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Biological and pharmacological aspects of borderline personality disorder.

Biological and psychopharmacological research focusing on patients with a DSM-III-R diagnosis of borderline personality disorder suggests that the disorder may encompass three clusters of symptoms--affective instability, transient psychotic phenomena, and impulsive aggressive behavior--that have different underlying biological substrates that respond to different classes of pharmacological agents. Affective instability, which may be related to abnormalities in the brain's adrenergic and cholinergic systems, appears to respond to agents such as lithium and carbamazepine that are effective in treating major affective disorders. Abnormalities in central dopaminergic systems may underlie transient psychotic symptoms. This relationship is consistent with reports of beneficial effects of low-dose neuroleptics in treating some borderline patients. Abnormalities in central nervous system serotonergic functioning appear to underlie impulsive aggressive behaviors. These behaviors may respond to serotonergic agents such as fluoxetine.

Borderline Personality Disorder↗

Positive and negative schizotypy in a student sample: neurocognitive and clinical correlates.

Positive and negative schizotypy may represent discrete factors or dimensions. To determine if distinct neurocognitive profiles are associated with these dimensions or factors, we classified university students on the basis of positive and negative schizotypal symptoms and conducted separate analyses. Following prior work in the neuropsychiatric literature, we predicted that subtle prefrontal deficits would be selectively associated with negative schizotypal personality features in a nonclinical student sample. We also investigated the relationship between positive/negative schizotypy and associated clinical states or personality dimensions including antisocial personality disorder, obsessive-compulsive personality traits, generalized and social anxiety, empathy, and impulsivity. Classification of subjects into positive and negative schizotypy groups revealed distinct neurocognitive and clinical profiles. We observed a positive relation between measures of temporolimbic dysfunction, impulsivity, antisocial behavior, and positive schizotypal phenomena. Negative schizotypy was associated with subtle performance deficits on measures of frontal executive function, increased social anxiety, and obsessive-compulsive phenomena. Findings are consistent with the contention that positive and negative schizotypy represent discrete factors.

Adolescent↗

Intermittent explosive disorder-revised: development, reliability, and validity of research criteria.

The study of human aggression has been hindered by the lack of reliable and valid diagnostic categories that specifically identify individuals with clinically significant displays of impulsive aggressive behavior. DSM intermittent explosive disorder (IED) ostensibly identifies one such group of individuals. In its current form, IED suffers from significant theoretical and psychometric shortcomings that limit its use in clinical or research settings. This study was designed to develop a revised criteria set for IED and present initial evidence supporting its reliability and validity in a well characterized group of personality disordered subjects. Accordingly, research criteria for IED-Revised (IED-R) were developed. Clinical, phenomenologic, and diagnostic data from 188 personality disordered individuals were reviewed. IED-R diagnoses were assigned using a best-estimate process. The reliability and construct validity of IED-R were examined. IED-R diagnoses had high interrater reliability (kappa = .92). Subjects meeting IED-R criteria had higher scores on dimensional measures of aggression and impulsivity, and had lower global functioning scores than non-IED-R subjects, even when related variables were controlled. IED-R criteria were more sensitive than DSM-IV IED criteria in identifying subjects with significant impulsive-aggressive behavior by a factor of four. We conclude that in personality disordered subjects, IED-R criteria can be reliably applied and appear to have sufficient validity to warrant further evaluation in field trials and in phenomenologic, epidemiologic, biologic, and treatment-outcome research.

Adult↗

Positron emission tomography of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without borderline personality disorder.

Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.

Adult↗

The prey-dependent consumption two-prey one-predator models with stage structure for the predator and impulsive effects.

In this paper, we consider the prey-dependent consumption two-prey one-predator models with stage structure for the predator and impulsive effects. By applying the Floquet theory of linear periodic impulsive equation, we show that there exists a globally asymptotically stable pest-eradication periodic solution when the impulsive period is less than some critical value, that is, the pest population can be eradicated totally. But from the point of ecological balance and saving resources, we only need to control the pest population under the economic threshold level instead of eradicating it totally, and thus, we further prove that the system is uniformly permanent if the impulsive period is larger than some critical value, and meanwhile we also give the conditions for the extinction of one of the two preys and permanence of the remaining species. Thus, we can use the stability of the positive periodic solution and its period to control insect pests at acceptably low levels. Considering population communities always are imbedded in periodically varying environments, and the parameters in ecosystem models may oscillate simultaneously with the periodically varying environments, we add a forcing term into the prey population's intrinsic growth rate. The resulting bifurcation diagrams show that with the varying of parameters, the system experiences process of cycles, periodic windows, periodic-doubling cascade, symmetry breaking bifurcation as well as chaos.

Animals↗

Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression.

BACKGROUND: Suicide and depressive disorders are strongly associated, yet not all depressed patients commit suicide. Genetic factors may partly explain this difference. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene and its 5' upstream region may predispose to suicide in major depressive disorder (MDD) and whether this predisposition is mediated by impulsive-aggressive behaviors (IABs). METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide while depressed. Phenotypic assessments were carried out by means of proxy-based interviews. Single-marker and haplotype association analyses were conducted. Differences in behavioral and personality traits according to genotypic variation were investigated, as well as genetic and clinical predictors of suicide. RESULTS: We found two upstream and two intronic SNPs associated with suicide. No direct effect of these variants was observed on IABs. However, a slight association with reward dependence scores was found. Controlling for suicide risk factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide, along with cluster B personality disorders and family history of suicide. CONCLUSIONS: The TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in MDD; however, our findings do not support the role of IABs as mediators.

Adolescent↗

Modification of impulsive tempo in learning-disabled pupils.

Thirty-three impulsive learning-disabled males, aged 9-12 years, were assigned to one of three treatment conditions: (a) Modeling, in which subjects were exposed to a videotape of a boy demonstrating reflective problem-solving activities and instructing himself to perform cautiously; (b) Modeling Plus Self-Verbalization, in which subjects observed the same videotape and were additionally required to verbalize similar reflective instructions; and (c) Control, in which subjects were shown a videotape of the task materials used in the modeling videotape, but without the model. Subjects were tested immediately after exposure to treatment, and again 3 weeks later, on different forms of the Matching Familiar Figures test. Both Modeling and Modeling Plus Self-Verbalization conditions were superior to Control in reducing errors on the immediate test, but the three treatments did not differ on the delayed test. No significant differences among the three conditions were found with regard to response latency. Discrepancies between the present results and those of previous related studies were noted, and potential research directions were suggested.

Behavior Therapy↗

Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.

Adult↗

Insular dopamine D2 receptors and novelty seeking personality in Parkinson's disease.

Novelty seeking is a temperament trait characterized by impulsiveness and exploratory behavior. Dopamine has been suggested to be the primary neurotransmitter modulator of novelty seeking, and in young healthy subjects, a correlation between increased novelty seeking and decreased insular cortical dopamine D2 receptor availability has been reported. The proposed link between dopamine deficiency and reduction in novelty seeking in Parkinson's disease is controversial. The present study examined whether a link between insular D2 receptor availability and novelty seeking can be replicated in Parkinson's disease patients. [11C]FLB 457 positron emission tomography imaging was carried out in 28 patients with Parkinson's disease, and the data were analyzed using voxel-based statistical analysis. The results demonstrated a negative correlation between the novelty seeking score and the dopamine D2 availability bilaterally in the insular cortex (corrected P=0.001; r=-0.74 [right hemisphere]; r=-0.66 [left hemisphere]). The results provide further support for a relationship between novelty seeking and insular D2 receptors. They indicate that the association is cross-cultural, independent of age, and unaffected by dopaminergic degeneration.

Aged↗

Are children reliable reporters?

Fifty children, ranging in age from 6 to 16 years, and their mothers were interviewed using the same structured interview, which in its content follows the usual psychiatric examination of a child. Their answers were compared and it was found that there was an 80% average agreement on all questions. The agreement (between child and parent) was highest on questions relating to factual information (84%) and the agreement (between child's interviewer and parent) was lowest in the section dealing with mental status (69%). Girls were more reliable informants than boys.

Adolescent↗

Decision-making in obesity: a study using the Gambling Task.

The present study addresses the issue of whether a "decision-making disorder" could account for the behavioral problems of severely obese patients (BMI score >34) who are not classified by traditional psychiatric Eating Disorder tests. The neuropsychological test employed, the Gambling Task (GT), is not directly related to the food domain, but it is sensitive to failure in making long-term advantageous choices. A comparison was made of 20 obese subjects (OS) and 20 normal-weight subjects (NWS) matched in age, education and IQ. The subjects' personalities and food behavior were assessed from psychological questionnaires, and then the Gambling Task was administered. The number of "good" choices made by the two groups during GT performance differed significantly, and the OS did not learn to maximize advantageous choices like the NWS did. OS behavior could be consistent with a prefrontal cortex defect that implies difficulties in inhibition of excessive food intake.

Adult↗

The assessment of binge eating severity among obese persons.

The purpose of this study was to conduct an assessment of binge eating severity among obese persons. Two questionnaires were developed. A 16-item Binge Eating Scale was constructed describing both behavioral manifestations (e.g., eating large amounts of food) and feeling/cognitions surrounding a binge episode (e.g., guilt, fear of being unable to stop eating). An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating: the tendency to set unrealistic standards for a diet (e.g., eliminating "favorite foods") and low efficacy expectations for sustaining a diet. The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no, moderate or severe binge eating problems. Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet. The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating.

Adult↗

Neuropsychological and psychosocial function in children with a history of snoring or behavioral sleep problems.

OBJECTIVES: To compare neuropsychological and psychosocial function in children with a history of snoring, children with a history of behavioral sleep problems (BSP), children with both a history of snoring and BSP, and a group of control subjects. STUDY DESIGN: Families awaiting consultation for "sick" visits in 5 general practice clinics completed the Sleep Disturbance Scale for Children. A subset of children were categorized into groups: Snorers (n = 11), BSP (n = 13), Snorers+BSP (n = 9), and controls (n = 31). Children underwent psychological (Wechsler Abbreviated Scale of Intelligence, Children's Memory Scale; Test of Everyday Attention and Auditory Continuous Performance Test) and psychosocial assessment (Child Behavior Checklist). RESULTS: With analysis of variance, it was revealed that, compared with children in the BSP and control groups, those in the Snorers+BSP and Snorers groups showed reduced intelligence and attention scores. By contrast, compared with children in the Snorers and control groups, children in the Snorers+BSP and BSP groups reported reduced social competency, increased problematic behavior, and reduced memory scores. Children in the combination of Snorers+BSP group showed more deficits than children in all other groups. CONCLUSION: In children, snoring and BSP, separately and together, are associated with impaired neuropsychological and psychosocial functioning. Furthermore, snoring and BSP are related to performance in disparate ways. Snoring was associated with intelligence and attention deficits, whereas BSP was associated with memory and behavioral deficits.

Adolescent↗

Sydenham's chorea.

Sydenham's chorea (SC) is a disorder of the central nervous system (CNS) characterized by sudden, involuntary, arrhythmic, clonic, and purposeless movements. SC appears to provide a model for understanding various neuropsychiatric dysfunctions. Its relationship with attentional deficits, obsessive-compulsive symptoms (OCS) as well as movement disorders provides support for the hypothesis of the involvement of the corticostriatal loops in the pathophysiology of the disorder.

Autoimmune Diseases↗

Gray's reinforcement sensitivity model and child psychopathology: laboratory and questionnaire assessment of the BAS and BIS.

The Behavioral Approach System (BAS) and Behavioral Inhibition System (BIS) are widely studied components of Gray's sensitivity to reinforcement model. There is growing interest in integrating the BAS and BIS into models of risk for psychopathology, however, few measures assess BAS and BIS functioning in children. We adapted a questionnaire measure and reaction time task from adult studies to assess the BAS and BIS in a sample of 9-12 year olds (N = 63; 42% female). A continuous performance task was also administered to assess physiological correlates of the BAS and BIS. Factor analysis supported 3 subdimensions of the BAS (Drive, Reward Responsivity, and Impulsivity/Fun seeking), and one dimension of the BIS (sensitivity to punishment). Results supported the utility of the questionnaire measures and reaction time task as assessments of BAS and BIS functioning. Moreover, these measures were associated with internalizing and externalizing problem behavior as expected. High levels of impulsivity/fun seeking, but not drive or reward responsivity, were associated with high levels of externalizing problems, whereas high levels of sensitivity to punishment were associated with high levels of internalizing behavior problems. The relation between physiological indices and caregiver reports of the BAS, BIS, and problem behavior were complex and not consistent with expectation.

Child↗