Adar null mutant mouse embryos die with aberrant double-stranded RNA (dsRNA)-driven interferon induction, and Adar Mavs double mutants, in which interferon induction is prevented, die soon after birth. Protein kinase R (Pkr) is aberrantly activated in Adar Mavs mouse pup intestines before death, intestinal crypt cells die, and intestinal villi are lost. Adar Mavs Eifak2 (Pkr) triple mutant mice rescue all defects and have long-term survival. Adenosine deaminase acting on RNA 1 (ADAR1) and PKR co-immunoprecipitate from cells, suggesting PKR inhibition by direct interaction. AlphaFold studies on an inhibitory PKR dsRNA binding domain (dsRBD)-kinase domain interaction before dsRNA binding and on an inhibitory ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA provide a testable model of the inhibition. Wild-type or editing-inactive human ADAR1 expressed in A549 cells inhibits activation of endogenous PKR. ADAR1 dsRNA binding is required for, but is not sufficient for, PKR inhibition. Mutating the ADAR1 dsRBD3-PKR contact prevents co-immunoprecipitation, ADAR1 inhibition of PKR activity, and co-localization of ADAR1 and PKR in cells.
- MeSH
- adenosindeaminasa * metabolismus genetika MeSH
- aktivace enzymů MeSH
- buňky A549 MeSH
- dvouvláknová RNA * metabolismus MeSH
- kinasa eIF-2 * metabolismus MeSH
- lidé MeSH
- myši MeSH
- proteinové domény MeSH
- proteiny vázající RNA * metabolismus genetika MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Maladaptive behaviors and interpersonal difficulties in patients with borderline personality disorder (BPD) seem connected to biased facial emotion processing. This bias is often accompanied by heightened amygdala activity in patients with BPD as compared to healthy controls. However, functional magnetic resonance imaging (fMRI) studies exploring differences between patients and healthy controls in facial emotion processing have produced divergent results. The current study explored fMRI and heart rate variability (HRV) correlates of negative facial emotion processing in patients with BPD and healthy controls. METHODS: The study included 30 patients with BPD (29 females; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 females; M = 24.66, SD = 5.28). All participants underwent the "faces" task, an emotional face perception task, in an fMRI session simultaneously with ECG. In this task, participants are presented with emotional expressions of disgust, sadness, and fear (as a negative condition) and with the same pictures in a scrambled version (as a neutral condition). RESULTS: We found no differences in brain activity between patients with BPD and healthy controls when processing negative facial expressions as compared to neutral condition. We observed activation in large-scale brain areas in both groups when presented with negative facial expressions as compared to neutral condition. Patients with BPD displayed lower HRV than healthy controls in both conditions. However, there were no significant associations between HRV and amygdala activity and BPD symptoms. CONCLUSION: The results of this study indicate no abnormal brain activity during emotional facial processing in patients with BPD. This result contrasts with previous studies and more studies are needed to clarify the relationship between facial emotion processing and brain activity in patients with BPD. Possible reasons for the absence of brain activity differences are discussed in the study. Consistent with previous findings, patients showed lower HRV than healthy controls. However, HRV was not associated with amygdala activity and BPD symptoms.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. METHODS: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. RESULTS: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. CONCLUSIONS: The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.
- Publikační typ
- časopisecké články MeSH
Objective: Body image disturbances and the attendant negative emotions are two of the major clinical symptoms of eating disorders. The objective of the present experimental study was to shed more light on the degree of association or dissociation between the physiological and emotional response to mirror exposure in patients with restrictive mental anorexia, and on the relationships between the physiological response and characteristics connected with emotional processing. Materials and Methods: Thirty adolescent girls with the restrictive type of anorexia and thirty matched healthy controls underwent bilateral measurement of skin conductance (SC) during rest, neutral stimulus exposure, and mirror exposure, and completed a set of measures focused on emotion regulation competencies, affectivity, and eating disorder pathology. Results: Compared to healthy controls, girls with restrictive anorexia rated mirror exposure as a subjectively more distressful experience. Differences in skin conductance response (SCR) were not significant; however, variance in SCR was substantially greater in the group of anorexia patients as compared to healthy controls. The overall skin conductance level (SCL) was lower in anorexia patients. Increase in SCR during mirror exposure, as opposed to exposure to neutral stimuli, was positively related to the tendency to experience negative emotions, interoceptive sensitivity, body dissatisfaction and suppression, but not to other symptoms of eating pathology or emotional awareness. A post hoc analysis suggested that physiological reactivity might be associated with interoceptive sensitivity to mirror exposure especially in anorectic patients. Conclusion: The study seems to demonstrate some degree of dissociation between psychophysiological reactivity and subjective response to body exposure in patients with restrictive anorexia. Factors affecting differences in psychophysiological responsiveness to body exposure in anorectic patients require further exploration.
- Publikační typ
- časopisecké články MeSH
Tento souborný článek představuje základní komponenty dialektické behaviorální terapie (DBT) a shrnuje dosavadní výzkumné poznatky s důrazem na jejich možné využití v klinické praxi. DBT je komplexní psychoterapeutický program pro léčbu hraniční poruchy osobnosti, který zahrnuje individuální psychoterapii, skupinový trénink dovedností, možnost telefonického koučování a pravidelná supervizní setkání terapeutů. Dosavadní studie potvrzují, že DBT vede k významné redukci sebepoškozujícího a sebevražedného chování, a je proto vhodná pro rizikové pacienty s významně vyjádřenými příznaky z tohoto okruhu. U těchto pacientů vede k behaviorální stabilizaci a umožňuje navázat další psychoterapeutickou prací v následujících fázích léčby.
This literature review presents the main components of Dialectical behavior therapy (DBT) and summarizes current research findings with an emphasis on application in clinical practice. DBT is a complex psychotherapeutic program for patients with a borderline personality disorder that consists of a combination of individual psychotherapy, skills training group, telephone coaching, and a therapist consultation team. Previous studies confirm that DBT is associated with a significant reduction of suicidal and selfharming behavior. Evidence also suggests the impact of DBT is far more pronounced in patients with severe symptoms, in which it can help achieve behavioral stabilization and makes follow-up care possible.
- MeSH
- afektivní symptomy psychologie terapie MeSH
- dialektická behaviorální terapie * MeSH
- duševně nemocní psychologie MeSH
- emoční regulace MeSH
- hraniční porucha osobnosti * psychologie terapie MeSH
- klinická studie jako téma MeSH
- komorbidita MeSH
- lidé MeSH
- sebepoškozování psychologie terapie MeSH
- sebevražda psychologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
