Schema therapy for emotional dysregulation: Theoretical implication and clinical applications

The term emotional dysregulation refers to an impaired ability to regulate unwanted emotional states. Scientific evidence supports the idea that emotional dysregulation underlies several psychological disorders as, for example: personality disorders, bipolar disorder type II, interpersonal trauma, anxiety disorders, mood disorders and posttraumatic stress disorder. Emotional dysregulation may derive from early interpersonal traumas in childhood. These early traumatic events create a persistent sensitization of the central nervous system in relation to early life stressing events. For this reason, some authors suggest a common endophenotypical origin across psychopathologies. In the last 20 years, cognitive behavioral therapy has increasingly adopted an interactiveontogenetic view to explain the development of disorders associated to emotional dysregulation. Unfortunately, standard Cognitive Behavior Therapy (CBT) methods are not useful in treating emotional dysregulation. A CBT-derived new approach called Schema Therapy (ST), that integrates theory and techniques from psychodynamic and emotion focused therapy, holds the promise to fill this gap in cognitive literature. In this model, psychopathology is viewed as the interaction between the innate temperament of the child and the early experiences of deprivation or frustration of the subject\u2019s basic needs. This deprivation may lead to develop early maladaptive schemas (EMS), and maladaptive Modes. In the present paper we point out that EMSs and Modes are associated with either dysregulated emotions or with dysregulatory strategies that produce and maintain problematic emotional responses. Thanks to a special focus on the therapeutic relationship and emotion focused-experiential techniques, this approach successfully treats severe emotional dysregulation. In this paper, we make several comparisons between the main ideas of ST and the science of emotion regulation, and we present how to conceptualize pathological phenomena in terms of failed regulation and some of the ST strategies and techniques to foster successful regulation in patients

The relationship between difficulties in emotion regulation and dysfunctional technology use among adolescents

Objectives Since two decades scientific research is studying excessive and dysfunctional new technologies use and its influences on people’s lives, in terms of personal, relational, scholastic and work functioning impairment. The objectives of the present study are to investigate gender differences in problematic new technologies use as well as to examine the relationship between problematic new technologies use, emotional regulation and its specific dimensions. Methods 280 italian adolescents (51.1% males) aged 11 to 18 years (mean age = 13.31; SD = 2.33) were recruited from two italian secondary public schools and involved in this study. Data were collected using the Internet Addiction Test, the Video Game Dependency Scale, the Brief Multicultural Version of the Test of Mobile-Phone Dependence and the Difficulties in Emotion Regulation Scale. Results Results indicate significant association between emotion dysregulation and problematic internet (r = .504; p < .001), videogame (r = .372; p < .001), mobile-phone (r = .424; p < .001) use. These results support hypothesis that adolescents with greater emotion dysregulation are more likely to experience problematic new technologies use. Additionally, stepwise multiple regression analysis pointed out that the lack of effective emotion regulation strategies is a common risk factors between the problematic new technologies use, but regression analysis highlighted specific risk factors for some of the investigated dependent behaviors. Conclusions Findings of this study highlight a link between problematic new technologies use, emotion dysregulation and its specific dimensions. The results are discussed considering scientific advances and the role of emotional dysregulation in determining problematic new technologies use in adolescence. Further research with larger sample sizes is needed to confirm our data

Attention bias dynamics and symptom severity during and following CBT for social anxiety disorder

Objective: Threat-related attention bias figures prominently in contemporary accounts of the maintenance of anxiety disorders, yet longitudinal intervention research relating attention bias to anxiety symptom severity is limited. Capitalizing on recent advances in the conceptualization and measurement of attention bias, we aimed to examine the relation between attention bias, indexed using trial-level bias scores (TLBSs) to quantify temporal dynamics reflecting dysregulation of attentional processing of threat (as opposed to aggregated mean bias scores) and social anxiety symptom severity over the course of cognitive-behavioral therapy (CBT) and 1-month follow-up. Method: Adults with social anxiety disorder (N = 39) assigned to either yohimbine-or placebo-augmented CBT completed measures of attention bias and social anxiety symptom severity weekly throughout CBT (5 sessions) and at 1-week and 1-month posttreatment. Results: TLBSs of attention bias temporal dynamics showed stronger psychometric properties than mean aggregated scores and were highly interrelated, in line with within-subject temporal variability fluctuating in time between attentional overengagement and strategic avoidance from threat. Attention bias toward threat and temporal variability in attention bias (i.e., attentional dysregulation), but not attention bias away from threat, significantly reduced over the course of CBT. Cross-lag analyses revealed no evidence of a causal relation between reductions in attentional dysregulation leading to symptom severity reduction, or vice versa. Observed relations did not vary as a function of time. Conclusions: We found no evidence for attentional dysregulation as a causal mechanism for symptom reduction in CBT for social anxiety disorders. Implications for future research are discussed

Effect of metabolic syndrome and aging on Ca2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine

BACKGROUND: Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS: Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca2+ handling dysfunction in CAD

Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival

MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over-or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics

Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects.

Organogenesis involves integration of diverse cell types; dysregulation of cell-type-specific gene networks results in birth defects, which affect 5% of live births. Congenital heart defects are the most common malformations, and result from disruption of discrete subsets of cardiac progenitor cells1, but the transcriptional changes in individual progenitors that lead to organ-level defects remain unknown. Here we used single-cell RNA sequencing to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis, revealing how dysregulation of specific cellular subpopulations has catastrophic consequences. A network-based computational method for single-cell RNA-sequencing analysis that predicts lineage-specifying transcription factors2,3 identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite the failure of right ventricular formation in Hand2-null mice4. Temporal single-cell-transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was specified but failed to properly differentiate and migrate. Loss of Hand2 also led to dysregulation of retinoic acid signalling and disruption of anterior-posterior patterning of cardiac progenitors. This work reveals transcriptional determinants that specify fate and differentiation in individual cardiac progenitor cells, and exposes mechanisms of disrupted cardiac development at single-cell resolution, providing a framework for investigating congenital heart defects

Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes.

Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant

Disordered eating behaviour is associated with blunted cortisol and cardiovascular reactions to acute psychological stress

Research suggests a potential dysregulation of the stress response in individuals with bulimia nervosa. This study measured both cardiovascular and cortisol reactions to a standardised laboratory stress task in individuals identified as showing disordered eating behaviour to determine whether dysregulation of the stress response is characteristic of the two branches of the stress response system. Female students (N = 455) were screened using two validated eating disorder questionnaires. Twelve women with disordered eating, including self-induced vomiting, and 12 healthy controls were selected for laboratory stress testing. Salivary cortisol and cardiovascular activity, via Doppler imaging and semi-automatic blood pressure monitoring, were measured at resting baseline and during and after exposure to a 10-min mental arithmetic stress task. Compared to controls the disordered eating group showed blunted cortisol, cardiac output, heart rate, and stroke volume reactions to the acute stress, as well as an attenuated vasodilatory reaction. These effects could not be accounted for in terms of group differences in stress task performance, subjective task impact/engagement, age, BMI, neuroticism, cardiorespiratory fitness, or co-morbid exercise dependence. Our findings suggest that disordered eating is characterised by a dysregulation of the autonomic stress-response system. As such, they add further weight to the general contention that blunted stress reactivity is characteristic of a number of maladaptive behaviours and states

Perceived maternal autonomy-support and early adolescent emotion regulation: a longitudinal study

This study investigated longitudinal associations between perceived maternal autonomy-supportive parenting and early adolescents' use of three emotion regulation (ER) styles: emotional integration, suppressive regulation, and dysregulation. We tested whether perceived maternal autonomy support predicted changes in ER and whether these ER styles, in turn, related to changes in adjustment (i.e., depressive symptoms, self-esteem). Participants (N= 311, mean age at Time 1 = 12.04) reported on perceived maternal autonomy support, their ER styles, and adjustment at two moments in time, spanning a one-year interval. Cross-lagged analyses showed that perceived maternal autonomy support predicted increases in emotional integration and decreases in suppressive regulation. By contrast, emotional dysregulation predicted decreases in perceived autonomy-supportive parenting. Further, increases in emotional integration were predictive of increases in self-esteem, and decreases in suppressive regulation were predictive of decreases in depressive symptoms. Together, the results show that early adolescents' perception of their mothers as autonomy-supportive is associated with increases in adaptive ER strategies and subsequent adjustment

Dysregulation of visual motion inhibition in major depression

Individuals with depression show depleted concentrations of the inhibitory neurotransmitter GABA in occipital (visual) cortex, predicting weakened inhibition within their visual systems. Yet, visual inhibition in depression remains largely unexplored. To fill this gap, we examined the inhibitory process of centersurround suppression (CSS) of visual motion in depressed individuals. Perceptual performance in discriminating the direction of motion was measured as a function of stimulus presentation time and contrast in depressed individuals (n¼27) and controls (n¼22). CSS was operationalized as the accuracy difference between conditions using large (7.5°) and small (1.5°) grating stimuli. Both depressed and control participants displayed the expected advantage in accuracy for small stimuli at high contrast. A significant interaction emerged between subject group, contrast level and presentation time, indicating that alterations of CSS in depression were modulated by stimulus conditions. At high contrast, depressed individuals showed significantly greater CSS than controls at the 66 ms presentation time (where the effect peaked in both groups). The results' specificity and dependence on stimulus features such as contrast, size and presentation time suggest that they arise from changes in early visual processing, and are not the results of a generalized deficit or cognitive bias.Accepted versio