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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.

Recent initiatives in the empirically based classification of psychopathology, namely, the Hierarchical Taxonomy of Psychopathology (HiTOP), have made significant strides in addressing the limitations of traditional taxonomies (i.e.

Previous research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD. To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD. We used positron emission tomography with [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory. There were no significant group differences in BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND in several striatal subregions. In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.

Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in the neurobiology of schizophrenia. Comparing thalamic connectivity in SPD and schizophrenia could reveal an intermediate schizophrenia-spectrum phenotype to elucidate neurobiological risk and protective factors in psychosis. We used rsfMRI to investigate functional connectivity between the mediodorsal nucleus (MDN) and pulvinar, and their connectivity with frontal and temporal cortical regions, respectively in 43 healthy controls (HCs), and individuals in the schizophrenia-spectrum including 45 psychotropic drug-free individuals with SPD, and 20 individuals with schizophrenia-related disorders [(schizophrenia (n = 10), schizoaffective disorder (n = 8), schizophreniform disorder (n = 1) and psychosis NOS (n = 1)]. Individuals with SPD had greater functional connectivity between the MDN and pulvinar compared to individuals with schizophrenia. Thalamo-frontal (i.e., between the MDN and rostral middle frontal cortex) connectivity was comparable in SPD and HCs; in SPD greater connectivity was associated with less symptom severity. Individuals with schizophrenia had less thalamo-frontal connectivity and thalamo-temporal (i.e., pulvinar to the transverse temporal cortex) connectivity compared with HCs. Thalamo-frontal functional connectivity may be comparable in SPD and HCs, but abnormal in schizophrenia, and that this may be protective against psychosis in SPD.

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.

Objective We examined gender differences and similarities in aggression, impulsivity, suicidal behaviour, and psychiatric comorbidity in men and women with borderline personality disorder (BPD) compared with healthy controls. Method A community sample of 511 participants (healthy controls: 81 men and 82 women; BPD patients: 145 men and 203 women) were rigorously characterized using structured diagnostic interviews and symptom severity assessments. Results In comparison with women with BPD, men were less educated, had higher total Barratt Impulsivity Scale (BIS), BIS-motoric impulsiveness and BIS-non-planning impulsiveness subscale, total Buss-Perry Aggression Questionnaire (BPAQ), and BPAQ-physical aggression subscale scores. Men with BPD were more likely to have comorbid narcissistic, antisocial, paranoid, and schizotypal personality disorders, alcohol and substance use disorders but less likely to have dependent and obsessive-compulsive personality disorders compared to women with BPD. There was a trend toward higher maximum lethality of suicide attempts in men suicide attempters compared with women suicide attempters but no difference between men and women with regard to the proportion of suicide attempters or the number of suicide attempts. Conclusion Men with BPD are more impaired and may be at higher risk of dying by suicide compared to women with BPD.

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.

Abnormalities in temporal and frontal cortical volume, white matter tract integrity, and hemispheric asymmetry have been implicated in schizophrenia-spectrum disorders. Schizotypal personality disorder can provide insight into vulnerability and protective factors in these disorders without the confounds associated with chronic psychosis. However, multimodal imaging and asymmetry studies in SPD are sparse. Thirty-seven individuals with SPD and 29 healthy controls (HC) received clinical interviews and 3 T magnetic resonance T1-weighted and diffusion tensor imaging scans. Mixed ANOVAs were performed on gray matter volumes of the lateral temporal regions involved in auditory and language processing and dorsolateral prefrontal cortex involved in executive functioning, as well as fractional anisotropy (FA) of prominent white matter tracts that connect frontal and temporal lobes. In the temporal lobe regions, there were no group differences in volume, but SPD had reduced right > left middle temporal gyrus volume asymmetry compared to HC and lacked the right > left asymmetry in the inferior temporal gyrus volume seen in HC. In the frontal regions, there were no differences between groups on volume or asymmetry. In the white matter tracts, SPD had reduced FA in the left sagittal stratum and superior longitudinal fasciculus, and increased right > left asymmetry in sagittal stratum FA compared to HC. In the SPD group, lower left superior longitudinal fasciculus FA was associated with greater severity of disorganization symptoms. Findings suggest that abnormities in structure and asymmetry of temporal regions and frontotemporal white matter tract integrity are implicated in SPD pathology.

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.

Borderline personality disorder (BPD) is complex and its phenomenology is hard to define, contributing to the view that it is not a “real” disorder. Yet increasingly powerful research suggests that it is both “real” and disabling, with high morbidity and even mortality. A review of the disorder’s history helps to shed light on the possible confusion surrounding the diagnosis and also provide insight into what has been consistently observed through different iterations of the disorder. The term “borderline personality disorder” has its origins in decades-old responses to a then bewildering, previously unrecognized patient population. This chapter presents the history of the name “borderline personality disorder” as well as historical case descriptions of individuals with symptoms that currently would be classified as BPD. It also considers the implications of the reclassification of “personality disorders” in DSM-5 into “Section 2” alongside disorders that have to date been placed on Axis I.

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.

Recent research findings have contributed to an improved understanding and treatment of borderline personality disorder. This disorder is characterised by severe functional impairments, a high risk of suicide, a negative effect on the course of depressive disorders, extensive use of treatment, and high costs to society. The course of this disorder is less stable than expected for personality disorders. The causes are not yet clear, but genetic factors and adverse life events seem to interact to lead to the disorder. Neurobiological research suggests that abnormalities in the frontolimbic networks are associated with many of the symptoms. Data for the effectiveness of pharmacotherapy vary and evidence is not yet robust. Specific forms of psychotherapy seem to be beneficial for at least some of the problems frequently reported in patients with borderline personality disorder. At present, there is no evidence to suggest that one specific form of psychotherapy is more effective than another. Further research is needed on the diagnosis, neurobiology, and treatment of borderline personality disorder.

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.