Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences.

OBJECTIVES: many studies have reported a high degree of comorbidity between mood disorders, among which are bipolar disorders, and borderline personality disorder and some studies have suggested that these disorders are co-transmitted in families. However, few studies have compared personality traits between these disorders to determine whether there is a dimensional overlap between the two diagnoses. The aim of this study was to compare impulsivity, affective lability and intensity in patients with borderline personality and bipolar II disorder and in subjects with neither of these diagnoses. METHODS: patients with borderline personality but without bipolar disorder (n=29), patients with bipolar II disorder without borderline personality but with other personality disorders (n=14), patients with both borderline personality and bipolar II disorder (n=12), and patients with neither borderline personality nor bipolar disorder but other personality disorders (OPD; n=93) were assessed using the Affective Lability Scale (ALS), the Affect Intensity Measure (AIM), the Buss-Durkee Hostility Inventory (BDHI) and the Barratt Impulsiveness Scale (BIS-7B). RESULTS: borderline personality patients had significantly higher ALS total scores (P<0.05) and bipolar II patients tended to have higher ALS scores than patients with OPD (P<0.06). On one of the ALS subscales, the borderline patients displayed significant higher affective lability between euthymia and anger (P<0.002), whereas patients with bipolar II disorder displayed affective lability between euthymia and depression (P<0.04), or elation (P<0.01) or between depression and elation (P<0.01). A significant interaction between borderline personality and bipolar II disorder was observed for lability between anxiety and depression (P<0.01) with the ALS. High scores for impulsiveness (BISTOT, P<0.001) and hostility (BDHI, P<0.05) were obtained for borderline personality patients only and no significant interactions between diagnoses were observed. Only borderline personality patients tended to have higher affective intensity (AIM, P<0.07). CONCLUSIONS: borderline personality disorder and bipolar II disorder appear to involve affective lability, which may account for the efficacy of mood stabilizers treatments in both disorders. However, our results suggest that borderline personality disorder cannot be viewed as an attenuated group of affective disorders.

Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia.

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.

Are the interpersonal and identity disturbances in the borderline personality disorder criteria linked to the traits of affective instability and impulsivity?

This study examines the degree to which two putative biologically influenced personality traits, affective instability and impulsive aggression, are associated with some of the interpersonal and intrapsychic disturbances of borderline personality disorder (BPD) and with choice of defense mechanism. In a sample of 152 personality disorder patients, affective instability and impulsive aggression were measured. Defense mechanisms were assessed in 140 of these patients using the Defensive Style Questionnaire (DSQ). The correlations between the traits of affective instability and impulsive aggression and the eight DSM-III-R criteria for borderline personality disorder and 20 DSQ defenses were examined. Affective instability was significantly correlated with the DSM-III-R criteria of identity disturbance, chronic emptiness or boredom, inappropriate anger, suicidality, and the affective instability criteria. It also was associated with the defenses of splitting, projection, acting out, passive aggression, undoing, and autistic fantasy. Impulsive aggression was related to unstable interpersonal relationships, inappropriate anger and impulsiveness and with the defense of acting out. It was negatively correlated with the defenses of suppression and reaction formation. A number of the interpersonal and experiential disturbances and defense mechanisms that are features of BPD are associated with the traits of affective instability and impulsive aggression among patients with personality disorders.

Suicide, impulsive aggression, and HTR1B genotype.

BACKGROUND: Suicidality and impulsive aggression are partially heritable, and postmortem brain studies suggest that abnormalities in serotonin 1B may be associated with suicide. Studies of serotonin 1B "knockout" mice show an increase in aggressive behavior relative to wild-type mice. METHODS: We assessed the relationship between genotype at the HTR1B locus and both suicide history and impulsive aggression in personality disorders. RESULTS: The "G" allele of a polymorphic gene at the HTR1B locus was associated with a history of suicide attempts in white patients with personality disorders [chi(2)(1) = 9.3, p =.01, n = 90]. No relationship was found between HTR1B genotype and self-reported impulsive aggression. CONCLUSIONS: This preliminary finding suggests that allelic variability at the HTR1B locus may be associated with the susceptibility to suicide attempts in patients with personality disorders.

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia.

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.

Physostigmine and cognition in schizotypal personality disorder.

There is evidence that reduced cholinergic activity may play a role in the pathophysiology of cognitive impairment in the schizophrenia spectrum. We tested the effects of physostigmine, an anticholinesterase inhibitor, on visuospatial working memory as evaluated by the Dot test, and on verbal learning and recall as measured by a serial learning task in patients with schizotypal personality disorder. Physostigmine tended to improve the Dot test, but not serial verbal learning performance in these patients.

Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder.

BACKGROUND: The importance of neuronal interactions in development, the cortical dependence of many thalamic nuclei, and the phenomenon of transsynaptic degeneration suggest possible abnormalities in thalamic nuclei with connections to other brain regions implicated in schizophrenia. Because frontal and temporal lobe volumes are diminished in schizophrenia, volume loss could characterize their primary thalamic relay nuclei (mediodorsal nucleus [MDN] and pulvinar). METHODS: Tracers delineated the thalamus, MDN, and pulvinar on contiguous 1.2-mm magnetic resonance images in 12 schizophrenic patients, 12 with schizotypal personality disorder (SPD), and 12 normal control subjects. The MDN and pulvinar were rendered visible by means of a Sobel intensity-gradient filter. RESULTS: Pixel overlap for delineation of all structures by independent tracers was at least 80%; intraclass correlations were r = 0.78 for MDN and r = 0.83 for pulvinar. Pulvinar volume was smaller in schizophrenic (1.22 +/- 0.24 cm(3)) and SPD (1.20 +/- 0.23 cm(3)) patients than controls (1.37 +/- 0.25 cm(3)). Differences for MDN were not statistically significant; however, when expressed as percentage of total brain volume, pulvinar and MDN together were reduced in SPD (0.14%) and schizophrenic (0.15%) patients vs controls (0.16%). Reductions were more prominent in the left hemisphere, with MDN reduced only in the schizophrenic group, and pulvinar in both patient groups. Total thalamic volume did not differ among the 3 groups. CONCLUSIONS: Measurement of MDN and pulvinar in magnetic resonance images is feasible and reproducible. Schizophrenic and SPD patients have volume reduction in the pulvinar, but only schizophrenic patients show reduction relative to brain volume in MDN.

Visuospatial working memory in schizotypal personality disorder patients.

BACKGROUND: Cognitive processing deficits have been identified as an abnormality that schizotypal personality disorder (SPD) individuals share with schizophrenic patients. It has been hypothesized that impaired working memory may be a critical component of several of the more complex cognitive deficits found in schizophrenia spectrum patients. METHOD: 18 DSM-III-R SPD patients, and 17 normal comparison subjects were compared on a pen and paper visuospatial working memory task. Moreover, we identified a second psychiatric comparison group comprised of nine patients with other, non-odd cluster personality disorder diagnoses who met no more than one of the SPD criteria and were also tested on the same task. Each person was given 14 immediate recall trials and 10 trials using a 10 s delay. RESULTS: SPD patients performed significantly worse than normal control subjects on the working memory task. SPD patients also performed significantly worse compared to the non-schizophrenia-related personality disorder psychiatric comparison group. CONCLUSIONS: Like schizophrenic patients, SPD patients demonstrate working memory impairment compared to normal controls. This impairment may be specific to the schizophrenia-related personality disorders.

Effects of amphetamine on visuospatial working memory performance in schizophrenia spectrum personality disorder.

Our objective was to determine if amphetamine improves visuospatial working memory, which is impaired in the schizophrenia spectrum and may be modulated by dopamine in prefrontal cortex. To this end, oral amphetamine (30 mg) was administered to 12 patients with schizophrenia spectrum personality disorders and 13 patients with other, nonschizophrenia-related personality disorders. Visuospatial working memory was assessed using the Dot test; a test in which subjects are asked to memorize and reproduce the position of a dot on a sheet of paper. Patients with schizophrenia spectrum personality disorders performed significantly worse than the comparison group in the placebo condition and showed significantly greater improvement after amphetamine, as compared to a nonschizophrenia-related personality disorder comparison group. Patients with greatest impairment at baseline improved most. Amphetamine tended to improve negative symptoms; whereas, positive symptoms remained unchanged. Amphetamine may improve visuospatial working memory in schizophrenia spectrum patients.

Serum cholesterol and impulsivity in personality disorders.

Decreased serum cholesterol has been associated with impulsive aggressive behaviors. This study was designed to explore the relationship between serum cholesterol levels and measures of impulsive aggression in personality disordered patients. Forty-two personality disordered patients (14 borderline personality disorder, 28 other personality disorders) were included. Fasting serum cholesterol was measured by standard enzymatic assay. An ANOVA was performed with factors of gender and diagnosis, looking at two-way interactions between the factors and serum cholesterol. Patients with borderline personality disorder were found to have significantly lower serum cholesterol than non-borderline personality disorders. A significant interaction effect was also seen between gender and diagnosis with the male patients having lower cholesterol levels. This study suggests there may be a relationship between borderline personality disorder and low serum cholesterol.

d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography.

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that, may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

Serotonin and the prediction of response time to fluoxetine in patients with mild depression.

Serotonin (5-HT) dysregulation has been associated with major depressive disorder (MDD); a blunted prolactin (PRL) response to D,L-fenfluramine (FEN) has been associated with MDD. Pharmacologic manipulation of the serotonin system with a selective serotonin reuptake inhibitor (SSRI) is effective in the treatment of depression. However, the relationship between pre-treatment 5-HT activity and response to SSRIs is not well understood. This study investigated the relationship between 5-HT dysregulation and response to fluoxetine (FLU). Twenty patients with MDD entered a double-blind placebo-controlled trial of fluoxetine preceded by D,L-fenfluramine stimulation. Patients were assigned randomly to either FLU, 20 mg QD, or placebo (PLA) for an 11-week trial. No relationship was found between the PRL response to FEN and response to FLU. Among the seven responding to FLU, there was a significant negative correlation between PRL response and the time until sustained response to FLU (r = -0.93, P < 0.001, n = 7). Although preliminary, this study suggests that low baseline serotonin activity may be associated with a slower response to FLU in depression.

Relationship between depression and borderline personality disorder.

The frequent occurrence of depressive symptoms in patients with borderline personality disorder has generated considerable interest in the nature of the relationship between borderline personality disorder and the depressive disorders. Data from the perspectives of phenomenology, biology, family history, course of illness, comorbidity patterns, and treatment response have been brought to bear on the question. Reviews based on research available by 1985 and 1991, respectively, arrived at differing conclusions: (1) that both disorders shared common but non-specific sources, and (2) that the two disorders were unrelated but co-occurred because of the high prevalence of each. Since the time of these reviews, additional evidence has become available from a wider range of biological investigations, better controlled comorbidity studies, studies of the relationship of psychosocial stressors to the course of each disorder and neuroimaging studies. In reviewing the more recent findings, we propose the less parsimonious hypothesis that the disorders co-occur, both because they share some common biological features and because the psychosocial sequella of each can contribute to the development of the other.

Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study.

To assess the relationship between two phenotypes in an extremely well-characterized population of personality disorder patients-impulsive aggression and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype, TPH genotype (at an intronic polymorphic site) and prolactin response to fenfluramine were assessed in 40 Caucasian patients with personality disorder. Impulsive aggression was assessed by using the Buss-Durkee Hostility Inventory (BDHI). Twenty-one male patients with the "LL" genotype had higher BDHI scores than men with the "UL" or the "UU" genotype. No relationship between genotype and prolactin response to fenfluramine was found. It was concluded that impulsive-aggressive behavior in male personality disorder patients may be associated with the TPH genotype.

Depressive response to physostigmine challenge in borderline personality disorder patients.

The purpose of this study was to examine the relationship between mood and hormonal responses to cholinergic challenge with physostigmine in order to assess cholinergic system responsiveness in borderline personality disorder (BPD) patients, other non-BPD personality disorder patients, and normal controls. Thirty-four personality disorder patients, 10 of whom met criteria for BPD and 24 of whom met criteria for other, non-borderline, personality disorders, and 11 normal controls participated in a double blind, placebo controlled physostigmine challenge paradigm. The Profile of Mood States depression subscale (POMS-D) self report measure was obtained at baseline and following the physostigmine or placebo infusions. A repeated measures ANOVA of POMS-D scores in placebo and drug conditions indicated a significantly greater depressive response in the total cohort of personality disorder patients than in the normal comparison group (p < 0.05). However, the depressive response to physostigmine was significantly greater in BPD patients, but not other personality disorder patients, compared to normal controls (p < 0.05). There was a correlation between the peak placebo-corrected depressive response to physostigmine and a group of BPD traits related to affective instability but not a group of BPD traits related to impulsivity. There was no correlation in any group between mood response to physostigmine and changes in plasma cortisol, prolactin, or growth hormone, or to nausea or other side effects following physostigmine infusion. These data suggest that there is an association between BPD and acute depressive responses to physostigmine challenge, and that the cholinergic system may be involved in the regulation of affect in Axis II disorders.

Assessing axis II disorders by informant interview.

Although much of personality disorder research depends on diagnostic data obtained directly from patients, this approach has rarely been compared to interviews with knowledgeable informants. The purpose of this study was to determine the diagnostic agreement between these two assessment methods, as well as their relative contribution to the formulation of consensus diagnoses. Sixty-two psychiatric patients were assessed directly with the Structured Interview for DSM-III Personality Disorders (SIDP), and were asked to nominate an informant--either a family member or friend--to provide information about the patient in an interview with the same instrument. Informant interviews were conducted blind to patient-based information whenever feasible, and diagnostic consensus was achieved by an independent review of all available data by a senior clinician. Diagnostic agreement between patient-based and informant-based personality disorder interview was poor, confirming the findings of two previous studies. Information obtained from patients tended to be given greater weight in formulating consensus diagnoses than information provided by informants. However, about one quarter of diagnostic disagreements were resolved in favor of informant-based information. In contrast to a previous study, the inclusion of informant information did not appear to reveal greater psychopathology in patients. We conclude that supplementing direct patient interview with data provided by a knowledgeable informant appears to enhance the resolution of some personality disorder diagnoses. The utility of informant interviews may depend on an analysis of the costs and benefits of this additional degree of descriptive refinement.

Attentional functioning in schizotypal personality disorder.

OBJECTIVE: Previous research has shown biological, phenomenological, and cognitive similarities between schizophrenic patients and individuals with schizophrenia-related personality disorders and features. Evidence further suggests that of these common dysfunctions, abnormal attention is one of the most promising indicators of a biological susceptibility to schizophrenia-related disorders. Although attentional dysfunctions have been reliably detected in schizophrenic patients as well as in a variety of populations at risk for schizophrenia, few studies have investigated attention in clinical patients with schizotypal personality disorder. In this study, the extent of attentional impairment was assessed in subjects with schizotypal personality disorder, normal comparison subjects, patients with other personality disorders, and schizophrenic patients. METHOD: Thirty subjects with schizotypal personality disorder, 35 subjects with other personality disorders (i.e., clinic patients with non-odd cluster personality disorders), 36 subjects with schizophrenia, and 20 comparison subjects who did not meet criteria for any axis I or axis II disorder participated in this study. All subjects were diagnosed according to DSM-III criteria. Attention was assessed by using the Continuous Performance Test, Identical Pairs Version. RESULTS: Analyses indicated that subjects with schizotypal personality disorder, like schizophrenic subjects, performed significantly worse than comparison subjects on both the verbal and spatial tasks of the Continuous Performance Test, Identical Pairs Version. In contrast, patients with other personality disorders performed similarly to comparison subjects across conditions. CONCLUSIONS: These results suggest that patients with schizotypal personality disorder are impaired in their attentional functioning relative to normal comparison subjects and that they display deficits that are similar to the pattern characterizing schizophrenic patients.

Serotonergic function and self-injurious behavior in personality disorder patients.

Self-directed aggression, whether in the form of non-suicidal self-mutilation or suicidal behavior, is a prominent feature of personality disorders. We hypothesized that self-injurious behavior, like suicidal behavior, represents a form of self-directed aggression, and may, like suicidal behavior and impulsive aggression, be associated with a decrease in central serotonin function in personality disorder patients. Ninety-seven patients with DSM-III personality disorder underwent D,L-fenfluramine challenge as an assessment of serotonergic activity. Patients with a history of self-mutilation or suicide had blunted prolactin and cortisol responses to D,L-fenfluramine compared to those with neither, and those with both had the most blunted responses to fenfluramine. These data raise the possibility that the central 5-HT abnormality, previously associated with suicidal behavior, may be associated with self-directed violence and not necessarily specifically with suicidal intent.

Impulsivity and serotonergic function in compulsive personality disorder.

This study compared serotonergic function, as assessed by prolactin response to fenfluramine, in males with compulsive personality disorder, males with noncompulsive personality disorders, and normal control subjects. The two patient groups did not differ in age, depression status, suicide history, or comorbid borderline personality disorder. However, compulsive personality disorder patients had significantly greater impulsive aggressive scores than the noncompulsive patients and significantly blunted prolactin responses compared with the non-compulsive patients and normal control subjects. In the combined patient group, total compulsive personality disorder traits correlated positively with impulsive aggression score and inversely with prolactin response. These results support the hypothesis that impulsive and compulsive symptoms do not simply lie at opposite ends of a phenomenological and neurobiological spectrum, but rather have a complex intersection and may both correlate with serotonergic dysfunction.

D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder.

The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine-associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge.