Larry J Siever

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..Borderline personality disorder (BPD) is characterized by an inability to regulate emotional responses. The amygdala is important in learning about the valence (goodness and badness) of stimuli and functions abnormally in BPD...

..We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls...

..These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation...

..In contrast to prior SZ studies that report lower FA, individuals with SPD show sparing. Our findings are consistent with a pattern of milder thalamo-frontal dysconnectivity in SPD than schizophrenia...

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..Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD...

..These results suggest that dopamine agonists may provide benefit for the cognitive abnormalities of schizophrenia spectrum disorders...

..We report initial results from the COGS dataset of auditory N100 amplitude and gating as candidate endophenotypes...

..These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making...

..These findings provide limited support for a role of COMT in modulating aggressive behavior, and are extended to people with personality disorders...

..Exploration of the genetic architecture of specific endophenotypes may be a powerful strategy for understanding the genetic basis of schizophrenia...

..Among the schizophrenia-spectrum sample, more deficient PPI during the attended prepulses was associated with greater symptom severity as measured by the total 18-item Brief Psychiatric Rating Scale score...

..The patients activate neural networks in emotion processing that are phylogeneticall older and more reflexive than those activated by HC subjects...

..Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies...

..These findings, which are quite similar to those previously reported in patients with schizophrenia, suggest that context processing deficits are specific to the schizophrenia spectrum and are not a reflection of overall psychopathology...

..We have previously hypothesized that increased 5-HT(2A)R function in the OFC is a state phenomenon that promotes impulsive aggression...

..This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume...

..05). Findings suggest spatial working memory impairments may be a core neuropsychological deficit specific to SPD patients and highlight the role of VLPFC subcomponents in normal and dysfunctional memory performance...

..We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls...

..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...

..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...

..We evaluated the relationship of the COMT genotype with diagnostic status and cognitive performance in schizotypal personality disorder...

..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 affect-modulated startle response is a reliable indicator of emotional processing of stimuli. The aim of this study was to examine emotional processing in BPD patients (n = 27) and healthy control subjects (n = 21)...

..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...

..Most of these findings have been generated from inpatient clinical samples...

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..The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD...

..Dysfunctional FST activation, particularly in the caudate may underlie PPI abnormalities in schizophrenia-spectrum patients...

..62; 95% CI = 1.19-2.21) associated with the disorder. The association remained significant after correction for multiple testing. Our data support the hypothesis that genetic variations in ADAMTS12 influence the risk of schizophrenia...

..low-dose responders. Evaluation of models of "serotonergic-responsive" and norepinephrine-responsive" depression requires larger numbers of patients...

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..This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD...

..We hypothesized that SPD patients would demonstrate comparable or lower DA and HPA responses after 2-DG to HV...

..The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function...

..Results from these analyses also lend support to a large body of work that demonstrates that normal and abnormal personality features are related...

..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...

..One possible contributing factor to emotional instability is a failure to adequately employ adaptive cognitive regulatory strategies such as psychological distancing...

..Indeed, SPD subjects comprise the only group not statistically different from schizophrenic patients in quantitative or qualitative ratings...

..The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum...

..These findings implicate abnormalities of the NF-κB signaling pathway in SZ and provide evidence for an additional possible mechanism affecting the translocation of NF-κB signaling to the nucleus...

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..The authors discuss the implications of these processing capacity limitations for understanding both the signature of cognitive impairment within the schizophrenia spectrum and general abnormalities in working memory...

..The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms...

..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...

..In Part II, we will illustrate the clinical application of the model with vignettes of patients with varying degrees of personality psychopathology, to show how assessments might be conducted and diagnoses reached...

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..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...

..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...

..Our findings argue against the hypothesis that 5-HT2cR editing efficiency is regulated by extracellular serotonin levels...

..This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD...

..These findings are consistent with altered PKC and BDNF activity in a range of neuropsychiatric conditions including bipolar disorder, depression and suicide...

..In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment...

..The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment...

..Preliminary trials of catecholaminergic agents suggest that these agents may be able to improve these impaired cognitive functions...

..Preclinical and human studies suggest that the orbital frontal cortex and anterior cingulate cortex play an inhibitory role in the regulation of aggression...

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..No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation...

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..Side effects were generally well tolerated, and there was no group difference in dropout rate for side effects. CONCLUSION: Low-dose risperidone appears to be effective in reducing symptom severity in SPD and is generally well tolerated...

..Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients...

..Increasing efforts to translate personality theory and social cognitive neuroscience into increasingly specific neurobiological substrates may provide more effective targets for pharmacotherapy...

..A pathophysiological model of the relationship between schizotypal personality disorder and schizophrenia was developed based on this data...

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..In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia...

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..Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was approximately 50% of that observed for the full-length isoform...

..Thus, an endophenotypic approach not only provides clues to underlying candidate genes contributing to these behavioral dimensions, but may also point the way to a better understanding of pathophysiological mechanisms...

..The authors examined the relationship of borderline personality disorder to posttraumatic stress disorder (PTSD) with respect to the role of trauma and its timing...

..Although there are a number of competing models of personality structure, they have remarkable convergence on a set of three to five basic personality dimensions...

..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...

..The use of laboratory paradigms for measures of aggression and affective instability are discussed in the context of such endophenotypic approaches...

..These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies...

..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...

..These findings suggest that it is possible to detect both auditory and visual processing episodic memory abnormalities in the spectrum and that these deficits are uniformly a function of verbal working memory impairments...

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..Moreover, working memory deficits can be ameliorated by treatments that augment D(1) receptor stimulation, indicating that this target presents a unique opportunity for the restoration of cognitive function in schizophrenia...

..Both dimensions could account for the stress reactivity of bipolar patients that may lead to relapses...

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..Context processing was strongly associated with working memory and selective attention performance in the SPD individuals...