Identification of rare copy number variants in high burden schizophrenia families

Over the last years, genome‐wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the “common disease, rare variant” hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome‐wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non‐symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc.     

Unconscious thought reduces intrusion development: A replication and extension

Background and ObjectivesIntrusive images after a traumatic event, a hallmark feature of post-traumatic stress disorder, are suggested to develop because the trauma memory is disorganized and not integrated into autobiographical memory. Unconscious Thought Theory predicts that information can be conceptually organized after a period of unconscious thought (UT), more so than after conscious thought (CT). We aimed to test the hypothesis that UT decreases intrusions and increases conceptual organization in memory.MethodsParticipants were shown a stressful film and were required to perform an UT task, a CT task, or a distraction task. Intrusions of the film, intrusion qualities, and sequence memory were measured afterwards.ResultsWe confirmed our hypothesis that UT (versus CT or mere distraction) leads to fewer intrusions, thereby replicating earlier research. Contrary to prediction, we found no difference between the conditions on sequence memory. In addition, conscious thought appeared to increase intrusion nowness and arousal.LimitationsThe analogue design and healthy participant sample prevent from generalizing results to other populations. Intrusion frequency and qualities were assessed immediately after the film thereby prohibiting us from drawing conclusions about any long-term effects.ConclusionsEngaging in unconscious thought after a stressful film can reduce intrusion frequency. This has potential implications for clinical interventions to prevent initial stress symptoms. The underlying mechanism remains unclear for now and provides an avenue for future research.     

The maintenance gap: a new theoretical perspective on the evolution of aging

One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, 'maintenance requirement' has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation. Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms. This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this.     

Lack of long‐term clinical benefit of thrombus aspiration during primary percutaneous coronary intervention with paclitaxel‐eluting stents or bare‐metal stents: Post‐hoc analysis of the PASSION‐trial

Background : Although current clinical guidelines recommend the use of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI), previous studies evaluating TA demonstrated contradictory results. The aim of this study was to evaluate long‐term clinical outcome after TA in adjunct to PPCI for acute ST‐segment myocardial infarction (STEMI), as compared with conventional treatment, with the use of paclitaxel‐eluting stents or bare‐metal stents. Methods : We analyzed data of the PASSION trial, in which 619 patients with STEMI were randomly assigned to a paclitaxel‐eluting stent or a bare‐metal stent. TA was performed in 311 patients (50.2%). Clinical endpoints at 2 years were compared between patients who received TA during PPCI with patients who underwent conventional PPCI. The primary outcome of interest was a composite of cardiac death, recurrent myocardial infarction (MI), or target‐lesion revascularization (TLR). A propensity score model was made to account for baseline differences that could have affected the probability of performing TA. Results : Complete follow‐up was available for 598 patients (96.6%). The cumulative incidence of the combined outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62–1.47; P = 0.84). Also after adjusting for propensity score, no significant difference in event rate was observed between both treatment groups. Conclusions : In this post‐hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of major adverse cardiac events at 2 years follow‐up, as compared with conventional PPCI. © 2011 Wiley Periodicals, Inc.