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Unraveling the Consequences of Childhood Maltreatment: Deviations From Typical Functional Neurodevelopment Mediate the Relationship Between Maltreatment History and Depressive Symptoms

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Abstract

Background

Childhood maltreatment is associated with lifelong psychiatric sequelae. However, our understanding of neurobiological mechanisms responsible for this association is limited. Childhood maltreatment may confer risk for psychopathology by altering neurodevelopmental trajectories during childhood and adolescence. Longitudinal research, which is essential for examining this question, has been limited.

Methods

We investigated maltreatment-associated alterations in the development of neural circuitry. Associations between cumulative childhood maltreatment (assessed using a dimensional measure of abuse and neglect via the Childhood Trauma Questionnaire) and the longitudinal development of resting-state functional connectivity (rsFC) were examined in 130 community-residing adolescents. Functional magnetic resonance imaging data were acquired at age 16 (T1; mean ± SD age, 16.46 ± 0.52 years; 66 females) and age 19 (T2; mean follow-up period, 2.35 years; n = 90 with functional magnetic resonance imaging data at both time points).

Results

We found maltreatment to be associated with widespread longitudinal increases in rsFC, primarily between default mode, dorsal attention, and frontoparietal systems. We also found sex-dependent increased maltreatment-associated rsFC in male participants in salience and limbic circuits. Cross-sectional analyses revealed a shift in maltreatment-related rsFC alterations, which were localized to subcortical and sensory circuits at T1 and to frontal circuits at T2. Finally, longitudinal increases in rsFC connectivity mediated the relationship between childhood maltreatment and increased depressive symptoms.

Conclusions

To our knowledge, this is the first study to examine longitudinal maltreatment-related alterations in rsFC in adolescents. Our findings shed light on the neurodevelopmental consequences of childhood maltreatment and provide evidence for their role in risk for depression.

Section snippets

Participants

Participants were from a large longitudinal study, the OADS (Orygen Adolescent Development Study) [see Whittle et al. (40) for a detailed description]. Briefly, OADS is a longitudinal study that aims to investigate risk and resilience factors for adolescent mental health. Informed consent was obtained from all participants and their parent or guardian at each study wave in accordance with the Human Research Ethics Committee of the University of Melbourne, Australia. Participants underwent

Demographic Information

Demographic information is shown in Table 1 (see Figure S1 for histograms).

Development Is Associated With Widespread Changes in Whole-Brain rsFC

We found longitudinal increases in connectivity across 341 connections and 114 regions (p < .001) (Figure 1A). These were primarily within-network changes: SN (12% of total significant connections), SMN (8%), DMN (5%), and VN (8%). Increases in connectivity were found between some networks, including SN-SMN (18%), DAN-SN (14%), and DAN-LN (5%) (Figure 1B, C). From age 16 to age 19, we found decreases in connectivity

Discussion

The aim of the present study was to examine associations between childhood maltreatment and longitudinal and cross-sectional alterations in rsFC during adolescence. We report that maltreatment was associated with increases in FC primarily between corticocortical circuits from mid adolescence to late adolescence. We also report male-specific associations between maltreatment and increases in rsFC in several connections. Cross-sectionally, we found maltreatment-related increases in FC in

Acknowledgments and Disclosures

This work was supported by the Colonial Foundation, National Health and Medical Research Council (NHMRC) (Program Grant No. 350241, Senior Research Fellowship Grant No. 1136649 [to AZ], and Career Development Fellowship Grant No. 1125504 [to SW]), Australian Research Council (Discovery Grant Nos. DP0878136 and DP1092637), University of Melbourne Research Scholarship (to DR), and Trinity College Dublin Pathfinder Award (to CK).

The authors report no biomedical financial interests or potential

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