Larry Siever

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

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

..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...

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

..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...

..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...

..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...

..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 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...

..Gene-environment interactions involving childhood maltreatment are demonstrated in recent studies on antisocial behaviors and aggressive rhesus monkeys and highlight the need for further research in this important area...

..Definitive clarification of what MDD and BPD have in common and in what ways they are distinct will only be derived from studies that examine both illnesses using the same study design and methodology...

..By adolescence, difficulties with impulsivity, aggression, acting out, and self-destructive behaviors dominate the profile...

..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 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...

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

..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...

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

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

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

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

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

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

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

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

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

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

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

..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...

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

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..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...

..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...

..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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..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...

..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...

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

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

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..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...

..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...

..These findings suggest that a subset of astrocytes localized to specific cortical layers is adversely affected in schizophrenia and raise the possibility of glutamatergic dyshomeostasis in selected neuronal populations...

..To investigate the effect of PTSD, the authors conducted a 0.5-mg DST, which is more sensitive than the 1.0-mg DST for detection of increased cortisol suppression, in a group of subjects with personality disorders...

..This line of research may refine early risk assessment and preventive mental health services...

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

..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...

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

..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...

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

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

..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)...

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

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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...

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

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

..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...

..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...

..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...

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

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

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..The proposed study will enable a better understanding of the character of serotonergic dysfunction in impulsive/aggression. ..

..Findings of heritable deficits in specific measures will be used to guide the next generation of studies of the genetics of schizophrenia. ..

..These studies will help to clarify the exact nature of this memory problem and investigate how it can be improved by medication treatment. ..

..These studies will help our understanding of an important brain chemical, serotonin, which is related to aggression, and how it is affected by antidepressants that increase serotonin. ..

..These studies will help to clarify the exact nature of this memory problem and investigate how it can be improved by medication treatment. ..

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..Once we understand the genetic architecture of these abnormalities, new medications that aim to improve the functioning and quality of life of schizophrenia patients can be developed. ..