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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.

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.

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.

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.

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.

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

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.

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 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.

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.

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.

OBJECTIVE: The serotonin system is believed to play a role in modulating impulsivity and violence. Previous imaging studies have implicated the anterior cingulate and orbitofrontal cortex in impulsive aggression. This study evaluated regional serotonin transporter distribution in the brain of individuals with impulsive aggression by using positron emission tomography (PET) with the serotonin transporter PET radiotracer [(11)C]McN 5652. METHOD: Ten individuals with impulsive aggression and 10 age- and sex-matched healthy comparison subjects underwent [(11)C]McN 5652 PET. All individuals were medication free at the time of scanning. Regional total distribution volumes were derived by using a one-tissue compartment kinetic model with arterial input function. Outcome measures of serotonin transporter availability included the binding potential and the specific-to-nonspecific partition coefficient (V(3)''). RESULTS: Serotonin transporter availability was significantly reduced in the anterior cingulate cortex of individuals with impulsive aggression compared with healthy subjects, as noted by differences in both binding potential (mean=3.1 ml/g [SD=1.9] versus 5.0 ml/g [SD=2.0], respectively) and V(3)'' (mean=0.15 [SD=0.09] versus 0.26 [SD=0.09]). In other regions examined, serotonin transporter density was nonsignificantly lower in individuals with impulsive aggression compared with healthy subjects. CONCLUSIONS: Pathological impulsive aggressivity might be associated with lower serotonergic innervation in the anterior cingulate cortex, a region that plays an important role in affective regulation.

Background. Functional MRI studies have begun to identify neural networks implicated in visuospatial working memory in healthy volunteers and patients with schizophrenia. The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum. Method. Unmedicated patients with SPD by DSM-IV criteria and normal controls were assessed with fMRI while performing a visuospatial working-memory task. It required the subjects to retain the location of three dots located on the circumference of an imaginary circle and then respond to a query display in which one dot was presented and the subject required to press a button to indicate whether the probe dot location was previously displayed. Subject groups did not differ significantly in spatial memory scores. The exact Talairach and Tournoux coordinates of brain areas previously reported to show activation with spatial memory tasks were assessed. Results. The majority of these locations showed BOLD response activation significantly less in patients during the memory retention period, including the left ventral prefrontal cortex, superior frontal gyrus, intraparietal cortex and posterior inferior gyrus. Regions in the right middle prefrontal and prestriate cortex showed greater activation at a trend level for patients with SPD than for normal controls. In addition, we replicated the findings of increased activation with the task in healthy volunteers in the premotor areas, ventral prefrontal cortex and parietal cortex. Conclusions. SPD patients show decreased activation compared to healthy volunteers in key frontal regions and we also provided a partial replication of findings reported in healthy subjects.

Background : The cingulate gyrus, which is involved in affect, attention, memory and higher executive functions, has been implicated as a dysfunctional region in schizophrenia. Postmortem studies report cytoarchitectural changes in the anterior cingulate gyrus (ACG) and functioning imaging studies show correlations between the degree of hypometabolism of the anterior cingulate and clinical symptoms in schizophrenia. Methods : Unmedicated patients with schizophrenia ( n =27) and schizotypal personality disorder (SPD) ( n =13), as well as sex- and age-matched control subjects ( n =32), were studied with 18 F-fluorodeoxyglucose positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As a control over mental activity, all subjects performed a verbal working memory task during the PET protocol. The cingulate gyrus was first outlined on the MRI scans and, after coregistration, the coordinates were applied to the PET scans to yield a three-dimensional metabolic map of the cingulate gyrus for each subject. A statistical resampling method was used to analyze the metabolic differences between groups. Results : Compared with controls, patients with schizophrenia had lower relative glucose metabolic rates in the left anterior cingulate and the right posterior cingulate gyrus (PCG) assessed by 3-D significance probability mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left posterior cingulate than did controls. Furthermore, volumetric measurement with MRI showed the left anterior cingulate and Brodmann area 24′ to be smaller in schizophrenic patients than controls. Conclusions : Compared with controls, patients with schizophrenia have metabolic and volumetric reductions in a cingulate gyrus area that is related to higher executive functions. Schizotypal patients rely more on sensory association areas to perform a cognitive task than do controls and seem to be a group that is partially distinct in its physiological and functional characteristics.

To examine the prolactin (prl) response to d,l-fenfluramine in a large sample of personality disorder patients with impulsive aggression. Patients were screened from clinics at the Bronx VAMC and the Mount Sinai Medical Center and from press releases. One hundred and forty-six personality disorder patients (90M;56F) and 23 normal controls (15M;8F) underwent oral d,l-fenfluramine challenge. The peak change in prolactin(deltapkprl) was calculated by subtracting baseline prolactin from peak response following fenfluramine administration (3 h). Analysis of variance and regression analysis were used to detect group differences in deltapkprl. Deltapkprl in impulsive aggressive men, but not women, with personality disorders was blunted compared with controls. Men with suicide histories also had a blunted deltapkprl compared with those without, which was not accounted for by depression. This study represents a replication of previous studies, in a much larger sample, showing a blunted PRL response to fenfluramine of male patients with personality disorder in relation to impulsive aggression and to suicide attempts.

Background:This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174).Methods:Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure.Results:A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21–.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores.Conclusion:This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder.

Background:Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples.Methods:This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution.Results:Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men.Conclusion:These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder.

Objective: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. Method: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. Results: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. Conclusions: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with schizophrenia.

Objective: Schizotypal personality disorder (SPD) has many phenomenological, genetic, physiologic, and neuroanatomical commonalities with schizophrenia. Patients with the disorder often suffer from marked social and occupational impairment, yet they have been difficult to treat with medications because of their unusual sensitivity to side effects. This study was designed to determine whether low-dose risperidone treatment is acceptable to SPD patients and can reduce characteristic schizotypal symptoms. In addition, if SPD patients respond to an antipsychotic medication, this will provide support for the notion of a commonality in treatment response between SPD and schizophrenia. Method: Twenty-five patients with DSM-IV-defined SPD were entered into a 9-week randomized, double-blind, placebo-controlled study of low-dose risperidone (starting dose of 0.25 mg/day, titrated upward to 2 mg/day) in the treatment of SPD. Patients were rated with the Positive and Negative Syndrome Scale (PANSS), the Schizotypal Personality Disorder Questionnaire, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from 1995 to 2001. Results: The subjects had a low incidence of depression and of comorbid borderline personality disorder. Patients receiving active medication had significantly (p

Objective: Dissociative phenomena exist on a spectrum ranging from psychological absorption to highly symptomatic disruptions of identity and memory. A statistical methodology called taxometric analysis has established a set of indicators that identify patients who have pathological dissociation, a qualitatively different form of dissociative phenomena. Using taxometric methodology, this study examines the relationship of pathological dissociation to personality diagnosis and self-directed injury, including suicide and history of childhood abuse, in a sample of outpatients with personality disorders. Method: Patients were recruited from advertisements or referred from local clinicians. Participants completed a diagnostic interview and rating scales for dissociation, self-injury and childhood trauma. Pathological dissociation was identified using the Dissociative Experiences Scale-Taxon (DES-T; Waller, Putnam, & Carlson, 1996). Membership in the pathological dissociation taxon was established by c...

This study sought to understand affective instability among patients with borderline personality disorder by examining the degree of instability in six affective domains. The authors also examined the subjective intensity with which moods are experienced and the association between instability and intensity of affect.In a group of 152 patients with personality disorders, subjective affective intensity and six dimensions of affective instability were measured. The mean scores for lability and intensity for each affective domain for patients with borderline personality disorder were compared with those of patients with other personality disorders through analyses that controlled for other axis I affective disorders, age, and sex.Greater lability in terms of anger and anxiety and oscillation between depression and anxiety, but not in terms of oscillation between depression and elation, was associated with borderline personality disorder. Contrary to expectation, the experience of an increase in subjective affective intensity was not more prominent in patients with borderline personality disorder than in those with other personality disorders.By applying a finer-grained perspective on affective instability than those of previous personality disorder studies, this study points to patterns of affective experience characteristic of patients with borderline personality disorder.