Elsevier

Biological Psychiatry

Volume 83, Issue 2, 15 January 2018, Pages 128-136
Biological Psychiatry

Archival Report
Amygdala Reward Reactivity Mediates the Association Between Preschool Stress Response and Depression Severity

https://doi.org/10.1016/j.biopsych.2017.08.020Get rights and content

Abstract

Background

Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old.

Methods

Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured.

Results

Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity.

Conclusions

Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression.

Section snippets

Participants

There were 88 preschoolers between 4 and 6 years of age recruited from pediatrician’s offices, daycare centers, and other community resources throughout the greater St. Louis, MO, area. To increase sample variance in depressive symptoms, a validated screening checklist, Preschool Feelings Checklist (PFC) (27), was used to identify preschoolers with and without elevated depressive symptoms. Caregivers indicating that their preschoolers had low (≤1 PFC items endorsed) or high (≥3 PFC items

Demographic and Child Characteristics

See Table 1 for sample demographic and diagnostic characteristics. Average scores were 16.1 (± 6.3; range, 1–47) for PFC-S, 8 (± 9.2; range, 0–34) for BDI-II, and 35.6 ng/mL (± 5.5; range, 27.23–53.52 ng/mL) for AUCg. Preschoolers with a diagnosis of MDD on the Kiddie Schedule for Affective Disorders and Schizophrenia-Early Childhood version had higher PFC-S scores than children who did not: MDD = 28 (± 10), no MDD = 12.5 (± 8.4) (t50 = 5.4, p < .001). Children not providing usable fMRI data

Discussion

The current study used fMRI to examine whether neural reactivity to reward mediates the relationship between cortisol response following a stressor and depression severity in preschool-age children. Our results extend prior reports in older age groups (14) by showing that both higher total cortisol output following a stressor and attenuated neural sensitivity to highly salient outcomes (i.e., gain and loss) are already related to increased depression severity in preschoolers. They also match

Acknowledgments and Disclosures

This work was supported by the National Institute of Mental Health (Grant Nos. K23 MH098176 and R01 MH110488 to MSG) and McDonnell Center for Systems Neuroscience (to MSG). The National Institute of Mental Health and McDonnell Center for Systems Neuroscience had no further role in the design and conduct of the study; collection, management, analysis, and interpretation of data; or preparation, review, and approval of the manuscript.

We thank the children and their families who participated in

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