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Early Neurodevelopment, Adult Human Cognition and Depressive Psychopathology

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Early Neurodevelopment, Adult Human Cognition and Depressive Psychopathology Early Neurodevelopment, adult human cognition and depressive psycho pa thology: analysis of neuroimaging brain correlates and epigenetic mediators Aldo Có rdova Palomera ADVERTIMENT . La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX ( www.tdx.cat ) i a través del Dipòsit Digital de la UB ( diposit.ub.edu ) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’invest igació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB . No s’autoritza la presentació del seu contingut en una finestra o marc a liè a TDX o al Dipòsit Digital de la UB (framing). 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Early neurodevelopment, adult human cognition and depressive psychopathology: analysis of neuroimaging brain correlates and epigenetic mediators Ph.D. thesis presented by Aldo Córdova Palomera Directed by Prof. Dr. Lourdes Fañanás Saura Associate Professor, University of Barcelona Doctoral program in Biomedicine Anthropology Unit – Department of Animal Biology – Faculty of Biology University of Barcelona Lourdes Fañanás Saura Aldo Córdova Palomera Advisor Ph.D. Candidate 1 2 The following funding sources have partly sponsored this doctoral thesis: Ministerio de Educación y Ciencia. Project: “Analysis of epigenetic mechanisms and DNA polymorphisms in candidate genes for schizophrenia and major affective disorders: an approach based on European MZ Twin samples and case-control family designs” (SAF2008-05674-C03-00). ERA-NET NEURON (Network of European Funding for Neuroscience Research). Project: “Genetic factors, brain dysfunction and clinical phenotypes in schizophrenia and autistic disorders” (PIM2010ERN-00642). Centro de Investigación Biomedica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Gobierno de España. The Institute of Biomedicine of the University of Barcelona (IBUB). Generalitat de Catalunya. Sponsorship to the research group "Genes and environment in the comprehension of diversity of human behaviour and the ethiopathogeny of mental illness" (2009SGR827 and 2014SGR1636). National Council for Science and Technology (CONACyT, Mexico). Ph.D. fellowship grant. Part of this thesis was developed at the Dutch Connectome Lab, in the Brain Center Rudolf Magnus (University Medical Center Utrecht). This research stay was conducted under the supervision of Dr. Martijn van den Heuvel, and sponsored by the National Council for Science and Technology (CONACyT, Mexico) and ERA-NET NEURON (Network of European Funding for Neuroscience Research). 3 4 שבקתני למא אלהי אלהי Matthew 27:46 5 6 CONTENTS 1. Introduction ………………………………………………………………………………………. 11 1.1. Neurophysiological plasticity and (ab)normal psychology ……………………………… 13 1.1.1. Phenotypic plasticity in response to the experience ………………………………………… 14 1.1.2. Developmental plasticity: the brain and the early origins of mental disorders …………….. 17 1.1.3. Is there also room for activational plasticity in psychopathology? ………………………… 20 1.2. An empirical approach to psychopathology and plasticity: genetically informative designs ……………………………………………………………………………………………. 21 1.2.1. Gene × Environment interactions ……………………………………………………………… 21 1.2.2. Monozygotic twin designs: classical approaches …………………………………………….. 26 1.2.3. Monozygotic twin designs: epigenetic perspectives ………………………………………… 30 1.2.4. Imaging (epi)genetics ……………………………………………………………………………. 35 1.3. Neural plasticity in depression-related phenotypes: evidences and perspectives …... 40 1.3.1. Developmental plasticity in depression-related phenotypes: early neurodevelopment and risk for adult depression ………………………………………………………………………………… 41 1.3.2. Activational plasticity in depression-related phenotypes: emotional and cognitive flexibility disturbance in depression …………………………………………………………………… 43 1.3.3. Developmental plasticity and depression: additional research hypotheses ……………….. 45 1.3.4. Activational plasticity and depression: additional research hypotheses …………………… 49 2. Hypotheses and objectives ……………………………………………………………………. 51 3. Advisor’s report on the articles ………………………………………………………………. 57 4. Results - Publications ………………………………………………………………………….. 63 4.1. Low birth weight and adult depression: eliciting their association Psychological Medicine (2014), 44, 1117-1119 ……………………………………………………… 65 7 4.2. Birth weight and adult IQ, but not anxious-depressive psychopathology, are associated with cortical surface area: further evidences based on a twin study PLoS ONE (2015) 10(6), e0129616 …………………………………………………………………... 73 4.3. Birth weight, working memory and epigenetic signatures in IGF2 and related genes: a MZ twin study PLoS ONE (2014), 9(8), e103639 …………………………………………………………………….. 91 4.4. Season of birth and subclinical psychosis: systematic review and meta-analysis of new and existing data Psychiatry Research (2015), 225(3), 227-235 ……………………………………………………….. 105 4.5. Cortical thickness correlates of psychotic experiences: examining the effect of season of birth using a genetically informative design Journal of Psychiatric Research (2014), 56, 144-149 ………………………………………………. 119 4.6. Polymorphic variation in the epigenetic gene DNMT3B modulates the environmental impact on cognitive ability: a twin study European Psychiatry (2015), 30(2), 303-308 ………………………………………………………… 129 4.7. Further evidence of DEPDC7 DNA hypomethylation in depression: a study in adult twins European Psychiatry (2015), In press ………………………………………………………………… 139 4.8. Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins Translational Psychiatry (2015), 5, e557 ……………………………………………………………... 147 4.9. Polymorphic variation in FKBP5 interacts with hippocampal connectivity to influence the risk for depression: a study in twins Submitted ………………………………………………………………………………………………… 161 4.10. Altered amygdalar resting-state connectivity in depression is explained by both genes and environment Human Brain Mapping (2015) In press ……………………………………………………………….. 185 5. Global summary of results …………………………………………………………………….. 206 6. Discussion and conclusions ………………………………………………………………….. 211 7. References ……………………………………………………………………………………….. 221 8 9 10 1. INTRODUCTION 11 12 1.1. Neurophysiological plasticity and (ab)normal psychology One of the wide-sense definitions of experience is “an event or occurrence which leaves an impression on someone” (Simpson et al., 1989). In contemporary Psychobiology, it is broadly accepted that human brain organization is fundamentally shaped by experience. This concept would embrace not only factors from outer events, but also “internal” incidents such as genetically encoded developmental changes, or merely psychological processes (Kolb, 1995). In this sense, constantly fluctuating experiential challenges largely influence brain evolution at both phylogenetic and ontogenetic levels (Killackey, 1990). Normally, brain performance and human behavior are characterized by great flexibility in response to these context-specific experiences (Greenough et al., 1987; Gunnar and Nelson, 1992). Biologically, this continuous flow of experiential interactions leading to brain evolution is fostered by brain plasticity, a process consisting of several organized and extremely dynamic steps, which are genetically determined, epigenetically directed and environmentally influenced (Gilbert et al., 2005; Tau and Peterson, 2010). Of note, recent research indicates
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