independent of depressed mood, impulsivity, aggression, suicidality, or childhood abuse. Dysregulation of serotonergic function in hippocampus might contribute to affective and behavioral symptoms in BPD.

MRI study of corpus callosum in patients with borderline personality disorder: a pilot study.

This pilot study examined the integrity of the corpus callosum in a sample of patients with borderline personality disorder (BPD), as abnormalities in inter-hemispheric communication could possibly be involved in illness pathophysiology. We utilized magnetic resonance imaging (MRI) signal intensity (SI) and morphometric measures. Ten BPD and 20 healthy control subjects were assessed for current and past Axis I and Axis II comorbidities and histories of childhood abuse. Regional CC SI and areas were measured with semi-automated software from three-dimensional gradient echo imaging scans. Analysis of covariance was conducted to evaluate the results. No significant differences were observed between BPD and controls in the SI or area of any CC region. Abnormalities in interhemispheric connectivity do not appear necessary for the development of BPD. Further studies with larger samples are needed to confirm this preliminary finding.

Suicidal Behavior and Psychosocial Outcome in Borderline Personality Disorder at 8-Year Follow-Up.

We sought predictors of both suicidal behavior and psychosocial outcome in subjects with BPD followed for 8 years and asked if there was a relationship between these outcomes. One hundred twenty-three BPD subjects, recruited from inpatient (35.8%), outpatient (30.9%) and community (33.3%) sources, were assessed annually for known risk factors for suicidal behavior. Interval attempts were reported by 25 subjects (20.2%). Increased risk of suicide attempt was associated with negative affectivity, aggression, inpatient recruitment, hospitalizations, minority race, and frequent changes in employment. Decreased risk was associated with increased education. Poor psychosocial outcome was predicted by impulsivity, negative affectivity, and antisocial traits at baseline, and by comorbid MDD at 8-year follow-up. There was no significant relationship between poor psychosocial outcome at 8-year follow-up and risk of suicidal behavior. Predictors of suicidality include modifiable risk factors. Rehabilitation models are needed to address educational and vocational deficits associated with suicidality, especially among minorities.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC.

Impulsivity and aggression mediate regional brain responses in Borderline Personality Disorder: An fMRI study.

Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets. First-level contrasts modeled effects of negative emotional context. Second-level regression models used trait impulsivity, aggression and depressed mood as predictor variables of regional brain activations. In BPD, trait impulsivity was positively correlated with activation in the dorsal anterior cingulate cortex, orbital frontal cortex (OFC), basal ganglia (BG), and dorsolateral prefrontal cortex, with no areas of negative correlation. In contrast, aggression was negatively correlated with activation in OFC, hippocampus, and BG, with no areas of positive correlation. Depressed mood had a generally dampening effect on activations. Effects of trait impulsivity on healthy controls differed from effects in BPD, suggesting a disorder-specific response. Negative emotional context and trait impulsivity, but not aggression or depression, diminished task performance across both groups. Negative emotional context may interfere with cognitive functioning in BPD through interaction with the neurobiology of personality traits.

Gender differences in a fenfluramine-activated FDG PET study of borderline personality disorder.

Neuroimaging studies of impulsive-aggressive subjects with borderline personality disorder (BPD) demonstrate hypometabolism in areas of prefrontal and frontal cortex, and a blunted cortical metabolic response to challenge with serotonergic agonists. Neuroendocrine responses to serotonergic challenge are known to vary greatly by gender, and may be related to sex differences in expression of impulsive aggression. We conducted single-blind, placebo-controlled fenfluramine-activated positron emission tomography (PET) studies in impulsive male and female subjects with BPD to look for gender differences in cortical response. The sample comprised 22 BPD (15 female, 7 male) and 24 control subjects (10 female, 14 male) who received placebo on Day 1 and d,l-fenfluramine on Day 2 before PET neuroimaging. In response to placebo, female, but not male, controls had areas of increased uptake of fluorodeoxyglucose-F18 in prefrontal cortex compared with BPD subjects, with greatest uptake in the medial orbital frontal cortex, bilaterally. Male, but not female, BPD subjects, showed areas of increased glucose utilization compared with controls in large areas of parietal and occipital cortex, bilaterally. In response to fenfluramine (relative to placebo), significant decreases in glucose uptake were found in male, but not female, BPD subjects, centered in the left temporal lobe. Female, but not male, control subjects showed significantly decreased uptake in areas of right frontal and temporal cortex. Covarying for impulsive-aggression rendered nonsignificant the gender differences in responses to placebo or fenfluramine. Gender differences in serotonergic function may mediate differences in behavioral expression of impulsive aggression in subjects with BPD.

High-lethality status in patients with borderline personality disorder.

Recurrent suicidal behaviors in patients with Borderline Personality Disorder (BPD) are often considered communicative gestures; however, 10% complete suicide. This study seeks to identify risk factors for suicide within a BPD sample by comparing patients with High- and Low-Lethality attempts. BPD attempters (n = 113) were assessed on demographic, diagnostic, and personality variables: clinical symptoms, suicidal behaviors; childhood, family, and treatment histories; social adjustment; and recent life events. Forty-four High-Lethality attempters, defined by a score of 4 or more on Beck's Medical Lethality Scale, were compared to 69 Low-Lethality attempters. Discriminating variables were entered in a multivariate logistic regression model to define predictors of High-Lethality status. High-Lethality attempters were older, with children, less education, and lower socioeconomic class (SES) than Low-Lethality attempters. They were more likely to have Major Depressive Disorder (MDD), co-morbid Antisocial Personality Disorder (ASPD), and family histories of substance abuse. They reported greater intent to die, more lifetime attempts, hospitalizations, and time in the hospital. High-Lethality status was best predicted by low SES, co-morbid ASPD, extensive treatment histories, and greater intent to die. These characteristics resemble profiles of patients who complete suicide, are not specific for BPD, and do not include impulsivity, aggression, or severity of BPD criteria.

Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence.

Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and the basal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic abnormalities. Task demands exert a differential effect on the cognitive response to negative emotion in BPD compared with control subjects.

Anatomical MRI study of borderline personality disorder patients.

Hippocampal volume reduction has been reported in patients with borderline personality disorder (BPD), and is hypothesized to be associated with traumatic childhood experiences. We extended this investigation to explore additional brain regions and other potential clinical correlates of structural brain changes in BPD. Ten unmedicated BPD subjects and 20 healthy controls were assessed for current and past Axis I and II comorbidities and histories of childhood abuse. All had magnetic resonance imaging (MRI) studies with a 1.5 T GE Signa Imaging System, performing three-dimensional-gradient echo imaging (SPGR) with the following parameters: TR=25 ms, TE=5 ms, and slice-thickness=1.5 mm. Compared with healthy controls, BPD subjects had significantly smaller right and left hippocampal volumes, most marked in subjects with childhood abuse, and significantly increased right and left putamen volumes, especially in subjects with substance use disorders. No significant differences between groups were found for caudate, amygdala, temporal lobes, dorsolateral prefrontal cortex and total brain volumes. This study replicated prior findings of diminished hippocampal volumes in subjects with BPD. Also, increased putamen volumes were found in BPD, a finding that has not been previously reported. Early traumatic experiences may play a role in hippocampal atrophy, whereas substance use disorders may contribute to putamen enlargement.

Impulsivity, gender, and response to fenfluramine challenge in borderline personality disorder.

Behavioral impulsivity in borderline personality disorder (BPD) is associated with indices of diminished central serotonergic function, independent of suicidal behavior, depression or alcohol use disorder. Many of these studies have been conducted among males in specialized settings. Studies of BPD females, who constitute the majority of BPD patients, are generally conducted in community settings and report inconsistent findings. We studied gender differences in behavioral impulsivity and the prolactin response to D,L-fenfluramine (FEN) in BPD subjects in a community setting. A FEN challenge study was conducted with 64 BPD subjects (20 male, 44 female), and 57 controls (36 male, 21 female). Axis I and II disorders, including BPD, and suicidal histories were assessed by structured interviews. Controls were free of Axis I and II disorders. Impulsivity and aggression were assessed by the Buss-Durkee Hostility Inventory, Barratt Impulsiveness Scale, Minnesota Multiphasic Personality Inventory-Psychopathic Deviate subscale, and the Brown-Goodwin Lifetime History of Aggression. Male, but not female, BPD subjects had significantly diminished prolactin responses compared to controls. Impulsivity and aggression each predicted prolactin responses. A significant effect of BPD diagnosis on prolactin response was eliminated when impulsivity was co-varied. Impulsivity and aggression were inversely related to delta-prolactin and peak-prolactin responses among male but not female subjects. Gender differences in central serotonergic function may contribute to variations in impulsivity in BPD.

Impulsivity and prefrontal hypometabolism in borderline personality disorder.

Prefrontal hypoperfusion and decreased glucose uptake in the prefrontal cortex (PFC) are found in violent criminal offenders, murderers and aggressive psychiatric patients. These abnormalities may be independent of diagnosis and associated with impulsive-aggression as a personality trait. Impulsive-aggression is a clinical characteristic of borderline personality disorder (BPD) where it is associated with assaultive and suicidal behaviors. We conducted FDG-PET studies in 13 non-depressed, impulsive female subjects with BPD and 9 healthy controls to look for abnormalities in glucose metabolism in areas of the PFC associated with regulation of impulsive behavior. Statistical Parametric Mapping-99 (SPM99) was used to analyze the PET data with Hamilton depression scores as covariate. Significant reductions in FDG uptake in BPD subjects relative to healthy controls were found bilaterally in medial orbital frontal cortex, including Brodmann's areas 9, 10 and 11. There were no significant areas of increased uptake in BPD subjects compared to control subjects. Covarying for measures of impulsivity or impulsive-aggression rendered insignificant the differences between groups. Decreased glucose uptake in medial orbital frontal cortex may be associated with diminished regulation of impulsive behavior in BPD.