Childhood adversity and adult health:The role of developmental timing and associations with accelerated aging

Childhood adversity has been associated with poor adult health. However, it is unclear whether timing of adversity matters in this association and whether adversity is related to poorer age-related physical health status. A representative sample of the adult Dutch population (N = 3,586, age M = 54.94, age range = 18–92) completed surveys on health and diagnoses of age-related diseases. Information about weight and fat percentage was collected using weighing scales and childhood experiences were assessed retrospectively. Adversity was associated with higher body mass index and fat percentage, more physical problems, and high cholesterol, and this association was most pronounced in individuals with experiences of adversity during early adolescence. In addition, individuals with adversity more often reported physical problems or a medical diagnosis at a younger age. This study indicates that (1) timing of exposure to adversity matters in the relationship between experienced childhood adversity and health and (2) adversity is associated with a higher prevalence of age-related diseases at earlier ages

Situation selection and modification in social inhibition:A person-centered approach

Objectives The current study aimed to identify patterns of situation selection and modification behaviors using a person-centered approach, and to examine to what extent the trait social inhibition (SI) is associated with these patterns of situation-targeted emotion regulation. Methods The sample comprised 504 participants (Mage = 21.5, SD = 8.2; 82% women), who completed questionnaires on situation selection and modification behaviors, and the social inhibition questionnaire (SIQ15). A three-step latent profile analysis (LPA) was performed to (A) identify existing latent profiles of situation avoidance and approach and situation modification behaviors, and (B) to examine the association of SI and facets with the latent class posteriors. Results LPA revealed the presence of four profiles that differed in how situation selection and modification were applied. SI, behavioral inhibition, and social withdrawal were significantly associated with a higher odds of belonging to the profile characterized by avoidance selection and modification. Interpersonal sensitivity was associated with using more conversational modification behaviors, which may illustrate that interpersonal sensitive individuals are motivated to approach, but use avoidance behaviors to prevent confrontation. Conclusions SI individuals particularly rely on avoidance selection and modification behaviors, which may be considered maladaptive emotion regulation

Social inhibition and approach-avoidance tendencies towards facial expressions

This study examined how different manifestations of social inhibition (behavioral inhibition, interpersonal sensitivity, and social withdrawal) are related to automatic approach/avoidance behaviors in a social context. A sample of 115 undergraduate students and 20 adults from the general population (Mage = 24.8, SD = 11.4; 75% women) were assessed with the 15-item Social Inhibition Questionnaire (SIQ15). During a facial expression version of the Approach-Avoidance Task (AAT), participants reacted to images of emotional facial expressions (angry, happy, and neutral) or to control images (neutral objects) in portrait or landscape formats by pulling a joystick towards themselves (approach) or pushing it away from themselves (avoidance). The superordinate social inhibition construct was not associated with approach/avoidance tendencies. However, individuals high in the interpersonal sensitivity domain of social inhibition showed stronger approach tendencies for happy and neutral facial expressions compared to neutral objects, which may relate to their focus on seeking the approval of others

Stability of the pregnancy obsessive compulsive personality disorder symptoms checklist

Because stability over time is central to the definition of personality disorder, aim of the current study was to determine the stability of the Pregnancy Obsessive-Compulsive Personality Disorder (OCPD) Symptoms Checklist (N = 199 women). Strong positive correlations between assessments at 32 weeks of pregnancy and 2 and 3–3.5 years after childbirth were found (r between .62–.72), and the group mean score did not change over time. The Pregnancy OCPD Symptoms Checklist assesses stable, trait-like symptoms of OCPD. Keywords: Obsessive-compulsive personality disorder, Stability, Personality, Validatio

Predicting young children's externalizing problems:Interactions among effortful control, parenting, and child sex

This study investigated interactions between observed temperamental effortful control and observed parenting in the prediction of externalizing problems. Child gender effects on these relations were examined. The relations were examined concurrently when the child was 3 years old and longitudinally at 4.5 years. The sample included 89 two-parent families and their firstborn children. Children with a low level of effortful control were most at risk of displaying externalizing problems. However, more parental positive control seemed to buffer this risk. Boys were at risk of displaying externalizing problems, but again this was buffered by parental positive control. Effortful control was more strongly related to concurrent externalizing problems in boys than in girls, but girls’ effortful control had a greater long-term effect on externalizing problems

Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies

Alpha-synuclein (ASYN) is a major constituent of the typical protein aggregates observed in several neurodegenerative diseases that are collectively referred to as synucleinopathies. A causal involvement of ASYN in the initiation and progression of neurological diseases is suggested by observations indicating that single-point (e.g., A30P, A53T) or multiplication mutations of the gene encoding for ASYN cause early onset forms of Parkinson's disease (PD). The relative regional specificity of ASYN pathology is still a riddle that cannot be simply explained by its expression pattern. Also, transgenic over-expression of ASYN in mice does not recapitulate the typical dopaminergic neuronal death observed in PD. Thus, additional factors must contribute to ASYN-related toxicity. For instance, synucleinopathies are usually associated with inflammation and elevated levels of oxidative stress in affected brain areas. In turn, these conditions favor oxidative modifications of ASYN. Among these modifications, nitration of tyrosine residues, formation of covalent ASYN dimers, as well as methionine sulfoxidations are prominent examples that are observed in post-mortem PD brain sections. Oxidative modifications can affect ASYN aggregation, as well as its binding to biological membranes. This would affect neurotransmitter recycling, mitochondrial function and dynamics (fission/fusion), ASYN's degradation within a cell and, possibly, the transfer of modified ASYN to adjacent cells. Here, we propose a model on how covalent modifications of ASYN link energy stress, altered proteostasis, and oxidative stress, three major pathogenic processes involved in PD progression. Moreover, we hypothesize that ASYN may act physiologically as a catalytically regenerated scavenger of oxidants in healthy cells, thus performing an important protective role prior to the onset of disease or during aging

Distinct mechanisms eliminate mother and daughter centrioles in meiosis of starfish oocytes

Centriole elimination is an essential process that occurs in female meiosis of metazoa to reset centriole number in the zygote at fertilization. How centrioles are eliminated remains poorly understood. Here we visualize the entire elimination process live in starfish oocytes. Using specific fluorescent markers, we demonstrate that the two older, mother centrioles are selectively removed from the oocyte by extrusion into polar bodies. We show that this requires specific positioning of the second meiotic spindle, achieved by dynein-driven transport, and anchorage of the mother centriole to the plasma membrane via mother-specific appendages. In contrast, the single daughter centriole remaining in the egg is eliminated before the first embryonic cleavage. We demonstrate that these distinct elimination mechanisms are necessary because if mother centrioles are artificially retained, they cannot be inactivated, resulting in multipolar zygotic spindles. Thus, our findings reveal a dual mechanism to eliminate centrioles: mothers are physically removed, whereas daughters are eliminated in the cytoplasm, preparing the egg for fertilization.European Molecular Biology Laboratory (EMBL)- EMBL International PhD Program; Laura and Arthur Colwin Endowed Summer Research Fellowship; Deutsche Forschungsgemeinschaft grant: (MU1423/4-1)

Obsessive-compulsive personality disorder symptoms as a risk factor for postpartum depressive symptoms

For women with obsessive-compulsive personality disorder (OCPD) trait symptoms, coping with childbearing and parenting could be associated with postpartum depressive symptoms. Therefore, the possible relationship between OCPD trait symptoms and trajectories of postpartum depressive symptoms was examined. A cohort of 1427 women was followed from late pregnancy until 12 months’ postpartum. Trajectories of postpartum depressive symptoms were determined using growth mixture modeling with five repeated assessments. Next, the relationship between OCPD trait symptoms and these trajectories was examined through multinomial regression. Three postpartum depressive symptom trajectories were identified: (1) low symptoms (92%), (2) increasing-decreasing symptoms (inverted u-shape) (5%), and (3) increasing symptoms (3%). OCPD trait symptoms were associated with a higher likelihood of the trajectories increasing-decreasing symptoms (OR 1.26; 95% CI 1.14–1.39) and increasing symptoms (OR 1.16; 95% CI 1.02–1.32), compared to reference trajectory (low symptoms), adjusted for age, educational level, unplanned pregnancy, previous depressive episode (s), and parity

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a “step down” therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013–004122-28. 24/09/2013