Trans-diagnostic, domain- or symptom-focused approaches have been heralded as advancing psychiatric research, but relatively few clinical research programmes have been undertaken to leverage their... Show moreTrans-diagnostic, domain- or symptom-focused approaches have been heralded as advancing psychiatric research, but relatively few clinical research programmes have been undertaken to leverage their potential. In this manuscript we describe the approach and protocol for an exploratory study, PRISM (Psychiatric Ratings using Intermediate Stratified Markers), that will be conducted to explore the biomarkers in schizophrenia (SZ) and Alzheimer's Disease (AD) that may be related to a common symptom, social withdrawal. Patient participants (N = 72 SZ and N = 72 AD study completers), will complete a series of fMRI, EEG, and behavioural paradigms, as well as contributing blood-derived (e.g. epigenetic) and smartphone data related to social behaviour. Self- as well as caregiver- and researcher-reported assessments will be provided to characterise social withdrawal. Normative data will also be collected from a group of healthy controls (N = 48 study completers), half of whom will be matched in terms of age and gender distribution to the SZ and AD group, respectively. Thus we will explore both differentiation and cross-diagnostic overlap in the biomarkers associated with different levels of social withdrawal in SZ and AD. In this way we aim to provide a deeper understanding of the biological underpinnings of symptomatology common to both disorders, and provide insights into novel treatment targets and future drug development approaches. Show less
Jacobs, M.; Zwaan, K.F. van der; Hart, E.P.; Groeneveld, G.J.; Roos, R.A.C. 2019
The distinction between potentiality and actuality in Aristotle has its origin in Platonic ethics. In his psychological and ethical works Aristotle’s notion of potentiality is embedded in a causal... Show moreThe distinction between potentiality and actuality in Aristotle has its origin in Platonic ethics. In his psychological and ethical works Aristotle’s notion of potentiality is embedded in a causal framework that is characteristic of life in general. A key theme is the distinction of various meanings of ‘to know’. In his early work the possession of knowledge is distinguished from its use. In De anima Aristotle adds the potentiality for acquiring knowledge as characteristic of the genus human being. He argues that the stages of actualization of knowledge are instances of a more comprehensive biological and ethical development. Life is the fulfillment of soul as formal, efficient and final cause, with the potentiality of body as material cause. The unity of body and soul is derived from the causal nexus of potentiality and actuality, like a power and the instrument in which it resides. In such cases potentiality is complex and depends on numerous conditions. Failure of full realization may occur when any of the necessary conditions of the development and realization of the fulfillment of human life are lacking, whether in the environment (e.g. climate), the body (illness, drunkenness), or the soul (natural virtue, firm character, attention). Show less
Habets, E.J.J.; Taphoorn, M.J.B.; Klein, M.; Vissers, T.; Dirven, L. 2018
With increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year... Show moreWith increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year-olds when they have multimorbidity, polypharmacy or frailty. Large trials showed that lowering BP in >60-year-olds is beneficial and lowers the risk for myocardial infarction, stroke and all-cause mortality. However, these trials lack generalizability and typically excluded multimorbid patients that are frail. At the same time, observational studies rose concerns about lowering BP too much since there are several cohort studies showing a reverse association of low BP and increased mortality especially in >75-year-olds. The general aim of this thesis is to increase the scientific knowledge about the effects of treating hypertension in >75-year-olds with frailty. This thesis has three aims: 1) to measure the prevalence of polypharmacy in older patients; 2) to test for an association between low SBP and mortality, cognitive function, daily functioning, and QoL in older patients under antihypertensive treatment; and 3) to understand the role that frailty plays in GP decisions about treating hypertension in old age across countries and see if those differences can be explained by country-specific cardiovascular disease burden and life expectancy. Show less
In deze thesis wordt het argument verdedigd dat de manier waarop geometrische patronen als decoraties functioneren precies laat zien hoe representatie werkt. Het argument ontvouwt zich onder... Show moreIn deze thesis wordt het argument verdedigd dat de manier waarop geometrische patronen als decoraties functioneren precies laat zien hoe representatie werkt. Het argument ontvouwt zich onder meer door middel van een uitgebreide analyse van het recente ‘core knowledge’ paradigma uit de cognitieve psychologie. Core knowledge onderzoekers stellen dat culturele fenomenen zoals muziek, taal en visuele patronen, geworteld zijn in aangeboren kennissystemen bijvoorbeeld op het gebied van geometrie en nummer. Hieruit wordt duidelijk dat iedereen over dezelfde mentale bouwstenen beschikt om abstracte patronen te herkennen en te maken. Een analyse van onderzoek uit de antropologie en de semiotiek toont aan dat ook het vermogen om abstracte tekens als representatie van een ander object, lichaam of idee te zien, in elk mens aanwezig moet zijn. Met behulp van theorieën over representatie uit de kunstgeschiedenis, zoals die van Leon Battista Alberti en Gottfried Semper, wordt ten slotte duidelijk hoe het maakproces verloopt door middel waarvan abstracte tekens representaties worden. Geconcludeerd wordt dat als zodanig geometrisch decoratieve patronen op z’n minst en per definitie altijd naar een menselijke maker verwijzen en daarmee naar intentionaliteit. Show less
Zielonka, D.; Ren, M.; Michele, G. de; Roos, R.A.C.; Squitieri, F.; Bentivoglio, A.R.; ... ; Landwehrmeyer, G.B. 2018
Children spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting... Show moreChildren spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting with others. Understanding the emotion processes that underlie successful social functioning is important, especially in children that experience difficulties in social-emotional functioning such as children with Autism Spectrum Disorders (ASD). These studies used a unique approach towards understanding the complex mechanisms that are involved in emotion processing, incorporating how emotions are perceived, experienced, regulated, and expressed. Sensitive and direct measures of emotion processing such as eyetracking and physiology revealed for the first time on a neurobiological level that children with ASD have difficulties emotionally resonating with others, use less efficient strategies to regulate their emotions, and provided evidence for a possible discordance between the expression and experience of emotions. The preschool years also presented with a possible window of opportunity; children with ASD do feel emotions when it comes to their own experiences and the development of social attention towards others might be prone to improvements during the preschool years. These findings are important to parents and professional and enhance the understanding of emotion processing during these very early years of life. Show less
Boer, A. de; Vermeulen, K.; Egger, J.I.M.; Janzing, J.G.E.; Leeuw, N. de; Veenstra-Knol, H.E.; ... ; Kleefstra, T. 2018
This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
This thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or... Show moreThis thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or nicotinic acetylcholine receptors. The thesis reveals part of the complexity of the cholinergic system, its changes related to aging, its relationship with cognitive function and performance, and its role in inflammation. Additionally, the methodology described in the thesis provides controlled circumstances using repeated measurement of drug concentrations and effects during a pharmacologic cholinergic challenge that can be used in drug development of new compounds with cholinergic activity. Show less
