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Intergenerational Transmission of Childhood Maltreatment

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Intergenerational Transmission of Childhood Maltreatment INTERGENERATIONAL TRANSMISSION OF CHILDHOOD MALTREATMENT: CHARACTERIZING POTENTIAL MECHANISMS AND OFFSPRING NEUROBEHAVIORAL OUTCOMES By Mollie Christine Marr A DISSERTATION Presented to the Department of Behavioral Neuroscience and the Oregon Health & Science University School of Medicine In partial fulfillment of the requirements for the degree of Doctor of Philosophy December 17th, 2020 School of Medicine Oregon Health & Science University CERTIFICATE OF APPROVAL _______________________________________ This is to certify that the PhD dissertation of Mollie C. Marr has been approved ________________________________________ Alice Graham, PhD, Mentor/Advisor ________________________________________ Damien Fair PA-C, PhD, Mentor/Advisor ________________________________________ Bonnie Nagel, PhD, Committee Chair ________________________________________ Suzanne Mitchell, PhD, Member ________________________________________ Kristen Mackiewicz Seghete, PhD, Member ________________________________________ Hanna Gustafsson, PhD, Member ii TABLE OF CONTENTS Table of Contents .............................................................................................................. ii Figures Contents .............................................................................................................. vi Table Contents ............................................................................................................... viii Abbreviations .................................................................................................................. xii Acknowledgments ............................................................................................................xv Abstract ......................................................................................................................... xxiii Chapter 1. Introduction ...................................................................................................1 1.1 Childhood Maltreatment .......................................................................................1 1.2 Intergenerational Transmission of Childhood Maltreatment ................................8 1.3 Developmental Programming .............................................................................14 1.4 Early Brain Development ....................................................................................25 1.5 Resting-state Functional Connectivity MRI in Developmental Research ..........33 1.6 Associated Developmental Outcomes .................................................................35 1.7 Goals of the Dissertation .....................................................................................40 Chapter 2. Maternal Perinatal Stress and Offspring Amygdala Connectivity and Negative Affect Development ..........................................................................................46 2.1. Abstract ...............................................................................................................47 2.2. Introduction .........................................................................................................48 2.3. Methods and Materials ........................................................................................50 iii 2.4. Results .................................................................................................................62 2.5. Discussion ...........................................................................................................76 2.6. Conclusions .........................................................................................................83 2.7. Supplemental Materials .......................................................................................84 Chapter 3. Intergenerational Effect of Maternal Exposure to Childhood Maltreatment and Associations with Neonatal Amygdala Functional Connectivity and Infant Biobehavioral Outcomes ............................................................................114 3.1 Abstract .............................................................................................................114 3.2 Introduction .......................................................................................................116 3.3 Methods and Materials ......................................................................................120 3.4 Results ...............................................................................................................132 3.5 Discussion .........................................................................................................137 3.6 Conclusions .......................................................................................................146 3.7 Supplemental Materials .....................................................................................147 Chapter 4. Intergenerational Effect of Maternal Exposure to Childhood Maltreatment and Associations with Neonatal Hippocampal Functional Connectivity ....................................................................................................................155 4.1 Abstract .............................................................................................................155 4.2 Introduction .......................................................................................................157 4.3 Methods and Materials ......................................................................................162 4.4 Results ...............................................................................................................173 iv 4.5 Discussion .........................................................................................................180 Chapter 5. Discussion ...................................................................................................188 5.1 Summary of Findings ........................................................................................188 5.2 Characterizing Maternal Psychological Stress During Pregnancy ....................191 5.3 Maternal History of Exposure to Maltreatment During Childhood and the Functional Organization of the Offspring’s Limbic System........................................195 5.4 Leveraging MRI to Examine Functional Heterogeneity ...................................200 5.5 Additional Consideration ..................................................................................202 5.6 Limitations and Future Work ............................................................................209 5.7 Conclusions .......................................................................................................228 References .......................................................................................................................230 v FIGURES CONTENTS Figure 1.1. Intergenerational transmission of childhood maltreatment. ..........................120 Figure 1.2. HPA axis regulation in pregnancy. ..................................................................20 Figure 1.3. Maternal psychological stress during pregnancy can affect fetal limbic system development. ......................................................................................................................24 Figure 1.4. Neurodevelopment during the prenatal period. ...............................................26 Figure 1.5. Overview of dissertation studies. ....................................................................45 Figure 2.1. Functional Random Forest. .............................................................................59 Figure 2.2. Functional Random Forest identified distinct subgroups related to the magnitude of maternal stress. ............................................................................................63 Figure 2.3. Functional Random Forest identified distinct subgroups. ...............................66 Figure 2.4. Infant negative affect growth has an inverted u-shaped trajectory. .................69 Figure 2.5. Maternal stress correlation-based trajectories are similar between primary and replication cohorts. .............................................................................................................70 Figure 2.6. Maternal perinatal stress trajectory clusters are associated with neonatal infant amygdala connectivity. ......................................................................................................74 Figure 2.7. UCI study cohort diagram. ..............................................................................84 Figure 2.8. Maternal psychological stress mean scores by magnitude clusters across pregnancy. ..........................................................................................................................93 Figure 2.9. Maternal psychological stress mean scores by trajectory clusters across pregnancy. ..........................................................................................................................93 vi Figure 3.1. Infant cortisol reactivity during the Strange Situation Paradigm. .................129 Figure 3.2. Left and right neonatal amygdala functional connectivity. ...........................133 Figure 3.3. Neonatal left amygdala to dorsal anterior cingulate cortex (LA-dACC) mediates between maternal exposure to maltreatment during childhood and mother-infant attachment security. .........................................................................................................136
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