Moderation of Menopause Stage on Childhood Trauma’s Effect on Psychiatric Symptoms and Brain Structure Restricted; Files Only

Abstract

Childhood trauma affects approximately two-thirds of U.S. adults and is associated with long-term psychiatric and neurobiological consequences, with women showing particularly strong associations with internalizing psychopathology. For women, the menopausal transition represents a period of heightened vulnerability due to hormonal fluctuations, yet the interaction between childhood trauma and reproductive aging on mental health and the brain remains poorly understood, particularly in Black and African American women. This longitudinal study examined whether childhood trauma associated with psychiatric symptoms and brain structure changes in Black or African American women during the menopausal transition and whether these relationships are moderated by menopausal stage. Participants completed questionnaires at enrollment and during study visits at baseline, 6 months, and 18 months, where neuroimaging data was also obtained. Reproductive stage was assessed prospectively with weekly menstrual surveys using the Stages of Reproductive Aging Workshop +10 (STRAW+10) staging system, and linear mixed effects models were used to test the study's hypotheses. Psychiatric symptom severity increawsed across menopause. Childhood trauma was positively associated with psychiatric symptoms during premenopause and early postmenopause. Left hippocampal subcortical volume and left frontal pole surface area increases correlated with advancing menopause, contradicting predictions of decreases due to ovarian hormone changes. These findings suggest brain changes and a decrease in childhood trauma's psychiatric impact across menopause. Future research should explore why childhood trauma has the strongest impact during premenopause rather than during hormonal fluctuations of perimenopause. The findings suggest hope of some protection from childhood trauma for women during midlife.

Table of Contents

Introduction………………….………………….………………….………………….…………..1

Methods………………….………………….………………….………………….……………....8

Section 1. Study Enrollment………………….………………….………………….…………….8

Section 2. Childhood Trauma Questionnaire (CTQ)………………….………………….……….8

Section 3. General Anxiety Disorder-7 Scale (GAD-7)………………….……………………….9

Section 4. PTSD Checklist for DSM-5 (PCL-5)………………….………………….……………9

Section 5. Patient Health Questionnaire-9 (PHQ-9)………………….………………………….10

Section 6. Neuroimaging Protocol………………….………………….………………………...10

Section 7. Brain Data Processing………………….………………….………………….………10

Section 8. Menopause Stage Survey and Scale………………….………………….…………...12

Section 9. Data Analysis………………….………………….………………….……………….13

Results………………….………………….………………….………………….………………15

Discussion………………….………………….………………….………………….……….….22

Psychiatric Symptom Increase Across the Menopausal Transition………………….…………..22

Attenuation of Childhood Trauma’s Psychiatric Impact Across Menopause……………………23

Menopause as a Window of Neuroplasticity and Recalibration………………….……………...24

Brain Structural Changes Across the Menopausal Transition………………….…………….….27

Limitations and Future Directions………………….………………….………………….……..29

Conclusion………………….………………….………………….………………….………….30

Supplemental Tables………………….………………….………………….…………………...32

References………………….………………….………………….………………….………..…48

Tables

Table 1. Menopausal transition stages and criteria for the STRAW+10 model………………….13

Table 2. Linear mixed model results for transdiagnostic psychiatric symptom severity………...32

Table 3. Simple slopes results for the effect of childhood trauma on psychiatric symptoms……33

Table 4. Linear mixed model results for cortical thickness…………..………………….………34

Table 5. Linear mixed model results for cortical surface area………………….………………..40

Table 6. Linear mixed model results for subcortical volume………………….…………………46

Figures

Figure 1. Interaction between childhood trauma and menopause stage on depressive symptoms………………….………………….………………….………………….…………...16

Figure 2. Interaction between childhood trauma and menopause stage on anxiety symptoms….17

Figure 3. Interaction between childhood trauma and menopause stage on PTSD symptoms…...19

Figure 4. Left hippocampal subcortical volume across menopausal stages……………………..20

Figure 5. Left frontal pole surface area across menopausal stages………………….…………...21

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Mental Health Psychology, Psychobiology Biology, Neuroscience
Keyword	menopause
Committee Chair / Thesis Advisor	Stevens, Jennifer, Emory University
Committee Members	Eghbalzad, Leyla, Emory University Massa, Megan, Emory University

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