Dataset Information

Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder.

ABSTRACT: Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which poses a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD.We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional brain imaging. Thirty-eight BPD patients with intermittent explosive disorder (BPD-IED) and 36 age-matched healthy control subjects (HCs) received (18)fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) on two occasions with a provocation and nonprovocation version of the PSAP. Mean relative glucose metabolism was measured throughout the cortex, and difference scores (provoked - nonprovoked) were calculated. A whole brain exploratory analysis for the double difference of BPD-IED - HC for provoked - nonprovoked was also conducted.BPD-IED patients were significantly more aggressive than HCs on the PSAP. BPD-IED patients also increased relative glucose metabolic rate (rGMR) in OFC and amygdala when provoked, while HCs decreased rGMR in these areas. However, HCs increased rGMR in anterior, medial, and dorsolateral prefrontal regions during provocation more than BPD-IED patients.Patients responded aggressively and showed heightened rGMR in emotional brain areas, including amygdala and OFC, in response to provocation but not in more dorsal brain regions associated with cognitive control of aggression. In contrast, HCs increased rGMR in dorsal regions of PFC during aggression provocation, brain regions involved in top-down cognitive control of aggression, and, more broadly, of emotion.

SUBMITTER: New AS

PROVIDER: S-EPMC2788117 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder.

New Antonia S AS Hazlett Erin A EA Newmark Randall E RE Zhang Jane J Triebwasser Joseph J Meyerson David D Lazarus Sophie S Trisdorfer Roanna R Goldstein Kim E KE Goodman Marianne M Koenigsberg Harold W HW Flory Janine D JD Siever Larry J LJ Buchsbaum Monte S MS

Biological psychiatry 20090912 12

<h4>Background</h4>Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which poses a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD.<h4>Methods</h4>We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional b ...[more]

PMID: 19748078

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Project description:Introduction: Aggressive behavior is highly prevalent in patients with borderline personality disorder (BPD) and represents a major burden for patients and their environment. Previous studies have hypothesized threat hypersensitivity, among other mechanisms, as a biobehavioral mechanism underlying aggressive behavior in patients with BPD. The effects of a 6-week mechanism-based anti-aggression psychotherapy (MAAP) for the group setting were tested in comparison to the effects of a non-specific supportive psychotherapy (NSSP) on this hypothesized mechanism and their relation to the effects on aggressive behavior. Methods: To assess mechanisms of reactive aggression, 38 patients with BPD (20 in MAAP and 18 in NSSP) and 24 healthy controls participated in an emotion classification task before and after therapy or at a similar interval of 7 weeks for controls, respectively. In addition, current reactive aggressive behavior was assessed by the externally directed overt aggression score of the Overt Aggression Scale Modified (OAS-M) at both time points. Mixed linear models were used to test for group differences and differential treatment effects. Results: Consistent with previous findings, patients showed longer response latencies and misclassified faces as angry more often than healthy controls. Comparing pre- and post-treatment measurements, the MAAP group showed an increase in response latency in classifying angry faces, whereas the NSSP group showed a decrease in latency. Furthermore, the difference between pre- and post-treatment response latencies in classifying emotional faces correlated with the reductions in reactive aggression in the MAAP group, but not in the NSSP group or healthy controls. Conclusion: The results suggest an impact of MAAP on threat sensitivity as well as cognitive control, which has also been previously hypothesized as a biobehavioral mechanism underlying reactive aggression in patients with BPD. In addition, our findings shed light on the importance of these two biobehavioral mechanisms underlying reactive aggression as mechanisms of change addressed by MAAP. Further studies are needed to determine whether the behavioral change is stable over time and to what extent this change is related to a stable reduction in reactive aggression in a larger group of patients with BPD.

Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder.

Publications

Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder.

Similar Datasets

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