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Long-standing theories of borderline personality disorder (BPD) suggest that symptoms develop at least in part from childhood adversity. Emotion dysregulation may meaningfully mediate these effects. The current study examined three factors related to emotion dysregulation—alexithymia, affective lability, and impulsivity—as potential mediators of the relation between childhood adversity and BPD diagnosis in 101 individuals with BPD and 95 healthy controls. Path analysis compared three distinct models informed by the literature. Results supported a complex mediation model wherein (a) alexithymia partially mediated the relation of childhood adversity to affective lability and impulsivity; (b) affective lability mediated the relation of childhood adversity to BPD diagnosis; and (c) affective lability and impulsivity mediated the relation of alexithymia to BPD diagnosis. Findings suggest that affective lability and alexithymia are key to understanding the relationship between childhood adversity and BPD. Interventions specifically targeting affective lability, impulsivity, and alexithymia may be particularly useful for this population.

This article reviews the most salient neurobiological information available about borderline personality disorder (BPD) and presents a theoretic model for what lies at the heart of BPD that is grounded in those findings. It reviews the heritability, genetics, and the biological models of BPD, including the neurobiology of affective instability, impaired interoception, oxytocin and opiate models of poor attachment or interpersonal dysfunction, and structural brain imaging over the course of development in BPD; and posits that the core characteristic of BPD may be an impairment in emotional interoception or alexithymia.

A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype.

Despite considerable phenomentological differences between borderline personality disorder (BPD) and schizotypal personality disorder (SPD), research increasingly provides evidence that some BPD symptoms overlap with SPD symptoms (e.g., disturbed cognitions). We examined the cingulate, a brain region implicated in the pathophysiology of both disorders, to determine similarities/differences between the groups, and similarities/differences from healthy controls (HC's). 3T structural and diffusion tensor magnetic resonance imaging scans were acquired in BPD (n = 27), SPD (n = 32), HC's (n = 34). Results revealed that BPD patients exhibited significantly lower FA in posterior cingulate white matter compared to HC's (p = 0.04), but SPD patients did not.

BACKGROUND: Cognitive impairment is a prominent feature that is closely linked to functional outcome in schizophrenia-spectrum patients, such as those with schizotypal personality disorder (SPD). Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate these cognitive deficits, although there have been few controlled experiments of this mechanism. METHODS: Twenty-seven medication-free patients with SPD who demonstrated cognitive impairment (i.e., scoring more than 1 SD below healthy control means of measures of cognition) were enrolled in a randomized, double-blind, placebo-controlled trial of the full D1 receptor agonist, dihydrexidine (DAR-0100A; 15 mg/150 ml of normal saline administered intravenously over 30 min). We administered the MATRICS Clinical Consensus Battery (MCCB) during drug/placebo infusion. Using a crossover design, study procedures occurred over four consecutive days, with MCCB testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2–4; administration of drug/placebo order was randomly assigned, with 14 participants receiving DAR-0100A first. RESULTS: Compared with cognitive performance during placebo, administration of DAR-0100A was associated with significantly better verbal learning (HVLT score, F(1, 24)=5.1,p=.03). DAR-0100A was adequately tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, e.g., co-administered normal saline. DISCUSSION: These findings lend further clinical support to the potential D1 receptor agonists to treat cognitive impairments in schizophrenia-spectrum disorders. Future research, including in schizophrenia samples, is warranted.

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

Patients with borderline personality disorder (BPD) are at high risk for suicidal behavior. However, many BPD patients do not engage in suicidal behavior. In this study, we compared clinical features of BPD patients with or without a history of suicide attempts and healthy volunteers. Compared with healthy volunteers, both BPD groups had higher Affective Lability Scale (ALS), ALS – Depression-Anxiety Subscale, Barratt Impulsivity Scale (BIS), and Lifetime History of Aggression (LHA) scores and were more likely to have a history of temper tantrums. BPD suicide attempters had higher ALS, ALS – Depression-Anxiety Subscale and LHA scores and were more likely to have a history of non-suicidal self-injury or temper tantrums compared to BPD non-attempters. Also, BPD suicide attempters were more likely to have a history of comorbid major depressive disorder and less likely to have comorbid narcissistic personality disorder (NPD) in comparison to BPD non-attempters. About 50% of study participants in each BPD group had a history of comorbid substance use disorder (SUD). Our study indicates that BPD patients with a history of suicide attempt are more aggressive, affectively dysregulated and less narcissistic than BPD suicide non-attempters.

Objective Despite advances in suicide prevention implemented throughout the US Department of Veterans Affairs (VA) including the hiring of Suicide Prevention Coordinators (SPCs) at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services, suicide by veterans remains a critical problem affecting 20 veterans daily. Few empirically based treatment strategies for suicide prevention for postdeployment military personnel exist. This study aimed to test whether dialectical behavior therapy (DBT), one of the few psychosocial treatments with proven efficacy in diminishing suicidal behavior in individuals with personality disorder, can be applied to veterans irrespective of personality diagnosis. Methods From January 2010 to December 2014, 91 nonpsychotic veterans at high risk for suicide (61 men, 30 women) were randomly assigned to a 6-month treatment trial at a veterans' medical center comparing standard DBT to treatment as usual (TAU) and followed for 6 months after trial completion. Primary outcome was suicide attempts, measured with the Columbia-Suicide Severity Rating Scale, and secondary outcomes were suicide ideation, depression, hopelessness, and anxiety. There were no exclusions pertaining to substance abuse, homelessness, or medical comorbidity. Results Both DBT and TAU resulted in improvements in suicidal ideation, depression, and anxiety during the course of the 6-month treatment trial that did not differ between treatment arms. Survival analyses for suicide attempts and hospitalizations did not differ between treatment arms. However, DBT subjects utilized significantly more individual mental health services than TAU subjects (28.5 ± 19.6 vs 14.7 ± 10.9, F₁,₇₇ = 11.60, P = .001). Conclusions This study is the first to examine 6-month DBT in a mostly male, veteran population. Increased mental health treatment service delivery, which included enhanced monitoring, outreach, and availability of a designated SPC, did not yield statistically significant differences in outcome for veterans at risk for suicide in TAU as compared to the DBT treatment arm. However, both treatments had difficulty with initial engagement post-hospitalization. Future studies examining possible sex differences and strategies to boost retention in difficult-to-engage, homeless, and substance-abusing populations are indicated. Trial registration ClinicalTrials.gov identifier: NCT02462694.

Recent studies demonstrate that veterans exhibit higher suicide risk compared with the general U.S. population. A prior suicide attempt is a well-documented predictor of suicide death. Despite increased attention to clinical risk factors of suicide and efforts to develop psychosocial interventions to reduce suicide risk, the underlying biological factors that confer this risk are not well understood. This study examined affect-modulated startle (AMS) during a series of intermixed unpleasant, neutral, and pleasant pictures in a sample of 108 demographically-matched veterans at low (passive ideators: n = 26) and high risk (active ideators: n = 29; single attempters: n = 28; and multiple attempters: n = 25) for suicide based on the Columbia Suicide Severity Rating Scale. An exploratory aim involved a longitudinal component in a subset of the high-risk sample that went on to participate in a randomized 6-month clinical trial. We investigated whether baseline AMS predicts a subsequent suicide attempt at 12-month follow-up. Compared with the other three groups, multiple attempters showed greater startle potentiation during unpleasant pictures and deficient overall startle habituation from early to later trials. The groups did not differ in startle during neutral or pleasant pictures, or self-reported picture valence. Greater startle during unpleasant pictures was associated with greater emotion dysregulation as measured by the Difficulties in Emotion Regulation Scale and a future suicide attempt assessed prospectively at 12-month follow-up. These findings suggest that startle potentiation during unpleasant pictures in multiple-suicide attempters is a promising psychophysiological biomarker of suicide risk and underscore the clinical importance of targeting emotion dysregulation in the treatment of patients at-risk for suicide.

Impaired cognition is a hallmark of schizophrenia spectrum disorders, including schizotypal personality disorder, and it is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition, augmenting other rehabilitation efforts in schizophrenia, and effecting gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted, but the effects of augmentation on combined therapies, such as cognitive remediation and social skills training, have not been studied.Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation and social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the University of California San Diego Performance-Based Skills Assessment (UPSA).A statistically significant pre- versus posttreatment effect was observed for MCCB speed of processing, verbal learning, and visual learning and UPSA total score. A significant time-by-medication (guanfacine, placebo) interaction was observed for MCCB reasoning and problem solving and UPSA total score; the time-by-treatment interaction approached significance for MASC hypomentalizing errors.Both guanfacine and cognitive remediation plus social skills training were well tolerated, with no side effects or dropouts. Participants treated with cognitive remediation, social skills training, and guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared with those treated with cognitive remediation, social skills training, and placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder, and guanfacine appears to be a promising pharmaceutical augmentation to this psychosocial intervention.

Given the common use of self-report questionnaires to assess schizotypy in personality pathology and schizophrenia research, it is important to determine the concordance between self-report and clinician ratings. 250 individuals with schizotypal personality disorder (SPD) and 116 community controls (CTR) were assessed on schizotypal traits using a clinical interview, the Structured Interview for DSM-IV Personality disorders (SIDP), and a self-report questionnaire, the Schizotypal Personality Questionnaire (SPQ). Ordinal logistic regressions examined concordance between self-reported and clinician-rated scores in CTR and SPD separately. Analyses of variance examined how the SPQ performed on differentiating between CTR with low schizotypy, CTR with high schizotypy, and SPD. For both CTR and SPD, higher SPQ subscale scores were significantly associated with higher clinician ratings on the respective SIDP items for the Ideas of Reference, Magical Thinking, Unusual Perceptual Experience, Suspiciousness, and Social Anxiety items, but not the Odd Speech or Limited Affect items. Higher SPQ subscale scores for Odd Behavior and Lack of Close Friends were significantly associated with the clinician-rated SIDP item scores in CTR but not SPD. CTR with low schizotypy scored lower on all SPQ subscales than CTR with high schizotypy, who did not differ from SPD. Self-report ratings are concordant with clinician ratings for positive schizotypal traits, whereas certain disorganization and interpersonal traits are not, particularly for individuals with SPD. The SPQ can differentiate between high and low schizotypy controls, but not between high schizotypy controls and individuals with SPD. Assessment of schizotypal traits should include both self-report questionnaires and clinician ratings.

Research suggests many shared clinical features across individuals with Schizotypal Personality Disorder (SPD) and Borderline Personality Disorder (BPD), including problems with attention/ executive functioning and mood. Therefore, aspects of these areas of functioning were compared in SPD and BPD to better characterize their respective difficulties. BPD, SPD, and healthy control (HC) participants were administered measures of cognitive and mood functioning. Compared with healthy controls, SPD patients performed significantly worse on aspects of the Delayed-Matching- to-Sample task, a measure of short-term visual memory abilities; however, the individuals with BPD did not differ from healthy controls. Neither of the patient groups differed from HC’s on measures of processing speed or planning. With regard to mood functioning, the BPD group exhibited significantly higher levels of affective disturbance (e.g., sadness, fear, anger) compared with the SPD patients and HCs. Overall, findings suggest different patterns of fronto-subcortical weakness in each patient group. While SPD patients exhibited relative weakness with short-term memory, BPD patient performance on such measures did not reveal relative weakness compared with HCs but did implicate problems with mood.

Background: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplored question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli. Methods: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, selfreported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task. Results: Avoidant patients showed greater state and trait-related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyperreactivity during reappraisal anticipation, and this hyper-reactivity effect was positively associated with increasing self-reported anxiety levels. Limitations: Our finding of exaggerated amygdala activity during reappraisal anticipation could reflect anxiety about the impending need to reappraise, anxiety about the certainty of an upcoming negative image, or anxiety relating to anticipated scrutiny of task responses by the experimenters. While we believe that all of these possibilities are consistent with the phenomenology of avoidant personality disorder, future research may clarify this ambiguity. Conclusions: These results suggest that amygdala reactivity in anticipation of receiving negative social information may represent a key component of the neural mechanisms underlying the heightened anxiety present in avoidant patients. Published by Elsevier B.V.

Impaired interpersonal functioning is a core feature of borderline, schizotypal, and avoidant personality disorders characterized by abnormal social information processing; however, pharmacologic treatments targeting social cognition are currently lacking. Oxytocin is a novel treatment for social cognitive abnormalities that has yielded promising preliminary results in the autism spectrum, social anxiety disorders, and schizophrenia. Here, we describe the main components of social cognition and review the biology of the oxytocinergic system and the hypothesized models and mechanisms through which exogenous oxytocin modulates social cognition. We then review the studies on the effect of oxytocin administration on social cognition and their application to the treatment of personality disorders. We also review the preliminary evidence supporting the use of oxytocin as an adjunct to non-pharmacologic interventions. Finally, we describe the main challenges that need to be addressed to be able to use oxytocin effectively in clinical populations.

Neuroimaging may predict response to cognitive remediation therapy and social skills training (CRT + SST) in schizophrenia. Identifying biological predictors of response is crucial for treatment decision making given not all patients respond to such interventions. Nineteen veterans with schizophrenia enrolled in an 8-week trial of CRT + SST. Ten participants completed diffusion tensor imaging (DTI) at baseline. Baseline fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and overall average FA predicted improvements in visual-spatial working memory, and social cognition, respectively. Neuroimaging may be useful in identifying therapeutic targets in schizophrenia.

Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging. We were particularly interested in investigating patterns of activity in insula, given its significant role in affective integration, and in amygdala, given its association with appraisal of aversive stimuli and its frequent coactivation with insula. We found significant habituation behaviorally along with decreases in amygdala, occipital cortex and ventral prefrontal cortex (PFC) activity with repeated presentation, whereas bilateral posterior insula, dorsolateral PFC and precuneus showed increased activation. Posterior insula activation during image presentation was correlated with greater negative affect ratings for novel presentations of negative images. Further, repeated negative image presentation was associated with increased functional connectivity between left posterior insula and amygdala, and increasing insula–amygdala functional connectivity was correlated with increasing behavioral habituation. These results suggest that habituation is subserved in part by insula–amygdala connectivity and involves a change in the activity of bottom-up affective networks.

BackgroundBorderline personality disorder (BPD) often presents during adolescence. Early detection and intervention decreases its subsequent severity. However, little is known about early predictors and biological underpinnings of BPD. The observed abnormal functional connectivity among brain regions in BPD led to studies of white matter, as the neural substrate of connectivity. However, diffusion tensor imaging (DTI) studies in adult BPD have been inconclusive, and, as yet, there are no published DTI studies in borderline adolescents.MethodsWe conducted DTI tractography in 38 BPD patients (14-adolescents, 24-adults) and 32 healthy controls (13-adolescents, 19-adults).ResultsWe found bilateral tract-specific decreased fractional anisotropy (FA) in inferior longitudinal fasciculus (ILF) in BPD adolescents compared to adolescent controls. ILF FA was significantly higher in adolescent controls compared to BPD adolescents, BPD adults and adult controls (Wilks F(3,57) = 3.55, p

Neurobiological studies have focused primarily on DSM-IV axis I disorders, as they display extensive, and often severe and episodic symptomatology. However, there is an emerging focus on the neurobiology of personality disorders, consisting largely of maladaptive traits that impair functioning and adaptation to the environment. These clusters of maladapative traits are partially heritable, associated with specific candidate genes that are beginning to be identified by preliminary genetic studies, and are grounded in specific neurocircuitry changes; borderline personality disorder (BPD), antisocial personality disorder (ASPD), and schizotypal personality disorder (STPD) have been the most studied and have the largest empirical evidence. Greater understanding of the neurobiological grounding of these disorders will in part inform the conceptualization of personality disorders in the new nonaxial diagnostic system in DSM−5.

The authors aimed to understand the role of alexithymia in borderline personality disorder (BPD). A total of 79 BPD patients, 76 healthy controls, and 39 patients with avoidant personality disorder (AVPD) were included. Alexithymia and its influence on interpersonal functioning were assessed. The authors explored group differences in empathy in relation to interpersonal function, and they measured responses to emotional pictures with a computer task in which subjects focused either on the experience of the individual in the picture or the subject's own imagined experience. Patients with BPD and AVPD had higher alexithymia than those in the control group. Patients with BPD had more difficulty identifying their own emotions than patients with AVPD. Patients with BPD reported poorer ability to take the perspective of others, but higher distress; they showed intact "empathic concern." Differences in computer task performance were clearest during self-relevant responses to negatively valenced pictures. BPD patients are highly responsive to the feelings of others, but they are impaired in identifying/describing feelings and in taking the perspective of others.

Consistent with the clinical picture of milder symptomatology in schizotypal personality disorder (SPD) than schizophrenia, morphological studies indicate SPD abnormalities in temporal lobe regions but to a much lesser extent in prefrontal regions implicated in schizophrenia. Lower fractional anisotropy (FA), a measure of white-matter integrity within prefrontal, temporal, and cingulate regions has been reported in schizophrenia but has been little studied in SPD.The study aim was to examine temporal and prefrontal white matter FA in 30 neuroleptic-naïve SPD patients and 35 matched healthy controls (HCs). We hypothesized that compared with HCs, SPD patients would exhibit lower FA in temporal lobe and anterior cingulum regions but relative sparing in prefrontal regions.We acquired diffusion tensor imaging (DTI) in all participants and examined FA in the white matter underlying Brodmann areas (BAs) in dorsolateral prefrontal (BAs 44, 45, and 46), temporal lobe (BAs 22, 21, and 20), and cingulum (BAs 25, 24, 31, 23, and 29) regions with a series of analyses using multivariate analysis of variance.Compared with HCs, the SPD group had significantly lower FA in the left temporal lobe but not prefrontal regions. In the cingulum, FA was lower in the SPD group in the posterior regions (BAs 31 and 23), higher in the anterior (BA 25) regions and lower overall in the right but not the left cingulum. Among the SPD group, lower FA in the cingulum was associated with more severe negative symptoms (e.g., odd speech).Similar to schizophrenia, our results indicate cingulum-temporal lobe FA abnormalities in SPD and suggest that cingulum abnormalities are associated with negative symptoms.

To identify aspects of parental burden associated with borderline personality disorder (BPD), an anonymous internet survey linked to BPD support websites was developed for parents to complete on their BPD offspring and unaffected siblings. The questions cover aspects of the child's life from pregnancy through young adulthood, and query about the impact of the child's BPD on six domains of the parent's life, including physical and emotional health, marriage, job, standard of living, social life, and career trajectory. Additionally, financial burden was assessed with questions pertaining to insurance and out-of pocket costs associated with the BPD disorder. BPD offspring were identified by meeting diagnostic criteria embedded within the survey and having been given a diagnosis of BPD by a professional at some point in their life. We report on 233 female offspring meeting strict criteria for BPD. Parents of daughters with BPD endorsed varying levels of impact on the six domains comprising burden with the largest impact on emotional health which was impacted in over 88% of the respondents. Over 50% of parents endorsed four or greater of the six burden items. Particular aspects of the offspring's BPD symptom profile correlated with intensity of parental burden included including problems in adolescence with acting out behavior (p < .000), property destruction (.003), delusional symptoms (.007), and hallucinatory symptoms (.008). A subgroup of respondents provided data on specific financial expenses. The average and median out-of-pocket expense was $60,087, and $10,000. Insurance costs totaled an average of $108,251 with a mean of $20,000. The average cost per year after diagnosis was $14,606 out-of-pocket and $45,573 billed to insurance. The median cost per year after diagnosis was $3,667 out-of-pocket, and $12,500 billed to insurance. After adjusting for household income, a female proband who had been raped incurred roughly $40,000 more in BPD-related costs, while a diagnosis of conduct disorder led to about $50,000 in additional costs. Parents of female offspring with BPD experience burden in multiple domains of their life and many have incurred substantial financial expense. Increasing awareness of co-morbid conditions in the BPD proband that significantly increase parental burden may be indicators for the provision of increased family support.

Background There is a decreased serotonergic function in impulsive aggression and borderline personality disorder (BPD), and genetic association studies suggest a role of serotonergic genes in impulsive aggression and BPD. Only one study has analyzed the association between the tryptophan-hydroxylase 2 (TPH2) gene and BPD. A TPH2 “risk” haplotype has been described that is associated with anxiety, depression and suicidal behavior. Methods We assessed the relationship between the previously identified “risk” haplotype at the TPH2 locus and BPD diagnosis, impulsive aggression, affective lability, and suicidal/parasuicidal behaviors, in a well-characterized clinical sample of 103 healthy controls (HCs) and 251 patients with personality disorders (109 with BPD). A logistic regression including measures of depression, affective lability and aggression scores in predicting “risk” haplotype was conducted. Results The prevalence of the “risk” haplotype was significantly higher in patients with BPD compared to HCs. Those with the “risk” haplotype have higher aggression and affect lability scores and more suicidal/parasuicidal behaviors than those without it. In the logistic regression model, affect lability was the only significant predictor and it correctly classified 83.1% of the subjects as “risk” or “non-risk” haplotype carriers. Conclusions We found an association between the previously described TPH2 “risk” haplotype and BPD diagnosis, affective lability, suicidal/parasuicidal behavior, and aggression scores.

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.

Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one's self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation.

Background Abnormalities in cognition and social cognition represent a core feature of the schizophrenia spectrum disorders. Schizotypal personality disorder (SPD) is a milder disorder within the schizophrenia spectrum, characterized by attenuated, schizophrenia-like traits without overt psychosis. Study 1: Working memory impairments are a core cognitive deficit in schizophrenia and SPD. The dopamine D1 receptor is a promising target to enhance working memory. We aimed to test the effect of the D1 agonist dihydrexidine (DAR-0100A) to enhance working memory in patients with SPD. Study 2: Oxytocin modulates social cognition. However, oxytocin’s effect on social cognitive errors in the schizophrenia spectrum remains unexplored. We aimed to: 1) characterize social cognitive (mentalizing) errors in SPD patients and test their relationship with positive and negative symptoms of psychosis; 2) test the effect of intranasal oxytocin on mentalizing errors. Methods Study 1: We performed a randomized, double blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline i.v. over 30 min) in medication-free SPD patients (n=16). Study 2: Subjects: 15 SPD patients, 15 healthy controls [HC], and 15 psychiatric controls (PC). Intervention: intranasal oxytocin 24/40IU/placebo. Measures: Movie for the Assessment of Social Cognition (MASC), a naturalistic video task measuring mentalizing accuracy, “no mentalizing” errors, “hypomentalizing” errors and “hypermentalizing” errors. The “hyper-hypomentalizing ratio” can be computed to capture the predominant mentalizing tendency; PANSS; Schizotypal Personality Questionnaire, SPQ. Mentalizing measures were compared across groups (SPD, HC, PC), and treatments (oxytocin 24IU/40IU vs placebo) using ANOVA. Pearson correlations assessed the relationship between social cognition and symptoms. Results Study 1: Treatment with dihydrexidine (DAR-0100A) was associated with significantly improved working memory performance relative to placebo, with a very large effect size (Cohen’s d=1.14). Study 2: SPD patients had lower mentalizing accuracy (F=10.11;df=1;p=0.003), made more “No mentalizing” or “hypomentalizing” errors (F=12.92;df=1;p=0.001), and had lower hyper-hypomentalizing ratios than HCs (F=2.84; df=1;p=0.099,trend level). In a subset of patients –including 8 SPD-, a single dose of intranasal oxytocin significantly increased the hyper-hypomentalizing ratio (F=6.84, df=1,p=0.019) and increased visual attention to social cues. “No mentalizing” and “hypomentalizing” errors were significantly correlated with negative symptoms. “Hypermentalizing” errors were significantly correlated with positive symptoms and the “ideas of reference” and “suspiciousness” SPQ subscales. Discussion Study 1: These preliminary findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. Study 2: As hypothesized, SPD patients had impaired, less accurate social cognition, and made more “no mentalizing” and “hypomentalizing” errors, correlated with negative symptoms. Conversely, “hypermentalizing errors” were correlated with positive symptoms. Oxytocin increased the tendency to hypermentalize. This effect may normalize the abnormalities found at baseline in SPD patients. These results support the role of social cognitive impairments as an underlying factor of positive and negative symptoms of psychosis, with specific associations with paranoid and delusional traits. Our results also suggest that intranasal oxytocin modulates social cognitive errors in the psychosis spectrum.

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.

Borderline personality disorder (BPD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder's eti- ology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of tar- geted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Over- all, the results provide partial support for the use of behavioral measures of aggression and motor impul- sivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples.

This study examined the influence of various forms of childhood abuse on basal cortisol levels in a sample of adults with Axis II personality disorders. Participants included 63 adults (n = 19 women) who provided basal plasma cortisol samples and completed the Childhood Trauma Questionnaire. Linear regression analyses that included all 5 subscales (ie, sexual abuse, physical abuse, emotional abuse, physical neglect and emotional neglect) demonstrated that physical abuse was related to lower cortisol levels (beta = -.43, P = .007), consistent with prior literature. In contrast, physical neglect was associated with higher cortisol (beta = .36, P = .02), after controlling for other forms of abuse. Results are consistent with the view that childhood trauma has long-lasting neurobiological effects and suggest that different forms of trauma may have distinct biological effects.

While it is premature to provide a simple model for the vulnerability to the development of either borderline (BPD) or schizotypal (SPD) personality disorder, it is clear that these heritable disorders lend themselves to fruitful neurobiological exploration. The most promising findings in BPD suggest that a diminished top-down control of affective responses, which is likely to relate to deceased responsiveness of specific midline regions of prefrontal cortex, may underlie the affective hyperresponsiveness in this disorder. In addition, genetic and neuroendocrine and molecular neuroimaging findings point to a role for serotonin in this affective disinhibition. Clearly SPD falls within the schizophrenia spectrum, but precisely the nature of what predicts full-blown schizophrenia as opposed to the milder symptoms of SPD is not yet clear.

Frontolimbic dysfunction is observed in borderline personality disorder (BPD), with responses to emotional stimuli that are exaggerated in the amygdala and impaired in the anterior cingulate cortex (ACC). This pattern of altered function is consistent with animal models of stress responses and depression, where hypertrophic changes in the amygdala and atrophic changes in the ACC are observed. We tested the hypothesis that BPD patients exhibit gross structural changes that parallel the respective increases in amygdala activation and impairment of rostral/subgenual ACC activation.Twelve unmedicated outpatients with BPD by DSM-IV and 12 normal control (NC) subjects underwent a high-resolution T1-weighted structural MRI scan. Relative gray matter concentration (GMC) in spatially-normalized images was evaluated by standard voxel-based morphometry, with voxel-wise subject group comparisons by t test constrained to amygdala and rostral/subgenual ACC.The BPD group was significantly higher than NC in GMC in the amygdala. In contrast, the BPD group showed significantly lower GMC than the NC group in left rostral/subgenual ACC.This sample of BPD patients exhibits gross structural changes in gray matter in cortical and subcortical limbic regions that parallel the regional distribution of altered functional activation to emotional stimuli among these same subjects. While the histological basis for GMC changes in adult clinical populations is poorly-known at present, the observed pattern is consistent with the direction of change, in animal models of anxiety and depression, of neuronal number and/or morphological complexity in both the amygdala (where it is increased) and ACC (where it is decreased).

Magnetic resonance imaging (MRI) studies have revealed fronto-temporal cortical gray matter volume reductions in schizophrenia. However, to date studies have not examined whether age- and sex-matched unmedicated schizotypal personality disorder (SPD) patients share some or all of the structural brain-imaging characteristics of schizophrenia patients. We examined cortical gray/white matter volumes in a large sample of unmedicated schizophrenia-spectrum patients (n = 79 SPD, n = 57 schizophrenia) and 148 healthy controls. MRI images were reoriented to standard position parallel to the anterior–posterior commissure line, segmented into gray and white matter tissue types, and assigned to Brodmann areas (BAs) using a postmortem-histological atlas. Group differences in regional volume of gray and white matter in the BAs were examined with MANOVA. Schizophrenia patients had significantly reduced gray matter volume widely across the cortex but more marked in frontal and temporal lobes. SPD patients had reductions in the same regions but only about half that observed in schizophrenia and sparing in key regions including BA10. In schizophrenia, greater fronto-temporal volume loss was associated with greater negative symptom severity and in SPD, greater interpersonal and cognitive impairment. Overall, our findings suggest that increased prefrontal volume in BA10 and sparing of volume loss in temporal cortex (BAs 22 and 20) may be a protective factor in SPD which reduces vulnerability to psychosis.

SUMMARY Biological understanding of a personality disorder is best achieved by examining the disorder's component dimensions, which for borderline personality disorder include impulsive aggression and affective instability. Current biological research into BPD aims to identify the neurotransmitters and brain regions implicated in each of these key domains. Because of advancing technologies and analytic strategies, structural and functional neuroimaging are at the forefront of such efforts. Structural neuroimaging, primarily in the form of magnetic resonance imaging (MRI) scans, gives information about the anatomy of the brain, while functional neuroimaging, primarily functional MRI (fMRI) and positron emission tomography (PET) scans, gives information about brain activity and neurotransmitter systems at the molecular level. BPD neuroimaging studies to date have implied the involvement of several neurotransmitter systems, principally serotonin, along with dysfunction of select brain regions, including the ...

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.

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

A dimensional approach to die study of personality disorders proposes that abnormalities in cognitive control, affective instability, impulsivity/aggression and anxiety, are biologically mediated and range from Axis I disorders to more chronic, milder disturbances of personality. This approach provides a framework for investigating the neurobiological underpinnings of personality disorders and possible therapeutic interventions. The interplay between biological temperament and environmental adversity contribute to personality dysfunction and this idea is reflected in treatment approaches such as dialectical behavioral therapy. The current neurobiology and specific treatments, both pharmacological and psychosocial, are reviewed. Connections between the biological underpinnings and treatment strategies are presented. Despite the numerous limitations in the treatment literature, therapeutic improvement is possible for individuals with personality disorders.

Borderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature.In the present study we investigated group differences among 29 BPD patients, 27 AvPD patients, and 29 healthy controls (HC) in structural brain volumes using voxel-based morphometry (VBM) in five anatomically-defined regions of interest: amygdala, hippocampus, medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). We also examined the relationship between individual differences in brain structure and self-reported anxiety and affective instability in each group.We observed reductions in MPFC and ACC volume in BPD relative to HC, with no significant difference among patient groups. No group differences in amygdala volume were found. However, BPD and AvPD patients each showed a positive relationship between right amygdala volume and state-related anxiety. By contrast, in HC there was an inverse relationship between MPFC volume and state and trait-related anxiety as well as between bilateral DLPFC volume and affective instability.Current sample sizes did not permit examination of gender effects upon structure-symptom correlations.These results shed light on potentially protective, or compensatory, aspects of brain structure in these populations-namely, relatively reduced amygdala volume or relatively enhanced MPFC and DLPFC volume.

Research evaluating mental state identification in individuals with borderline pathology has yielded inconsistent results; contradictory findings were hypothesized to be driven by moderating effects of childhood trauma. Participants were 105 ethnically diverse men and women who exhibited a range of borderline pathology measured by Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for borderline personality disorder. Mental state identification accuracy was measured using the Reading the Mind in the Eyes Test (RMET). Greater childhood abuse, but not childhood neglect, was associated with enhanced mental state identification accuracy on negative stimuli, when controlling for dissociation (ps < .05); these findings could not be explained by reaction time (RT) or response bias. Childhood abuse and childhood neglect were not related to mental state identification accuracy on neutral or positive stimuli, and they did not moderate the relationship between borderline pathology and mental state identification accuracy on negative, neutral, or positive stimuli. Borderline pathology was not independently related to mental state identification accuracy on negative, neutral, or positive stimuli. Greater childhood neglect, but not childhood abuse, was related to slower RTs on negative, neutral, and positive stimuli (ps < .05). Results underline the importance of separately assessing childhood abuse and childhood neglect and of controlling for dissociation, and they suggest borderline pathology may not universally hinder complex mental state identification.

The articles assembled in this special issue demonstrate the broadening acceptance that a failure of "mentalization" is central in borderline personality disorder (BPD). This idea has emerged from a number of places, from astute clinicians who recognized that individuals with BPD were often limited in their ability to recognize and describe their own emotions to empirical work on emotion recognition in BPD. These articles provide a compelling argument that mentalization, with its relatively distinct and testable cognitive components, is a fertile ground for translational research. They also suggest a pathway by which empirical studies can illuminate clinical understanding. To highlight this point, it is now the routine to explain the laboratory evidence for deficits in emotional interoception to patients with BPD. This has been useful in helping to explain the internal and nuanced nature of patients' difficulties (apparent in laboratory testing but not obvious in casual encounters. This translational discussion with patients maps very closely onto an approach the editors argue for in this special issue.

Gender is an important variable in the study of mental health because of the actual and perceived differences between men and women. Relatively little is known how males and females differ in their manifestations of antisocial personality disorder (ASPD). Demographic and clinical features of 323 participants with ASPD were assessed and recorded. Women had fewer episodes of antisocial behavior involving or not involving police, higher scores on the Childhood Trauma Questionnaire (CTQ) and on Emotional Abuse and Sexual Abuse subscales of the CTQ compared to men. CTQ scores positively correlated with the number of episodes of antisocial behavior involving police in men but not in women. The percentage of patients with comorbid borderline and histrionic personality disorders was higher and the percentage of participants with cocaine use disorder was lower among women compared to men. Comorbid alcohol use disorder was frequent in both groups, while a higher percentage of women had comorbid mood disorders compared to men. Logistic regression analysis demonstrates that CTQ scores, histrionic personality disorder, and antisocial behavior involving the police drive the difference between the groups. Our findings indicate that treatment of individuals with ASPD should focus on the management of comorbid psychiatric disorders.

We previously reported that subjects with a schizophrenia spectrum personality disorder (ie, an odd cluster personality disorder), of which the prototype is schizotypal personality disorder, show cognitive impairment in circumscribed areas (working memory) compared with healthy control subjects, and that amphetamine administration improves working memory in subjects with schizotypal personality disorder. In this larger series, we wanted to determine whether amphetamine treatment ameliorates working memory impairment using three groups: subjects with a schizophrenia spectrum personality disorder (ie, schizotypal, paranoid, or schizoid personality disorder), other (subjects with nonschizophrenia spectrum) personality disorder, and healthy volunteers. We hypothesized that amphetamine treatment would improve cognitive function in domains in which subjects with schizophrenia spectrum personality disorder show impairment compared with healthy volunteers and the other personality disorder group. Overall, amphetamine treatment did not improve performance in any task compared with placebo, and there was no group by drug interaction in the total sample. However, when the sample was restricted to the subjects who showed impairment at baseline, amphetamine treatment improved visuospatial working memory. In the total patient sample, amphetamine treatment reduced negative symptoms, whereas positive symptoms remained unchanged. Amphetamine treatment improves working memory in those subjects with cognitive impairment at baseline, most of whom meet criteria for a schizophrenia spectrum disorder.

Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.