Relationships between self-reported childhood traumatic experiences, attachment style, neuroticism and features of borderline personality disorders in patients with mood disorders

Background: Co-occurring borderline personality disorder (BPD) features have a marked impact on treatment of patients with mood disorders. Overall, high neuroticism, childhood traumatic experiences (TEs) and insecure attachment are plausible aetiological factors for BPD. However, their relationship with BPD features specifically among patients with mood disorders remains unclear. We investigated these relationships among unipolar and bipolar mood disorder patients. Methods: As part of the Helsinki University Psychiatric Consortium study, the McLean Screening Instrument (MSI), the Experiences in Close Relationships-Revised (ECR-R), the Short Five (S5) and the Trauma and Distress Scale (TADS) were filled in by patients with mood disorders (n=282) in psychiatric care. Correlation coefficients between total scores of scales and their dimensions were estimated, and multivariate regression (MRA) and mediation analyses were conducted. Results: Spearman's correlations were strong (rho=0.58; p <0.001) between total scores of MSI and S5 Neuroticism and moderate (rho=0.42; p <0.001) between MSI and TADS as well as between MSI and ECR-R Attachment Anxiety. In MRA, young age, S5 Neuroticism and TADS predicted scores of MSI (p <0.001). ECR-R Attachment Anxiety mediated 33% (CI=17-53%) of the relationships between TADS and MSI. Limitations: Cross-sectional questionnaire study. Conclusions: We found moderately strong correlations between self-reported BPD features and concurrent high neuroticism, reported childhood traumatic experiences and Attachment Anxiety also among patients with mood disorders. Independent predictors for BPD features include young age, frequency of childhood traumatic experiences and high neuroticism. Insecure attachment may partially mediate the relationship between childhood traumatic experiences and borderline features among mood disorder patients.Peer reviewe

Differences and similarities of risk factors for suicidal ideation and attempts among patients with depressive or bipolar disorders

Background: Substantial literature exists on risk factors for suicidal behaviour. However, their comparative strength, independence and specificity for either suicidal ideation or suicide attempt(s) remain unclear. Methods: The Helsinki University Psychiatric Consortium (HUPC) Study surveyed 287 psychiatric care patients with ICD-10-DCR depressive or bipolar disorders about lifetime suicidal behaviour, developmental history and attachment style, personality and psychological traits, current and lifetime symptom profiles, and life events. Psychiatric records were used to confirm diagnosis and complement information on suicide attempts. Multinomial regression models predicting lifetime suicidal ideation and single or repeated suicide attempts were generated. Results: Overall, 21.6% patients had no lifetime suicidal behaviour, 33.8% had lifetime suicide ideation without attempts, and 17.1% had a single and 27.5% repeated suicide attempts. In univariate analyses, lifetime suicidal behaviour was associated with numerous factors. In multivariate models, suicidal ideation was independently predicted by younger age, severe depressive disorder, bipolar disorder type II/nos, hopelessness, and childhood physical abuse. Repeated suicide attempts were independently predicted by younger age, female sex, severe depressive disorder with or without psychotic symptoms, bipolar disorder type II/nos, alcohol use disorder, borderline personality disorder traits, and childhood physical abuse. Limitations: Cross-sectional and retrospective study design, utilization of clinical diagnoses, and relatively low response rate. Conclusions: Risk factors for suicidal ideation and attempts may diverge both qualitatively and in terms of dose response. When effects of risk factors from multiple domains are concurrently examined, proximal clinical characteristics remain the most robust. All risk factors cluster into the group of repeated attempters. (C) 2015 Elsevier B.V. All rights reserved.Peer reviewe

Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders

Background: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. Methods: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n = 282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. Results: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho = 0.616, P <0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (r(phi) varied between 0.2 and 0.4, P <0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. Conclusions: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping. (C) 2016 Elsevier Masson SAS. All rights reserved.Peer reviewe

DNA methylation reader MECP2:Cell type- and differentiation stage-specific protein distribution

Background: Methyl-CpG binding protein 2 (MECP2) is a protein that specifically binds methylated DNA, thus regulating transcription and chromatin organization. Mutations in the gene have been identified as the principal cause of Rett syndrome, a severe neurological disorder. Although the role of MECP2 has been extensively studied in nervous tissues, still very little is known about its function and cell type specific distribution in other tissues. Results: Using immunostaining on tissue cryosections, we characterized the distribution of MECP2 in 60 cell types of 16 mouse neuronal and non-neuronal tissues. We show that MECP2 is expressed at a very high level in all retinal neurons except rod photoreceptors. The onset of its expression during retina development coincides with massive synapse formation. In contrast to astroglia, retinal microglial cells lack MECP2, similar to microglia in the brain, cerebellum, and spinal cord. MECP2 is also present in almost all non-neural cell types, with the exception of intestinal epithelial cells, erythropoietic cells, and hair matrix keratinocytes. Our study demonstrates the role of MECP2 as a marker of the differentiated state in all studied cells other than oocytes and spermatogenic cells. MECP2-deficient male (Mecp2−/y) mice show no apparent defects in the morphology and development of the retina. The nuclear architecture of retinal neurons is also unaffected as the degree of chromocenter fusion and the distribution of major histone modifications do not differ between Mecp2−/y and Mecp2wt mice. Surprisingly, the absence of MECP2 is not compensated by other methyl-CpG binding proteins. On the contrary, their mRNA levels were downregulated in Mecp2−/y mice. Conclusions: MECP2 is almost universally expressed in all studied cell types with few exceptions, including microglia. MECP2 deficiency does not change the nuclear architecture and epigenetic landscape of retinal cells despite the missing compensatory expression of other methyl-CpG binding proteins. Furthermore, retinal development and morphology are also preserved in Mecp2-null mice. Our study reveals the significance of MECP2 function in cell differentiation and sets the basis for future investigations in this direction

Small chromosomal regions position themselves autonomously according to their chromatin class

The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) genedepleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes

Organisation of the epidermal syncytial mosaic in Diceratocephala boschmai (Temnocephalida: Platyhelminthes)

The epidermis of Diceratocephala boschmai Baer, 1952 (Temnocephalida: Platyhelminthes) was studied using silver-nitrate staining and electron microscopy. The epidermis consists of six syncytia separated by lateral membranes: the frontal, trunk, stalk, adhesive disc syncytia, and a pair of post-tentacular syncytia. Neighbouring syncytia differ in many characters including (1) the presence or absence of locomotory cilia, (2) the degree of the differentiation of the apical cytoplasm layer, (3) the presence or absence of bundles of cytoskeletal filaments, imaginations of basal membrane and other specialised cytoplasmatic structures, (4) the abundance of hemidesmosomes at the basal membrane, and (5) the abundance and nature of gland ducts penetrating the syncytium. These structural differences reflect functional differences between the syncytia. Thus, multisyncytial organisation of the epidermis may be explained by functional differences between the syncytia. Only between the frontal and trunk syncytia has no apparent ultrastructural difference been found

The Overall Anxiety Severity and Impairment Scale as an Outcome Measure in Internet-Delivered Cognitive Behavioral Therapy for Anxiety Disorders: Observational Study

BackgroundInternet-delivered cognitive behavioral therapy (iCBT) is effective in the treatment of anxiety disorders. iCBT clinical trials use relatively long and time-consuming disorder-specific rather than transdiagnostic anxiety measurements. Overall Anxiety Severity and Impairment Scale (OASIS) is a brief self-report scale that could offer a universal, easy-to-use anxiety measurement option in disorder-specific and transdiagnostic iCBT programs. ObjectiveWe aimed to investigate relationships between OASIS and disorder-specific instruments in iCBT. We expected these relationships to be positive. MethodsWe investigated patients in original nationwide iCBT programs for generalized anxiety disorder (GAD), obsessive-compulsive disorder, panic disorder, and social anxiety disorder, which were administered by Helsinki University Hospital, Finland. In each program, anxiety symptoms were measured using both disorder-specific scales (the 7-item Generalized Anxiety Disorder scale, Penn State Worry Questionnaire, revised Obsessive-Compulsive Inventory, Panic Disorder Severity Scale, and Social Phobia Inventory) and by OASIS. A general linear model for repeated measures (mixed models) and interaction analysis were used for investigating the changes and relationships in the mean scores of OASIS and disorder-specific scales from the first session to the last one. ResultsThe main effect of linear mixed models indicated a distinct positive association between OASIS and disorder-specific scale scores. Interaction analysis demonstrated relatively stable associations between OASIS and the revised Obsessive-Compulsive Inventory (F822.9=0.09; 95% CI 0.090-0.277; P=.32), and OASIS and the Panic Disorder Severity Scale (F596.6=–0.02; 95% CI –0.108 to –0.065; P=.63) from first the session to the last one, while the 7-item Generalized Anxiety Disorder scale (F4345.8=–0.06; 95% CI –0.109 to –0.017; P=.007), Penn State Worry Questionnaire (F4270.8=–0.52; 95% CI –0.620 to –0.437; P<.001), and Social Phobia Inventory (F862.1=–0.39; 95% CI –0.596 to –0.187; P<.001) interrelated with OASIS more strongly at the last session than at the first one. ConclusionsOASIS demonstrates clear and relatively stable associations with disorder-specific symptom measures. Thus, OASIS might serve as an outcome measurement instrument for disorder-specific and plausibly transdiagnostic iCBT programs for anxiety disorders in regular clinical practice

DNA methylation reader MECP2: cell type- and differentiation stage-specific protein distribution.

BACKGROUND Methyl-CpG binding protein 2 (MECP2) is a protein that specifically binds methylated DNA, thus regulating transcription and chromatin organization. Mutations in the gene have been identified as the principal cause of Rett syndrome, a severe neurological disorder. Although the role of MECP2 has been extensively studied in nervous tissues, still very little is known about its function and cell type specific distribution in other tissues. RESULTS Using immunostaining on tissue cryosections, we characterized the distribution of MECP2 in 60 cell types of 16 mouse neuronal and non-neuronal tissues. We show that MECP2 is expressed at a very high level in all retinal neurons except rod photoreceptors. The onset of its expression during retina development coincides with massive synapse formation. In contrast to astroglia, retinal microglial cells lack MECP2, similar to microglia in the brain, cerebellum, and spinal cord. MECP2 is also present in almost all non-neural cell types, with the exception of intestinal epithelial cells, erythropoietic cells, and hair matrix keratinocytes. Our study demonstrates the role of MECP2 as a marker of the differentiated state in all studied cells other than oocytes and spermatogenic cells. MECP2-deficient male (Mecp2 (-/y) ) mice show no apparent defects in the morphology and development of the retina. The nuclear architecture of retinal neurons is also unaffected as the degree of chromocenter fusion and the distribution of major histone modifications do not differ between Mecp2 (-/y) and Mecp2 (wt) mice. Surprisingly, the absence of MECP2 is not compensated by other methyl-CpG binding proteins. On the contrary, their mRNA levels were downregulated in Mecp2 (-/y) mice. CONCLUSIONS MECP2 is almost universally expressed in all studied cell types with few exceptions, including microglia. MECP2 deficiency does not change the nuclear architecture and epigenetic landscape of retinal cells despite the missing compensatory expression of other methyl-CpG binding proteins. Furthermore, retinal development and morphology are also preserved in Mecp2-null mice. Our study reveals the significance of MECP2 function in cell differentiation and sets the basis for future investigations in this direction

Heterochromatin drives compartmentalization of inverted and conventional nuclei

The nucleus of mammalian cells displays a distinct spatial segregation of active euchromatic and inactive heterochromatic regions of the genome(1,2). In conventional nuclei, microscopy shows that euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery(1,2). Genome-wide chromosome conformation capture (Hi-C) analyses show this segregation as a plaid pattern of contact enrichment within euchromatin and heterochromatin compartments(3), and depletion between them. Many mechanisms for the formation of compartments have been proposed, such as attraction of heterochromatin to the nuclear lamina(2,4), preferential attraction of similar chromatin to each other(1,4-12), higher levels of chromatin mobility in active chromatin(13-15) and transcription-related clustering of euchromatin(16,17). However, these hypotheses have remained inconclusive, owing to the difficulty of disentangling intra-chromatin and chromatin-lamina interactions in conventional nuclei(18). The marked reorganization of interphase chromosomes in the inverted nuclei of rods in nocturnal mammals(19,20) provides an opportunity to elucidate the mechanisms that underlie spatial compartmentalization. Here we combine Hi-C analysis of inverted rod nuclei with microscopy and polymer simulations. We find that attractions between heterochromatic regions are crucial for establishing both compartmentalization and the concentric shells of pericentromeric heterochromatin, facultative heterochromatin and euchromatin in the inverted nucleus. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. In addition, our models allow us to rule out mechanisms of compartmentalization that involve strong euchromatin interactions. Together, our experiments and modelling suggest that attractions between heterochromatic regions are essential for the phase separation of the active and inactive genome in inverted and conventional nuclei, whereas interactions of the chromatin with the lamina are necessary to build the conventional architecture from these segregated phases