Psychophysiological responses underlying unresolved loss and trauma in the Adult Attachment Interview

Unresolved loss/trauma in the context of the Adult Attachment Interview (AAI) has been theorised to result from dissociative processing of fear-related memories and ideas. To examine the plausibility of this model, this study tested hypothesised associations between unresolved loss/trauma and indicators of autonomic nervous system (ANS) reactivity. First-time pregnant women (N = 235) participated in the AAI while heart rate (interbeat interval; IBI) and indicators of parasympathetic reactivity (respiratory sinus arrhythmia; RSA) and sympathetic reactivity (pre-ejection period; PEP, skin conductance level; SCL) were recorded. Using multilevel modelling, ANS reactivity was examined in relation to topic (loss/trauma versus other questions); discussion of actual loss/trauma; classification of unresolved/disorganised; and unresolved responses during the interview. Responses to loss/trauma questions and discussion of loss were associated with respectively larger and smaller IBIs. There was no moderation by unresolved/disorganised status. Unresolved responses about loss were associated with smaller IBIs. Participants classified as unresolved/disorganised showed decreasing PEP and blunted SCL throughout the whole interview. The findings suggest that unresolved speech about loss co-occurs with physiological arousal, although the inconclusive findings regarding parasympathetic and sympathetic nervous system responses fail to clearly support the role of fear

Narrowing the Transmission Gap: A Synthesis of Three Decades of Research on Intergenerational Transmission of Attachment

wenty years ago, meta-analytic results (k = 19) confirmed the association between caregiver attachment representations and child–caregiver attachment (Van IJzendoorn, 1995). A test of caregiver sensitivity as the mechanism behind this intergenerational transmission showed an intriguing “transmission gap.” Since then, the intergenerational transmission of attachment and the transmission gap have been studied extensively, and now extend to diverse populations from all over the globe. Two decades later, the current review revisited the effect sizes of intergenerational transmission, the heterogeneity of the transmission effects, and the size of the transmission gap. Analyses were carried out with a total of 95 samples (total N = 4,819). All analyses confirmed intergenerational transmission of attachment, with larger effect sizes for secure-autonomous transmission (r = .31) than for unresolved transmission (r = .21), albeit with significantly smaller effect sizes than 2 decades earlier (r = .47 and r = .31, respectively). Effect sizes were moderated by risk status of the sample, biological relatedness of child–caregiver dyads, and age of the children. Multivariate moderator analyses showed that unpublished and more recent studies had smaller effect sizes than published and older studies. Path analyses showed that the transmission could not be fully explained by caregiver sensitivity, with more recent studies narrowing but not bridging the “transmission gap.” Implications for attachment theory as well as future directions for research are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved)

The latent structure of the adult attachment interview: Large sample evidence from the collaboration on attachment transmission synthesis

The Adult Attachment Interview (AAI) is a widely used measure in developmental science that assesses adults’ current states of mind regarding early attachment-related experiences with their primary caregivers. The standard system for coding the AAI recommends classifying individuals categorically as having an autonomous, dismissing, preoccupied, or unresolved attachment state of mind. However, previous factor and taxometric analyses suggest that: (a) adults’ attachment states of mind are captured by two weakly correlated factors reflecting adults’ dismissing and preoccupied states of mind and (b) individual differences on these factors are continuously rather than categorically distributed. The current study revisited these suggestions about the latent structure of AAI scales by leveraging individual participant data from 40 studies (N = 3,218), with a particular focus on the controversial observation from prior factor analytic work that indicators of preoccupied states of mind and indicators of unresolved states of mind about loss and trauma loaded on a common factor. Confirmatory factor analyses indicated that: (a) a 2-factor model with weakly correlated dismissing and preoccupied factors and (b) a 3-factor model that further distinguished unresolved from preoccupied states of mind were both compatible with the data. The preoccupied and unresolved factors in the 3-factor model were highly correlated. Taxometric analyses suggested that individual differences in dismissing, preoccupied, and unresolved states of mind were more consistent with a continuous than a categorical model. The importance of additional tests of predictive validity of the various models is emphasized

Docking of Secretory Vesicles Is Syntaxin Dependent

Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones

The Role of Rab3a in Secretory Vesicle Docking Requires Association/Dissociation of Guanidine Phosphates and Munc18-1

Rab3a is a small GTPase that binds selectively to secretory vesicles and switches between active, GTP-bound and inactive, GDP-bound conformations. In yeast, Rab and SM-genes interact genetically to promote vesicle targeting/fusion. We tested different Rab3a conformations and genetic interactions with the SM-gene munc18-1 on the docking function of Rab3a in mammalian chromaffin cells. We expressed Rab3a mutants locked in the GTP- or GDP-bound form in wild-type and munc18-1 null mutant cells and analyzed secretory vesicle distribution. We confirmed that wild-type Rab3a promotes vesicle docking in wild-type cells. Unexpectedly, both GTP- and GDP-locked Rab3a mutants did not promote docking. Furthermore, wild-type Rab3a did not promote docking in munc18-1 null cells and GTP- and GDP-Rab3a both decreased the amount of docked vesicles. The results show that GTP- and GDP-locked conformations do not support a Munc18-1 dependent role of Rab3a in docking. This suggests that nucleotide cycling is required to support docking and that this action of Rab3a is upstream of Munc18-1

Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta‐analysis

Parents’ attachment representations and child–parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta‐analysis. Analyses on 4,396 parent–child dyads (58 studies, child age 11–96 months) revealed a combined effect size of r = .29. IPD meta‐analyses revealed that effect sizes for the transmission of autonomous‐secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent–child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta‐analysis are discussed

Morphological docking of secretory vesicles

Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis, neurotransmitter-containing vesicles dock to the target membrane. In electron micrographs of neurons and neuroendocrine cells, like chromaffin cells many synaptic vesicles (SVs) and large dense-core vesicles (LDCVs) are docked. For many years the molecular identity of the morphologically docked state was unknown. Recently, we resolved the minimal docking machinery in adrenal medullary chromaffin cells using embryonic mouse model systems together with electron-microscopic analyses and also found that docking is controlled by the sub-membrane filamentous (F-)actin. Currently it is unclear if the same docking machinery operates in synapses. Here, I will review our docking assay that led to the identification of the LDCV docking machinery in chromaffin cells and also discuss whether identical docking proteins are required for SV docking in synapses

A Comparative Computer Simulation of Dendritic Morphology

Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity

Multidimensional prognostic indices for use in COPD patient care. A systematic review

Contains fulltext : 98117.pdf (publisher's version ) (Open Access)BACKGROUND: A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use. Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice. METHODS: We performed a systematic literature search in both Pubmed and Embase up to September 2010. Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only. Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies. RESULTS: Of 7,028 articles screened, 13 studies comprising 15 indices were included. Only 1 index had been explored for its application in daily practice. We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation. Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea. The quality of the studies underlying the indices varied between fairly poor and good. Statistical methods to assess the predictive abilities of the indices were heterogenic. They generally revealed moderate to good discrimination, when measured. Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity. CONCLUSIONS: We identified 15 prognostic COPD indices. Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation. Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this

Structure-Function Study of Mammalian Munc18-1 and C. elegans UNC-18 Implicates Domain 3b in the Regulation of Exocytosis

Munc18-1 is an essential synaptic protein functioning during multiple stages of the exocytotic process including vesicle recruitment, docking and fusion. These functions require a number of distinct syntaxin-dependent interactions; however, Munc18-1 also regulates vesicle fusion via syntaxin-independent interactions with other exocytotic proteins. Although the structural regions of the Munc18-1 protein involved in closed-conformation syntaxin binding have been thoroughly examined, regions of the protein involved in other interactions are poorly characterised. To investigate this we performed a random transposon mutagenesis, identifying domain 3b of Munc18-1 as a functionally important region of the protein. Transposon insertion in an exposed loop within this domain specifically disrupted Mint1 binding despite leaving affinity for closed conformation syntaxin and binding to the SNARE complex unaffected. The insertion mutation significantly reduced total amounts of exocytosis as measured by carbon fiber amperometry in chromaffin cells. Introduction of the equivalent mutation in UNC-18 in Caenorhabditis elegans also reduced neurotransmitter release as assessed by aldicarb sensitivity. Correlation between the two experimental methods for recording changes in the number of exocytotic events was verified using a previously identified gain of function Munc18-1 mutation E466K (increased exocytosis in chromaffin cells and aldicarb hypersensitivity of C. elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding