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Borderline personality disorder (BPD) is characterized by greater intensity of reactions to unpleasant emotional cues and a slower-than-normal return of these responses to baseline. Habituation is defined as decreased response to repeated stimulation. Affect-modulated startle (AMS), a translational psychophysiological approach, is mediated by the amygdala and used to study emotion processing in both humans and animals. This is the first study to examine the specificity of habituation anomalies in BPD during passive emotional and neutral picture processing.A total of 90 participants were studied: patients with BPD (n = 35), patients with schizotypal personality disorder (n = 26; included as a psychopathological comparison group), and healthy control subjects (n = 29). Participants received rigorous clinical assessments, and patients were unmedicated. AMS was examined during a series of intermixed unpleasant, neutral, and pleasant pictures.Compared with the other groups, patients with BPD showed greater overall AMS during unpleasant pictures and prolonged habituation of startle amplitude during unpleasant pictures from early to later trials. The groups did not differ in AMS during neutral or pleasant pictures or self-reported picture valence. Among the patients with BPD, prolonged habituation to unpleasant pictures was associated with greater symptom severity and suicidal/self-harming behavior.These findings 1) indicate that abnormal processing of and habituation to unpleasant pictures is observed in BPD but not schizotypal personality disorder, suggesting that these deficits are not simply characteristics of personality disorders in general; 2) are consistent with studies showing deficient amygdala habituation to unpleasant pictures in BPD; and 3) have significant implications for clinical assessment and treatment of BPD, e.g., alternative therapies for BPD such as gradual exposure to unpleasant emotional stimuli or amygdala neurofeedback may aid habituation deficits.

Background: Social cognition, and its relation to social behaviors during pregnancy and postpartum, merits further investigation Additionally, the Covid-19 pandemic has increased the need to administer assessments remotely We aimed to validate remote administration of social cognition tasks (the Movie for the Assessment of Social Cognition (MASC) and the Reading of the Mind in the Eyes (RMET)) in pregnant women Methods: We compared performance of 15 pregnant women (mean age=20 71,SD=6 17) on the MASC administered via zoom and RMET via an online survey platform with 17 non-pregnant women (mean age=38 52,SD=12 46), who completed them in-person prior to the pandemic Participants also completed self-report assessments of social support (Interpersonal Support Evaluation List (ISEL);Social Network Index (SNI)) Results: Since there were significant age differences between groups, age was entered as a covariate MASC scores did not differ between remote (mean=32 07,SD=4 88) and in-person (mean=33 19,SD=7 00) administration, F(1,33)=0 131,p=0 720) RMET accuracy also did not differ between remote (mean=24 53,SD=3 63) and in-person (mean=26 75,SD=7 09) administration, F(1,22)=0 901,p=0 353) RMET and MASC hypomentalizing errors were negatively correlated (r= -0 451, p=0 03) and there was a trend level correlation between the MASC and RMET (r=0 394, p=0 063) MASC accuracy correlated with ISEL total (r=0 415, p=0 05), and RMET with SNI diversity (r=0 547, p=0 02) and number (r=0 521, p=0 03) of people within one’s social network Conclusions: Social cognition tasks correlated with self-reported social support, validating the use of these assessments in pregnant women Results also support the validity of remote administration for social cognition measures, which allows for greater access to vulnerable populations, although pregnancy may have influenced performance Supported By: Icahn School of Medicine at Mount Sinai Keywords: Social Cognition, Remote Assessment, Pregnancy

Background Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the serotonin 2A receptor (5-HT 2A R). We sought to examine the role of the 5-HT 2A R in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT 2A R function in the OFC is a state phenomenon that promotes impulsive aggression. Methods Serotonin 2A receptor availability was measured with positron emission tomography and the selective 5-HT 2A R antagonist radioligand [ 11 C]MDL100907 in two groups of impulsively aggressive personality disordered patients—14 with current physical aggression, and 15 without current physical aggression—and 25 healthy control subjects. Clinical ratings of various symptom dimensions were also obtained. Results Orbitofrontal 5-HT 2A R availability was greater in patients with current physical aggression compared with patients without current physical aggression and healthy control subjects; no differences in OFC 5-HT 2A R availability were observed between patients without current physical aggression and healthy control subjects. No significant differences in 5-HT 2A R availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT 2A R availability was correlated, specifically, with a state measure of impulsive aggression. Conclusions These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT 2A R function in the OFC.

Background Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which poses a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD. Methods We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional brain imaging. Thirty-eight BPD patients with intermittent explosive disorder (BPD-IED) and 36 age-matched healthy control subjects (HCs) received 18fluoro-deoxyglucose positron emission tomography (18FDG-PET) on two occasions with a provocation and nonprovocation version of the PSAP. Mean relative glucose metabolism was measured throughout the cortex, and difference scores (provoked − nonprovoked) were calculated. A whole brain exploratory analysis for the double difference of BPD-IED − HC for provoked − nonprovoked was also conducted. Results BPD-IED patients were significantly more aggressive than HCs on the PSAP. BPD-IED patients also increased relative glucose metabolic rate (rGMR) in OFC and amygdala when provoked, while HCs decreased rGMR in these areas. However, HCs increased rGMR in anterior, medial, and dorsolateral prefrontal regions during provocation more than BPD-IED patients. Conclusions Patients responded aggressively and showed heightened rGMR in emotional brain areas, including amygdala and OFC, in response to provocation but not in more dorsal brain regions associated with cognitive control of aggression. In contrast, HCs increased rGMR in dorsal regions of PFC during aggression provocation, brain regions involved in top-down cognitive control of aggression, and, more broadly, of emotion.

Background Excessive emotional responding is considered to be a hallmark of borderline personality disorder (BPD). The affect-modulated startle response is a reliable indicator of emotional processing of stimuli. The aim of this study was to examine emotional processing in BPD patients (n = 27) and healthy control subjects (n = 21). Methods Participants viewed an intermixed series of unpleasant, borderline-salient (e.g., “hate”), and neutral (e.g., “view”) words and were instructed to think about the meaning of the word for them personally while eyeblink responses were assessed. Results The BPD patients exhibited larger startle eyeblink during unpleasant but not neutral words, indicating exaggerated physiological affect. This finding remained significant when we controlled for comorbid diagnoses, including generalized anxiety disorder and post-traumatic stress disorder. Greater symptom severity was associated with greater affective-startle difference scores (unpleasant-neutral). Conclusions Consistent with the symptom of affective dysregulation, these results suggest an abnormality in the processing of unpleasant emotional stimuli by BPD patients.

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 [χ 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.

Background Borderline personality disorder (BPD) is characterized by an inability to regulate emotional responses. The amygdala is important in learning about the valence (goodness and badness) of stimuli and functions abnormally in BPD. Methods Event-related functional magnetic resonance imaging (MRI) was employed in three groups: unmedicated BPD ( n = 33) and schizotypal personality disorder ( n = 28) participants and healthy control subjects ( n = 32) during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures each presented twice within their respective trial block/run. The amygdala was hand-traced on each participant's structural MRI scan and co-registered to their MRI scan. Amygdala responses were examined with a mixed-model multivariate analysis of variance. Results Compared with both control groups, BPD patients showed greater amygdala activation, particularly to the repeated emotional but not neutral pictures, and a prolonged return to baseline for the overall blood oxygen level-dependent response averaged across all pictures. Despite amygdala overactivation, BPD patients showed blunted self-report ratings of emotional but not neutral pictures. Fewer dissociative symptoms in both patient groups were associated with greater amygdala activation to repeated unpleasant pictures. Conclusions The increased amygdala response to the repeated emotional pictures observed in BPD was not observed in schizotypal patients, suggesting diagnostic specificity. This BPD-related abnormality is consistent with the well-documented clinical feature of high sensitivity to emotional stimuli with unusually strong and long-lasting reactions. The finding of a mismatch between physiological and self-report measures of emotion reactivity in BPD patients suggests they may benefit from treatments targeting emotion recognition.

Background Sexual violence is an important public health problem in the United States, with 13% to 26% of women reporting a history of sexual assault. While unfortunately common, there is substantial individual variability in response to sexual assault. Approximately half of rape victims develop posttraumatic stress disorder (PTSD), while others develop no psychopathology (e.g., trauma-exposed non-PTSD). In this project, we examined the neural mechanisms underlying differences in response to sexual violence, focusing specifically on the deliberate modification of emotional responses to negative stimuli. Methods Using functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) response, we examined the neural circuitry underlying effortful modification of emotional responses to negative pictures in 42 women: 14 with PTSD after sexual trauma, 14 with no psychiatric diagnosis after sexual trauma, and 14 nontraumatized control subjects. Results In response to deliberate attempts to downregulate emotional responses, nontraumatized healthy control subjects were more successful than either trauma-exposed group (PTSD or non-PTSD) in downregulating responses to the negative pictures as measured by subjective rating and BOLD response in regions of prefrontal cortex (PFC). In contrast, after deliberate attempts to upregulate emotional responses, regions of PFC were activated by trauma-exposed non-PTSD subjects more than by healthy control subjects or PTSD subjects. Conclusions Successful downregulation of emotional responses to negative stimuli appears to be impaired by trauma exposure. In contrast, the ability to upregulate emotional responses to negative stimuli may be a protective factor in the face of trauma exposure and associated with resilience.

Background Traumatic experiences may lead to debilitating psychiatric disorders including acute stress disorder and posttraumatic stress disorder. Current treatments for these conditions are largely ineffective, and novel therapies are needed. A cardinal symptom of these pathologies is the reexperiencing of the trauma through intrusive memories and nightmares. Studies in animal models indicate that memories can be weakened by interfering with the postretrieval restabilization process known as memory reconsolidation. We previously reported that, in rats, intraamygdala injection of the glucocorticoid receptor antagonist RU38486 disrupts the reconsolidation of a traumatic memory. Here we tested parameters important for designing novel clinical protocols targeting the reconsolidation of a traumatic memory with RU38486. Methods Using rat inhibitory avoidance, we tested the efficacy of postretrieval systemic administration of RU38486 on subsequent memory retention and evaluated several key preclinical parameters. Results Systemic administration of RU38486 before or after retrieval persistently weakens inhibitory avoidance memory retention in a dose-dependent manner, and memory does not reemerge following a footshock reminder. The efficacy of treatment is a function of the intensity of the initial trauma, and intense traumatic memories can be disrupted by changing the time and number of interventions. Furthermore, one or two treatments are sufficient to disrupt the memory maximally. The treatment selectively targets the reactivated memory without interfering with the retention of another nonreactivated memory. Conclusions RU38486 is a potential novel treatment for psychiatric disorders linked to traumatic memories. Our data provide the parameters for designing promising clinical trials for the treatment of flashback-type symptoms of PTSD.

Through reviewing what is known about the nature, course, and heritability of borderline personality disorder (BPD), we argue for a reconceptualization of this disorder that would lead to its placement on Axis I. Borderline personality disorder is a prevalent and disabling condition, and yet the empirical research into its nature and treatment has not been commensurate with the seriousness of the illness. We not only review empirical evidence about the etiology, phenomenology, and course of the disorder in BPD but we also address fundamental misconceptions about BPD that we believe have contributed to misunderstanding and stigmatization of the disease. Finally, we suggest future directions for research that might permit the identification of core features of this disorder, with a focus on the importance of naturalistic assessments and of assessments through the course of development.

Background Structural abnormalities in prefrontal and cingulate gyrus regions—important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. Methods MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. Results Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. Conclusions The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.

Background Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). Methods We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color–Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV–R), and the Wechsler Adult Intelligence Scale vocabulary and block design. Results Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV–R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV–R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score ( r = −.32, p Conclusions Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV–R immediate and delayed recall (a learning–recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Dysregulation of the central serotonergic (5-HT) system has been associated with personality disorders and with suicidality, impulsive aggression, and irritability utilizing CSF 5-HIM and fenfluramine challenge test, which is not selective for any serotonin receptor subtype as a serotonergic measure. A dose response study of ipsapirone (1PS), a 5-HT-1A agonist, has shown that it is a useful probe of 5-HT1A function in normal subjects when temperature and cortisol are used as response variables. To preliminarily investigate the potential usefulness of IPS as a possible 5-HT-subtype specific probe in personality disorder patients, we did a pilot study evaluating the response to IPS in patients and normal controls (NC). Twenty mg of IPS was administered orally in a placebo-controlled double-blind design to l0 NC and 9 patients with DSM-III-R personality disorder. Temperature, CORT, and prolactin (PRL) levels were measured prior to IPS/placebo administration and at half-hour intervals over the next 3 hours. IPS significantly reduced temperature in all subjects (F[ 1,21 ] ~ 13.3, p < 0.01 ) and increased CORT levels (F[ 1,22] 9.27, p < 0.01). There was no diagnosis by drug interaction in either of the two measures. The temperature response to IPS correlated inversely with PRL response to fenfluramine (r 0.82, p < 0.01 ) and positively with the Barratt Impulsiveness Scale (Risk Taking subscale; r 0.86, p < 0.01). Although this sample size was too small to draw any definitive conclusions, temperature and possibly CORT response to IPS and their clinical correlates may be useful measures in future studies of impulsivity in personality disordered patients.

Background:Decreased serum cholesterolhas beerr associated with impulsive and aggressive behaviors. Abnormal central serotonergic activity,as reflectedby decreasedprolactirrresponsesto fenfluramine, has been correlatedto impulsivityand aggressionin personalitydisordered patients. This study was designedto explore the relationship betweenserumcholesterollevels,serotonergicindicesand measuresof impulsivityand aggressionin personalitydisorderedpatienta.Method: Forty-twopersonalitydisorderedpatients(DSMIHR-20femalesand 22 males,age 37.1+ 8.5),including14patientswithBPD(age:34.2t 6.6; 10female,4 male),and28patientswithotherpersonalitydisorders(age: 38.5t9.l; 10female,18male)wereexaminedforevidenceof irritability and aggressionby self reportas measuredby the Buss-DurkeeHostility Inventory(BDHI),and for evidenceof impulsivityby self report as measuredby the BarratI ImpulsivityScale (BIS).Centralaerotonergic activitywas measuredby the prolactinresponseto fenfluratninechallenge.Fastingserumcholesterolwas measuredby standardenzymatic assay as part of the initial medicalscreening.All patients’thyroidand liverfunctiontests werealso measuredduringinitialmedicrdsermting, and were determinedto be withinnormallimits.Results:An ANOVA wasperformedwithfactorsof genderartddiagnosis,lookingat twoway interactionsbetweenthe factors and serum cholesterol.A significant relationshipwas foundbetweenborderlinediagnosisandreducedsemm cholesterol,(BPDchol=166.8t32.2, non-BPD=192.6*33.6,F= 1.09, p