Prenatal Maternal Depression and the Neurodevelopment of Social Cognition. Open Access

Anderson, Amy (2013)

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Depression during pregnancy is prevalent, under-diagnosed, and under-treated. Children of mothers with major depressive disorder (MDD) during pregnancy often exhibit cognitive, social, emotional, and behavioral dysfunction that persists into adolescence and adulthood. Knowledge of how prenatal depression affects children's brain development is necessary to inform practice guidelines for treating depression during pregnancy.

Twenty one mother-child dyads with longitudinally characterized prenatal and postnatal maternal MDD were studied. The children were behaviorally evaluated and scanned (3T fMRI) at 4-6 years of age. During scanning, they completed a social joint attention task that included affective, cognitive conflict, and attentional demands. Independent Component Analysis (ICA) of fMRI data was conducted to assess the impact of prenatal maternal depression (PMD) on both intrinsic and extrinsic connectivity of three select neural processing networks (the left occipital temporal, limbic, and fronto-cingulate networks).

PMD severity was associated with diminished intrinsic activity within the fronto-cingulate and limbic networks during social conflict trials and was not associated with changes intrinsic activity in the left occipital temporal network. Moreover, PMD was related to increased extrinsic connectivity of the left dorsal lateral prefrontal cortex into the limbic network, decreased extrinsic connectivity of the right inferior frontal gyrus into the limbic network, and decreased extrinsic connectivity of the right anterior cingulate into the fronto-cingulate network. PMD was not related to extrinsic connectivity for the left occipital temporal network.

The present study adds to the limited literature in this subject area by characterizing younger children at risk for mood disorders. Results indicate that exposure to PMD leads to disrupted neural development in the intrinsic and extrinsic functional organization of neural networks. The significance of this outcome is relevant to clinical decision-making related to the aggressive management of moderate to severe depression in pregnancy. This study highlights the neurodevelopmental cost to the offspring of unresolved maternal depression and suggests a re-evaluation of the clinical decision to avoid first-line treatment in pregnancy.

Table of Contents


Chapter 1: Introduction


1.1 Depression during Pregnancy 1

1.1.1 Prevalence and Conventional Wisdom

1.1.2 Treatment Options

1.1.3 Medications on the Fetus

1.1.4 Prenatal Maternal Depression

1.1.5 Animals of Prenatal Depression

1.1.6 Long Term Effects of Prenatal Maternal Depression

1.2 Development of Social Cognition 4

2.1 Joint Attention

1.2.2 Joint Attention and Social Cognition

1.2.3 Social Cognition Neural Circuitry

1.3 Depression 7

1.3.1 Neural Circuitry in Adult Major Depression

1.3.2 Symptoms of Pediatric Depression

1.3.3 Neural Circuitry in Pediatric Depression

1.4 Network Development 10

1.4.1 Neural Maturation in Children

1.4.2 Networks in Adults Facial Perception Limbic System Cognitive Control

Chapter 2: Methods

2.1 Subjects 14

2.1.1 Subject Identification

2.1.2 Subject Inclusion/Exclusion

2.1.3 Calculating Prenatal Depression Burden

2.1.4 Medications

2.2 Behavioral Methods 16

2.2.1 Purpose of Behavioral Assessments

2.2.2 Parent Interview (K-SADS/PAPA)

2.2.3 Child Assessments Play Assessment (ADOS) Intelligence Assessment (WPPSI-III)

2.2.4 Written Assessments Child Behavioral Checklist Social Responsiveness Scale

2.3 Imaging Methods 23

2.3.1 fMRI

2.3.2 Imaging Children Familiarization Phase Scanning Phase

2.3.3 fMRI Methods of this Study fMRI parameters fMRI Tasks for Children Development of Joint Attention Task Task Contrasts Emotion Perception Social Signaling Cognitive Conflict

2.4 Data Analysis 34

2.4.1 Preprocessing

2.4.2 Independent Component Analysis Motion Reduction using ICA

2.4.3 Group Independent Component Analysis Network Identification using ICA Extrinsic Network Analysis Intrinsic Network Analysis Statistical Corrections

2.5 Expected outcomes 29

Tables and Figures

Chapter 3: Results

3.1 Subjects 43

3.1.1 Maternal Variables

3.1.2 Medication Exposure

3.2 Behavioral Results 44

3.2.1 Joint Attention Task results

3.2.2 Behavioral Assessments Child Behavior Checklist (CBCL) Results Social Responsiveness Scale (SRS) Results Other Behavioral Measures

3.3 Group ICA Results 46

3.3.1 Networks Identified

3.3.2 Intrinsic Network Connectivity Occipital-Temporal Network Limbic Network Fronto-Cingulate Network

3.3.3 Extrinsic Network Connectivity Network Network Network

Tables and Figures

Chapter 4: Discussion


4.1 Occipital-Temporal Network 65

4.1.1 Maturity

4.1.2 Intrinsic Connectivity

4.1.3 Extrinsic Connectivity

4.2 Limbic Network 66

4.2.1 Maturity

4.2.2 Intrinsic Connectivity

4.2.3 Extrinsic Connectivity

4.3 Fronto-Cingulate Network 70

4.3.1 Maturity

4.3.2 Intrinsic Connectivity

4.3.3 Extrinsic Connectivity

4.4 Overview of Results 72

4.4.1 Limitations

4.5 Concluding Remarks 74

4.5.1 Implications

Tables and Figures

Supplementary Figures 79

Works Cited 88

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