Dysregulation Domains Research Articles

Global analysis of gene expression in response to double trisomy loquat (Eriobotrya japonica)

Aneuploidy generally has severe phenotypic consequences. However, the molecular basis for this has been focused on single chromosomal dosage changes. It is not clear how the karyotype of complex aneuploidies affects gene expression. Here, we identified six different double-trisomy loquat strains from Q24 progenies of triploid loquat. The differences and similarities of the transcriptional responses of different double trisomy loquat strains were studied systematically via RNA-seq. The global modulation of gene expression indicated that both cis and trans-effects coordinately regulated gene expression in aneuploid loquat to some extent, and this coordinated regulation was determined by different gene functional groups. Aneuploidy can induce specific transcriptional responses on loquat chromosomes. The differentially expressed genes exhibited regional gene expression dysregulation domains along chromosomes. Furthermore, Aneuploidy could also promote the expression of genes with moderate and high in loquats. Our results provide new insights into the genome-wide transcriptional effects of karyotypes with complex aneuploidies.

Food addiction and binge eating disorder are linked to shared and unique deficits in emotion regulation among female seeking bariatric surgery

BackgroundProblematic eating behaviors can indicate obesity-related problems. Food addiction (FA) is not classified as an official diagnosis. However, given the many commonalities between FA and binge-eating disorder (BED) within the context of obesity, it is imperative to conduct a comparative investigation. The current study aimed to identify overlapping and distinctive features in emotion dysregulation as an underlying mechanism and emotional eating as a clinical feature among four groups of females with obesity seeking bariatric surgery.MethodsData on emotion dysregulation and emotional eating were derived from the total 128 Females with obesity seeking bariatric surgery (Mage = 38.91 ± 10.59, MBMI = 42.10 kg/m2 ± 4.43) divided into four groups: those with FA (n = 35), BED (n = 35), BED + FA (n = 31) and a control group of individuals with obesity only (OB; n = 27), using well-established measures.ResultsRegarding descriptive statistics, the BED + FA group showed the highest levels of emotional dysregulation (M = 111.09) and emotional eating (M = 46.80), while the OB group acquired the lowest scores (M = 70.44 and M = 27.29, respectively). Univariate analyses of variance revealed significant differences between the four groups in terms of emotion dysregulation F(3, 124) = 24.63, p < .01 and emotional eating F(3, 124) = 26.26, p < .01. All of the emotion dysregulation domains revealed significant differences too. Pairwise comparisons using Bonferroni post hoc tests did not reveal any significant differences between BED + FA and BED groups, while all of our other hypotheses regarding this matter were confirmed.ConclusionsThe study found that individuals with obesity and comorbid BED exhibit greater emotional dysregulation compared to those with OB or FA, indicating a need to assess BED in individuals with obesity. Emotion dysregulation may be linked to increased BED and FA, but those with BED seem more affected by limited access to emotion regulation strategies. These findings support the notion that PEBs are associated with emotion dysregulation and underscore the need for tailored interventions that target emotion regulation skills before and after bariatric surgery.

Emotional Dysregulation in Mild Behavioral Impairment Is Associated with Reduced Cortical Thickness in the Right Supramarginal Gyrus.

Mild behavioral impairment (MBI) has attracted attention as a possible precursor symptom of dementia, but its neural basis has not been fully investigated. We aimed to investigate the relationship between MBI and surface area, cortical thickness, and volume in the temporal and parietal lobes, which are strongly associated with dementia and emotional disorders. This retrospective study evaluated 123 participants: 90 with mild cognitive impairment (MCI), 13 with subjective cognitive decline (SCD), and 20 cognitively healthy (CH). Using analysis of covariance (ANCOVA) with sex, age, and MMSE score as covariates, cortical thickness, surface area, and volume in 10 regions were compared between groups with and without MBI. Groups with MBI emotional dysregulation were also compared with groups without MBI. ANCOVA revealed significantly smaller cortical thickness in the MBI group's right parahippocampal (p = 0.01) and supramarginal gyri (p = 0.002). After multiple comparison correction, only the right supramarginal gyrus was significantly smaller (p = 0.02). When considering only MBI emotional dysregulation, the right parahippocampal and supramarginal gyrus' cortical thicknesses were significantly smaller in this MBI group (p = 0.03, 0.01). However, multiple comparison correction identified no significant differences (p = 0.14, 0.11). Overall MBI and the emotional dysregulation domains were associated with reduced cortical thickness in the right parahippocampal and supramarginal gyri. Since neurodegeneration in the medial temporal and parietal lobe precedes early Alzheimer's disease (AD), MBI, particularly emotion dysregulation, may predict early AD below the diagnostic threshold.

ADHD Symptoms, Peer Problems, and Emotion Dysregulation as Longitudinal and Concurrent Predictors of Adolescent Borderline Personality Features

Objective: ADHD and borderline personality (BP) disorder are highly comorbid and characterized by emotion dysregulation and peer problems. However, limited research has examined social and emotional predictors of BP features in samples that include youth with ADHD. Method: Using a sample of 124 youth with and without ADHD (52% female), ADHD symptoms, peer problems, and emotion dysregulation were assessed in childhood (8–13 years) and in adolescence, along with BP features (13–18 years). Results: In addition to the significant effect of ADHD symptoms, teacher-rated child peer victimization and adolescent-reported peer victimization, poorer close friendships, and emotion dysregulation domains significantly predicted adolescent BP features. Greater parent-rated child and adolescent emotion dysregulation domains also significantly predicted adolescent BP features, with ADHD symptoms no longer significant. Conclusion: Even for youth with ADHD, peer and emotional vulnerabilities in childhood and adolescence may serve as important markers of risk for adolescent BP features.

The Relationship Between Hearing and Mild Behavioral Impairment and the Influence of Sex: A Study of Older Adults Without Dementia from the COMPASS-ND Study.

Background:Hearing loss and mild behavioral impairment (MBI), both non-cognitive markers of dementia, can be early warning signs of incident cognitive decline.Objective:We investigated the relationship between these markers and reported the influence of sex, using non-dementia participants (n = 219; 107 females) from the Canadian Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND).Methods:Hearing was assessed with the 10-item Hearing Handicap for the Elderly–Screening (HHIE-S) questionnaire, a speech-in-noise test, screening audiometry, and hearing aid use. MBI symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Multivariable linear regressions examined the association between hearing and MBI symptom severity and multiple logistic regressions examined the association between hearing and MBI domains.Results:HHIE-S score was significantly associated with greater global MBI symptom burden, and symptoms in the apathy and affective dysregulation domains. Objective measures of audiometric hearing loss and speech-in-noise testing as well as hearing aid use were not associated with global MBI symptom severity or the presence of MBI domain-specific symptoms. Males were older, had more audiometric and speech-in-noise hearing loss, higher rates of hearing-aid use, and showed more MBI symptoms than females, especially apathy.Conclusion:The HHIE-S, a subjective self-report measure that captures emotional and social aspects of hearing disability, was associated with informant-reported global MBI symptom burden, and more specifically the domains of affective dysregulation and apathy. These domains can be potential drivers of depression and social isolation. Hearing and behavior change can be assessed with non-invasive measures, adding value to a comprehensive dementia risk assessment.

Social-Emotional Development and Associated Risk Factors in Chinese Toddlers with Cerebral Palsy.

ObjectiveThis study aimed to analyze the social-emotional behaviors of Chinese toddlers with cerebral palsy and to identify the risk factors associated with these behaviors.MethodsA total of 300 Chinese toddlers and their parents were recruited in this study. A Chinese version of the Infant-Toddler Social-Emotional Assessment was used to assess the children and basic information and clinical data were collected using an author-designed questionnaire. The patients were also assessed using a coping style questionnaire and the hospital anxiety and depression scale. Multiple logistic regression analysis was performed to identify risk factors.ResultsThe scores of the externalizing and competence domains for Chinese toddlers with cerebral palsy at different ages were lower compared to healthy children of the same age and gender (p<0.05). For the boys with cerebral palsy aged between 12–17 and 18–23 months, the scores of the internalizing and dysregulation domains were significantly lower compared to the national normal (p<0.01). The effect of perinatal factors on the externalizing and competence domains was more significant compared to other domains, whilst the coping style of the parents significantly affected the dysregulation domain (p=0.001). Multivariate analysis showed that the parental emotional state, education level, coping style and perinatal factors were closely associated with the social-emotional problems of children with cerebral palsy.ConclusionChildren with cerebral palsy are more likely to have behavioral, emotional, and psychiatric issues that are mostly ignored. These children may benefit from early screening and intervention for risk factors to improve rehabilitation and long-term prognosis.

Posttraumatic stress disorder and deliberate self-harm among military veterans: Indirect effects through negative and positive emotion dysregulation.

Military veterans with posttraumatic stress disorder (PTSD) exhibit heightened rates of deliberate self-harm, yet few studies have explored underlying mechanisms. Addressing this critical gap in the literature, the present study examined the roles of negative and positive emotion dysregulation in the relation between PTSD severity and deliberate self-harm. Data were collected from 465 trauma-exposed military veterans in the community (Mage = 38.00, 71.4% male, 69.5% White) who responded to an online survey. Findings indicated that PTSD severity was indirectly related to deliberate self-harm through overall positive (but not negative) emotion dysregulation. Secondary analyses indicated an underlying role of the negative emotion dysregulation domains of difficulties controlling impulsive behaviors when experiencing negative emotions and lack of emotional clarity and the positive emotion dysregulation domains of nonacceptance of positive emotions, difficulties engaging in goal-directed behavior when experiencing positive emotions, and difficulties controlling impulsive behaviors when experiencing positive emotions in the association between PTSD severity and deliberate self-harm. This study offers preliminary evidence for specific domains of negative and positive emotion dysregulation as possible pathways linking PTSD severity and deliberate self-harm. Findings highlight new avenues for research and treatment focused on the effects of emotion dysregulation on deliberate self-harm among trauma-exposed military veterans. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Transdiagnostic perspective on psychological inflexibility and emotional dysregulation

Psychological inflexibility and emotional dysregulation are a hallmark of psychopathology, being intrinsically embedded in emotional and personality disorders. However, the transdiagnostic mechanisms of psychological inflexibility and emotional dysregulation domains are still a matter of discussion. The present study aims to explore the relationships between cognitive fusion (as a measure of psychological inflexibility), emotion regulation strategies, such as cognitive reappraisal and emotional suppression and emotional dysregulation domains in two different samples. In a cross-sectional design, 297 individuals were assessed with self-report measures and divided into non-clinical (n = 231) and clinical samples (n = 66), according to diagnosis. Results showed that the degree of cognitive fusion was higher in the clinical sample. However, significant correlations between cognitive fusion, emotional regulation strategies and emotional dysregulation domains were found in the two samples. Cognitive reappraisal and emotional dysregulation domains predicted cognitive fusion and mediated the relationship between cognitive fusion and symptomatology in the two samples. Relationships between cognitive fusion and emotional dysregulation domains were found independent of diagnosis. The implementation of emotion regulation strategies may be related to individual differences. However, cognitive fusion, reappraisal and lack of strategies may be core transdiagnostic features in psychological inflexibility and emotion dysregulation.

Gene expression dysregulation domains are not a specific feature of Down syndrome

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), results in a broad range of phenotypes. A recent study reported that DS cells show genome-wide transcriptional changes in which up- or down-regulated genes are clustered in gene expression dysregulation domains (GEDDs). GEDDs were also reported in fibroblasts derived from a DS mouse model duplicated for some Hsa21-orthologous genes, indicating cross-species conservation of this phenomenon. Here we investigate GEDDs using the Dp1Tyb mouse model of DS, which is duplicated for the entire Hsa21-orthologous region of mouse chromosome 16. Our statistical analysis shows that GEDDs are present both in DS cells and in Dp1Tyb mouse fibroblasts and hippocampus. However, we find that GEDDs do not depend on the DS genotype but occur whenever gene expression changes. We conclude that GEDDs are not a specific feature of DS but instead result from the clustering of co-regulated genes, a function of mammalian genome organisation.

Genetics: Up and down in Down's syndrome.

A comparison of identical human twins, only one of whom has Down's syndrome, reveals a genome-wide flattening of gene-expression levels in the affected individual. See Article p.345 Down's syndrome is thought to be caused by gene expression disturbances, so to understand the molecular mechanisms that underlie the phenotype requires an understanding of the transcriptome differences in cells and tissues carrying the total or partial trisomy of chromosome 21 that is typical of the condition. This study of the transcriptome of fetal cells of monozygotic twins discordant for trisomy 21 shows that differential expression between the twins is organized in domains along all chromosomes. These gene expression dysregulation domains are conserved in the mouse model of Down's syndrome and correlate with the lamina-associated domains and replication domains. Although the overall genome topology is not altered in trisomic cells, the authors report modifications of the chromatin environment influencing the overall transcriptome and suggest that the dysregulation domains they identify may therefore contribute to some Down's syndrome phenotypes.

Domains of genome-wide gene expression dysregulation in Down’s syndrome

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.

Are Infant-Toddler Social-Emotional and Behavioral Problems Transient?

To examine the persistence of parent-reported social-emotional and behavioral problems in infants and toddlers. The sample comprised 1,082 children ascertained from birth records. Children were 12 to 40 months old in year 1 (1998-1999) and 23 to 48 months old in year 2 (1999-2000). Eighty percent participated in year 1 and 91% were retained in year 2. Social-emotional and behavioral problems were measured by high scores (> or=90th percentile) on the Internalizing, Externalizing, and/or Dysregulation domains of the Infant-Toddler Social and Emotional Assessment (ITSEA). Parents reported on sociodemographic factors, family life impairment, parenting stress, and family functioning. Among children with any high ITSEA domain score in year 1, 49.9% had persistent psychopathology, as indicated by the continued presence of a high score in year 2. In multivariate analyses, persistence was significantly more likely when parents reported co-occurring problems (i.e., problems in multiple ITSEA domains), high family life disruption, and high parenting distress in year 1. Homotypic persistence rates (i.e., same domain persistence) ranged from 38% to 50%. Only for dysregulation was homotypic persistence greater when co-occurring problems were present than for dysregulation alone. Persistence patterns were similar for boys and girls. Findings indicate that infant-toddler social-emotional/behavioral problems are not transient and highlight the need for early identification, multidomain and family assessment, and effective early intervention.