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OBJECTIVE: Suicidal behavior is highly prevalent in borderline personality disorder and major depressive episode, although the characteristics of suicide attempts in the two disorders are believed to differ. Comorbidity of borderline personality disorder and major depressive episode may obscure characteristics of suicide attempts that are uniquely related to the psychopathology of each disorder. We compared suicidal behavior in patients with borderline personality disorder, major depressive episode, and borderline personality disorder plus major depressive episode to determine whether characteristics of suicide attempts differed between groups and if aspects of core psychopathology predicted specific attempt characteristics. METHOD: Eighty-one inpatients with borderline personality disorder, including 49 patients with borderline personality disorder plus major depressive episode, were compared to 77 inpatients with major depressive episode alone on measures of depressed mood, hopelessness, impulsive aggression, and suicidal behavior, including lifetime number of attempts, degree of lethal intent, objective planning, medical damage, and degree of violence of suicide methods. RESULTS: No significant differences were found in the characteristics of suicide attempts between patients with borderline personality disorder and those with major depressive episode. However, patients with both disorders had the greatest number of suicide attempts and the highest level of objective planning. An increase in either impulsive aggression or hopelessness or a diagnosis of borderline personality disorder predicted a greater number of attempts. Hopelessness predicted lethal intent in all three groups and predicted objective planning in the group with both disorders. Medical damage resulting from the most serious lifetime suicide attempt was predicted by number of attempts. CONCLUSIONS: Comorbidity of borderline personality disorder with major depressive episode increases the number and seriousness of suicide attempts. Hopelessness and impulsive aggression independently increase the risk of suicidal behavior in patients with borderline personality disorder and in patients with major depressive episode. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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.

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., (Copyright © 2019. Published by Elsevier B.V.)

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.

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.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., Competing Interests: None., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Impulsivity and aggressiveness are personality traits associated with a vulnerability to suicidal behavior. Behavioral expression of these traits differs by gender and has been related to central serotonergic function. We assessed the relationships between serotonin-2A receptor function, gender, and personality traits in borderline personality disorder (BPD), a disorder characterized by impulsive-aggression and recurrent suicidal behavior. Participants, who included 33 BPD patients and 27 healthy controls (HC), were assessed for Axis I and II disorders with the Structured Clinical Interview for DSM-IV and the International Personality Disorders Examination, and with the Diagnostic Interview for Borderline Patients-Revised for BPD. Depressed mood, impulsivity, aggression, and temperament were assessed with standardized measures. Positron emission tomography with [(18)F]altanserin as ligand and arterial blood sampling was used to determine the binding potentials (BPND) of serotonin-2A receptors in 11 regions of interest. Data were analyzed using Logan graphical analysis, controlling for age and non-specific binding. Among BPD subjects, aggression, Cluster B co-morbidity, antisocial PD, and childhood abuse were each related to altanserin binding. BPND values predicted impulsivity and aggression in BPD females (but not BPD males), and in HC males (but not HC females.) Altanserin binding was greater in BPD females than males in every contrast, but it did not discriminate suicide attempters from non-attempters. Region-specific differences in serotonin-2A receptor binding related to diagnosis and gender predicted clinical expression of aggression and impulsivity. Vulnerability to suicidal behavior in BPD may be related to serotonin-2A binding through expression of personality risk factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Course and outcome of Borderline Personality Disorder (BPD) are favorable for the vast majority of patients; however, up to 10% die by suicide. This discrepancy begs the question of whether there is a high lethality subtype in BPD, defined by recurrent suicidal behavior and increasing attempt lethality over time. In a prospective, longitudinal study, we sought predictors of high lethality among repeat attempters, and defined clinical subtypes by applying trajectory analysis to consecutive lethality scores. Criteria-defined subjects with BPD were assessed using standardized instruments and followed longitudinally. Suicidal behavior was assessed on the Columbia Suicide History, Lethality Rating Scale, and Suicide Intent Scale. Variables discriminating single and repeat attempters were entered into logistic regression models to define predictors of high and low lethality attempts. Trajectory analysis using three attempt and five attempt models identified discrete patterns of Lethality Rating Scale scores. A high lethality trajectory was associated with inpatient recruitment, and poor psychosocial function, a low lethality trajectory with greater Negativism, Substance Use Disorders, Histrionic and/or Narcissistic PD co-morbidity. Illness severity, older age, and poor psychosocial function are characteristics of a poor prognosis subtype related to suicidal behavior.

Objective: Recurrent suicidal behavior is a defining characteristic of borderline personality disorder. Although most patients achieve remission of suicidal behavior over time, as many as 10% die by suicide, raising the question of whether there is a high-risk suicidal subtype. The authors conducted a longitudinal study of suicidal behavior in borderline personality disorder patients to identify prospective predictors of suicide attempts and to characterize those patients at highest risk for suicide completion., Method: Demographic and diagnostic characteristics and clinical and psychosocial risk factors assessed at baseline were examined for predictive association with medically significant suicide attempts using Cox proportional hazards models. The authors defined prospective predictors for participants who completed 6 or more years in the study and compared the data to those of earlier intervals., Results: Among 90 participants, 25 (27.8%) made at least one suicide attempt in the interval, and most attempts occurred in the first 2 years. The risk of suicide attempt was increased by low socioeconomic status, poor psychosocial adjustment, family history of suicide, previous psychiatric hospitalization, and absence of any outpatient treatment before the attempt. Higher global functioning scores at baseline decreased this risk., Conclusions: Risk factors predictive of suicide attempt change over time. Acute stressors such as major depressive disorder were predictive only in the short term (12 months), while poor psychosocial functioning had persistent and long-term effects on suicide risk. Half of borderline patients have poor psychosocial outcomes despite symptomatic improvement. A social and vocational rehabilitation model of treatment is needed to decrease suicide risk and optimize long-term outcomes.

Background: Structural brain abnormalities have been demonstrated in subjects with BPD in prefrontal and fronto-limbic regions involved in the regulation of emotion and impulsive behavior, executive cognitive function and episodic memory. Impairment in these cognitive functions is associated with increased vulnerability to suicidal behavior. We compared BPD suicide attempters and non-attempters, high and low lethality attempters to healthy controls to identify neural circuits associated with suicidal behavior in BPD., Methods: Structural MRI scans were obtained on 68 BPD subjects (16 male, 52 female), defined by IPDE and DIB/R criteria, and 52 healthy controls (HC: 28 male, 24 female). Groups were compared by diagnosis, attempt status, and attempt lethality. ROIs were defined for areas reported to have structural or metabolic abnormalities in BPD, and included: mid-inf. orbitofrontal cortex, mid-sup temporal cortex, anterior cingulate, insula, hippocampus, amygdala, fusiform, lingual and parahippocampal gyri. Data were analyzed using optimized voxel-based morphometry implemented with DARTEL in SPM5, co-varied for age and gender, corrected for cluster extent (p < .001)., Results: Compared to HC, BPD attempters had significantly diminished gray matter concentrations in 8 of 9 ROIs, non-attempters in 5 of 9 ROIs. Within the BPD sample, attempters had diminished gray matter in Lt. insula compared to non-attempters. High lethality attempters had significant decreases in Rt. mid-sup. temporal gyrus, Rt. mid-inf. orbitofrontal gyrus, Rt. insular cortex, Lt. fusiform gyrus, Lt. lingual gyrus and Rt. parahippocampal gyrus compared to low lethality attempters., Conclusions: Specific structural abnormalities discriminate BPD attempters from non-attempters and high from low lethality attempters., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A childhood history of sexual or physical abuse is highly prevalent in borderline personality disorder (BPD) and is associated with self-destructive behavior in clinical and nonclinical samples. Viewing BPD as a "high risk" disorder, we asked if childhood abuse was a risk factor for adult suicidal behavior or if it was related to other known risk factors for suicide in BPD. A semistructured Abuse History was obtained in 61 criteria-defined BPD patients, who were characterized by structured interviews and self-reports for Axis I disorders, Suicide History, BPD severity, hopelessness, impulsivity, impulsive-aggression, and antisocial traits. Occurrence and severity of childhood sexual abuse, but not physical abuse, predicted adult suicidal behavior independent of other known risk factors. The odds of a sexually abused patient attempting suicide in adulthood was over 10 times that of a patient who was never sexually abused. Given a history of childhood sexual abuse, the risk of adult suicidal behavior in BPD was increased by antisocial traits, severity of BPD, hopelessness, or comorbid major depressive episode (MDE).

This study investigated the impact of recent life events and social adjustment on suicide attempter status in 34 patients with major depression, 24 patients with borderline personality disorder, and 22 patients with co-morbid major depression and borderline personality disorder. Suicide attempters reported more recent life events and scored lower on a measure of social adjustment in their families and overall social adjustment, compared with non-attempters. Borderline disordered and borderline or depressed patients were more likely to have attempted suicide than patients with major depression only. Recent life events did not predict attempter status. Lower social adjustment in the immediate family and lower overall social adjustment were predictive of suicide attempter classification, regardless of diagnosis. Borderline disordered patients low on overall social adjustment were over 16 times more likely to have attempted suicide than patients diagnosed with major depression only. Recent life events may elevate suicide risk in groups already at high risk for suicide completion, whereas high levels of social adjustment may be protective against stress-related suicidal behavior.

Background: Alcohol use disorders (AUDs) among adolescents are associated with a high prevalence of conduct disorder (CD), much as type II alcoholism in adults is associated with impulsive-aggressive behavior and antisocial personality traits. Adults with impulsive personality disorders and AUD demonstrate diminished central serotonergic responsiveness to serotonergic agonists. Dysregulation of central serotonergic function may contribute to a vulnerability to impulsive-aggressive behavior, CD, and AUD. We studied older adolescents, both male and female, to examine the relationships between sex, dispositional impulsivity, aggressivity, CD, and responsiveness to serotonergic challenge with d,l fenfluramine (FEN) early in the development of AUD., Methods: Thirty-six adolescents between the ages of 16 and 21 years were assessed for DSM-IV AUD and other Axis I disorders by using the Psychoactive Substance Use Disorders section of the Structured Clinical Interview for DSM III-R, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, and CD interviews. Impulsivity and aggressivity were assessed by the Barratt Impulsiveness Scale, Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Eysenck Impulsiveness Questionnaire, Youth Self Report, and Multidimensional Personality Questionnaires. FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels., Results: Eighteen adolescents (12 male, 6 female) with AUD scored significantly higher on all measures of impulsivity and aggressivity compared with 18 healthy controls (12 male, 6 female). There were no significant differences between groups in peak prolactin or cortisol responses (minus baseline), or area-under-the-curve determinations (AUC); however, 9 subjects with AUD and comorbid CD had significantly elevated cortisol AUC levels compared with subjects with AUD and no CD or with normal controls. In the total sample, cortisol AUC was associated positively with measures of aggression., Conclusions: Adolescents with early-onset AUD are characterized by impulsivity and aggressivity compared with healthy peers but do not demonstrate the diminished prolactin or cortisol responses to FEN characteristic of adult alcoholics with impulsive-aggression.

Objective: Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects., Method: Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness., Results: Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups., Conclusions: In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.

Background: Impulsive aggression in patients with personality disorders is associated with diminished levels of cerebrospinal fluid (CSF) 5-HIAA, blunted neuroendocrine responses to serotonergic agonists, and decreased glucose utilization in the prefrontal cortex. We tested the hypothesis that impulsive aggression in borderline personality disorder (BPD) may be associated with diminished serotonergic regulation in the prefrontal cortex, using positron-emission tomography (PET) neuroimaging during pharmacologic challenge with d,l fenfluramine (FEN)., Methods: A 2-day, single-blind, placebo-controlled FEN challenge study was conducted in five patients with BPD (and no Axis I MDD) and eight healthy control participants. On Day 1, 4 mCi [(18)F]-fluorodeoxyglucose (FDG) was injected 3 hours after ingestion of placebo; on Day 2, FDG was injected 3 hours after ingestion of.8 mg/kg to 60 mg of d,l fenfluramine. After 30 min, a 45-min emission scan was acquired on the Siemans/CTI 951r/31 scanner. PET data were aligned to MR images and analyzed by Statistical Parametric Mapping (SPM96)., Results: In response to placebo, uptake of FDG was greater in control participants than patients in large areas of the prefrontal cortex including medial and orbital regions bilaterally (BA 10-11), left superior temporal gyrus, and right insular cortex. There were no areas in which patients had greater relative regional uptake than control participants. In response to FEN, relative regional uptake of FDG (relative to placebo) was greater in control participants compared to patients in medial and orbital regions of right prefrontal cortex (BA 10), left middle and superior temporal gyri (BA 22-23), left parietal lobe (BA 40), and left caudate body., Conclusions: Patients with BPD have diminished response to serotonergic stimulation in areas of prefrontal cortex associated with regulation of impulsive behavior.

Pharmacotherapy for patients with borderline personality disorder is directed against the psychobiology of cognitive-perceptual, affective, and impulsive-behavioral symptoms. A symptom-specific method using current empiric evidence for drug efficacy in each symptom domain is proposed. Drugs in each medication class have some potential utility against specific symptoms in patients with borderline personality disorder.

A pharmacological approach to treating patients with personality disorders (PD) is based on evidence that some dimensions of personality are mediated by variations in neurotransmitter physiology and are responsive to medication effects. Target symptoms for pharmacotherapy in the PD patient are derived from expressions of cognitive-perceptual, affective, and impulsive-behavioral dysregulation of central neurotransmitter functions. Pharmacotherapy is directed at state symptoms during periods of acute decompensation and at trait vulnerabilities, which represent the diathesis to future episodes. A basic assumption of this approach is that neurotransmitter biology transcends Axis I and Axis II definitions and that closely related symptoms may share a common pathophysiology, independent of categorical definition. A common pathophysiology implies the possibility of shared responsiveness to medication. Using a dimensional definition of symptom domains, the author has developed treatment algorithms for cognitive-perceptual symptoms, affective dysregulation, and impulsive-behavioral dyscontrol in personality disorder patients.

Objective: This study identified potential risk factors for suicidal behavior in patients with borderline personality disorder defined by the Diagnostic Interview for Borderline Patients and by DSM-III-R criteria for patients who did and did not attempt suicide., Method: Histories of suicide attempts and attempt characteristics were obtained by Schedule for Affective Disorders and Schizophrenia interviews from 84 patients with borderline personality disorder and were related to severity of borderline pathology, diagnostic comorbidity, and state and trait symptoms., Results: There were 61 patients with a lifetime history of suicide attempts (72.6%), with an average of 3.39 (SD = 2.87) attempts per patient. Attempters were significantly older than nonattempters, with more impulse actions, antisocial personality disorder comorbidity, and state depression. State depression was significantly less severe in patients who had attempted suicide in the present episode (or past year) than in patients who had attempted suicide only in the past. A comorbid diagnosis of major depression, alcoholism, or drug use disorder did not distinguish attempters from nonattempters. Suicide attempt in the present episode was best predicted by the number of prior lifetime attempts. A highly serious intent to commit suicide was predicted by the number of lifetime attempts and subjective depression, while a low intent was predicted by a mixed subtype of borderline personality disorder plus schizotypal personality disorder and paranoid ideation. A high degree of medical lethality was predicted by number of lifetime attempts, older age, and hysteroid dysphoria, while low lethality attempts were associated with high degrees of anger., Conclusions: Risk factors for suicidal behavior in patients with borderline personality disorder include older age, prior suicide attempts, antisocial personality, impulsive actions, and depressive moods but not comorbid affective disorder, alcoholism, or drug use disorders.

Psychotropic medication is used extensively in the borderline patient in an effort to treat the cognitive, affective, impulsive-behavioral and anxious-fearful symptoms which comprise the state symptoms and trait vulnerabilities of BPD. This paper reviews the efficacy of neuroleptics, antidepressants (TCA, MAOI and SSRI), lithium carbonate, carbamazepine and benzodiazepines against these 4 symptom domains. There is currently no single drug treatment of choice in BPD. Current research supports acute treatment. Maintenance trials are generally lacking or show limited efficacy. A dimensional approach is recommended for clinical practice and future research trials, targeting specific symptom domains with selective medication. Pharmacotherapy should be viewed as a useful adjunct to psychotherapy in the long-term treatment of the borderline patient.

Objective: The aim of this study was to assess the effectiveness of low-dose neuroleptic medication and monoamine oxidase inhibitor (MAOI) antidepressant medication in continuation pharmacotherapy of patients with borderline personality disorder., Method: The authors conducted a double-blind, placebo-controlled study comparing continuation therapy with a neuroleptic (up to 6 mg/day of haloperidol), an MAOI antidepressant (up to 90 mg/day of phenelzine), and placebo in 14 men and 40 women with borderline personality disorder. Continuation medication trials lasted 16 weeks, following 5 weeks of acute therapy., Results: Continuing haloperidol demonstrated efficacy only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the patients who received haloperidol than in those who received phenelzine and those who received placebo. The dropout rate during the first 8 weeks of the continuation study was significantly higher for the patients receiving haloperidol (64%) than for those receiving placebo (28%). Continued phenelzine demonstrated only modest efficacy for the treatment of depression and irritability. An activating effect of phenelzine was shown on measures of excitement and reactivity., Conclusions: No evidence of efficacy was found for continuation therapy with haloperidol in the treatment of borderline personality disorder other than in the treatment of irritability. Little evidence of efficacy was found for continuation therapy with phenelzine for borderline personality disorder other than modest improvements in irritability and depressive symptoms. There is currently no clear pharmacological treatment of choice for the continuation therapy of borderline personality disorder.

Objective: To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response., Design: Randomized, double-blind, placebo-controlled trial., Setting: Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area., Patients: One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials., Interventions: Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations., Main Outcome Measures: Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index)., Results: Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic., Conclusions: Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

We report the first double-blind, placebo-controlled continuation study comparison of a neuroleptic (haloperidol < or = 6 mg), monoamine oxidase inhibitor (MAOI) antidepressant (phenelzine < or = 90 mg), and placebo in 54 patients with borderline personality disorder. Continuation medication trials of 16 weeks followed 5 weeks of acute therapy. Haloperidol continued to be effective beyond the acute phase only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the haloperidol group than in the phenelzine and placebo groups. The dropout rate during the first half (8 weeks) of the continuation study was significantly higher for the haloperidol group (64%) than for the placebo group (28%) (p < .05). Phenelzine demonstrated very modest efficacy beyond that noted in the acute phase for the treatment of depression and irritability. Phenelzine was shown to have an activating effect on measures of excitement and reactivity.

Borderline personality disorder is characterized by many of the symptoms associated with serotonin dysregulation, including affective lability, suicidal behaviors, and impulsive aggression. These provide an ideal clinical model for studying the treatment of these serious symptom presentations. The recent development of selective serotonin reuptake inhibitors such as fluoxetine makes it possible to study the role of serotonin in the etiology of affective and behavioral dyscontrol in borderline personality disorder. In this preliminary medication trial, 5 borderline personality disorder patients with severe symptoms resistant to phenelzine and neuroleptics were treated openly with fluoxetine 20 to 40 mg for 8 weeks, with weekly ratings of symptoms. The findings from this work suggested efficacy for fluoxetine in treating the depressive and impulsive symptoms of refractory patients with borderline personality disorder.

Depression in the borderline patient may present as a reactive mood state, an expression of character, or an independent comorbid affective disorder. The symptom picture is most often heterogeneous, "atypical," and chronic. Pharmacologic trials with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) produce modest improvement on a variety of symptoms, though not always on depression. Medication effects on depressed mood in borderline personality disorder (BPD) are independent of comorbid diagnoses of major depression, atypical depression, or hysteroid dysphoria. Residual symptoms are the rule. A literature review, including studies of comorbidity, longitudinal followup, family history, and laboratory and pharmacotherapy studies, suggests that the borderline patient has both a core biologic affective dysregulation and a pathologic personality organization. The combination of constitutional and psychodynamic etiologies for borderline pathology requires consideration of both pharmacotherapy and psychotherapy in any comprehensive treatment.

Borderline personality disorder (BPD) is defined by many of the symptoms associated with serotonin dysregulation, including affective lability, suicidal behaviors, and impulsive aggression, providing an ideal clinical model for studying the treatment of these serious disorders. The recent development of selective serotonin re-uptake inhibitors such as fluoxetine makes it possible to study the role of serotonin in the etiology of affective and behavioral dyscontrol in BPD. In this preliminary medication trial, 5 patients with BPD were treated openly with 20 mg to 40 mg of fluoxetine for 8 weeks, with weekly ratings of symptoms. The findings from this work suggested efficacy for fluoxetine in treating the depressive and impulsive symptoms of patients with BPD. The findings were mixed concerning the efficacy of fluoxetine in treating the hostility and psychotic symptoms of BPD. No evidence for effectiveness was found in the treatment of the anxiety, phobic anxiety, or interpersonal sensitivity of BPD.

The authors investigated the pharmacological treatment of delusional depression by assigning patients on a random double-blind basis to amitriptyline alone, perphenazine alone, or a combination of the two. Fourteen (78%) of the 18 patients assigned to amitriptyline plus perphenazine were responders, compared with seven (41%) of 17 patients treated with amitriptyline alone and three (19%) of the 16 patients treated with perphenazine alone. The combination of amitriptyline and perphenazine was clearly superior (p less than .01).

The authors report the final results of a 4-year study of amitriptyline and haloperidol in 90 symptomatic borderline inpatients. Medication trials were double-blind and placebo controlled and lasted 5 weeks. Haloperidol (4-16 mg/day) produced significant improvement over placebo in global functioning, depression, hostility, schizotypal symptoms, and impulsive behavior. Significant effects of amitriptyline (100-175 mg/day) were generally limited to measures of depression. Factor analysis identified three symptom change patterns: a global depression, hostile depression, and schizotypal symptom pattern. Medication effects favoring haloperidol were most prominent for hostile depression. Variables predicting favorable response to haloperidol included severity of schizotypal symptoms, hostility, and suspiciousness. Schizotypal symptoms and paranoia predicted poor outcome on both depression patterns with amitriptyline. Placebo effects were most prominent on acute state symptoms, with severe character traits predicting poor response.

Recent authors have hypothesized that cerebral dysfunction, as reflected in an abnormal EEG, may play an important role in the behavioral symptoms of patients with borderline personality disorder (BPD). Spectral analysis and amphetamine challenge testing are two promising methods for probing the clinical symptomatology of this disorder. In this study, we evaluated the relationship between clinical symptoms and computerized EEG spectral analysis in BPD patients both before and after amphetamine challenge. We found that mean frequency values on spectral analysis consistently correlated with anxiety levels in our patients, but did not correlate with a wide variety of other important symptoms, such as depression or transient psychosis. This result, coupled with our previous negative findings concerning EEG abnormalities in patients with BPD, casts doubt on the etiological relationship of cerebral dysrhythmias to the behavioral pathology of this disorder, but raises interesting questions concerning the relationship of anxiety and mean frequency.

The use of denial has been widely accepted as an adaptive and protective coping mechanism in the acute phase of myocardial infarction. Although instrumental in lowering anxiety and mortality in the acute phase of coronary care, the use of denial creates hazards for the patient in convalescence. These hazards, not well known to intensive care personnel but all too apparent to the liaison psychiatrist working in cardiovascular rehabilitation, include a high vulnerability to disruptive anxiety and even psychosis at times of transition from greater to lesser intensity nursing care and a maladaptive resistance to rehabilitation efforts in convalescence. Failure of denial under the stress of transition may produce a transient paranoid psychosis with a clear sensorium, a variant of Abram's "cardiac psychosis." Maintenance of the defense in convalescence leads to noncompliance with medical advice and rejection of rehabilitation efforts, increasing the risk of reinfarction. A case report is presented illustrating both hazards. Recommendations for management include early recognition, supportive psychotherapy, education and mobilization in the acute phase of coronary care. Cardiovascular conditioning and reshaping of risk factors follow in convalescence. The physical and psychological benefits of this approach are reviewed. The adaptive value of denial in coronary patients is challenged from the long-term perspective of rehabilitation.