Effects of early and concurrent parenting and child cortisol reactivity on hippocampal structure and functional connectivity during childhood: A prospective, longitudinal study

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Offspring of depressed mothers are at increased risk for emotional and behavioral disorders and social impairment. One proposed mechanism of risk transmission is through exposure to maladaptive parenting styles, as depressed mothers display higher levels of hostility and lower levels of support than non-depressed mothers. Rodent models indicate that the early parenting environment programs the endogenous stress response system, the hypothalamic-pituitary-adrenal (HPA) axis, through a cascade of epigenetic processes, ultimately elevating levels of glucocorticoid stress hormones (i.e., cortisol in humans). Elevated cortisol levels have been linked to both structural and functional changes in the hippocampus, a medial temporal lobe structure implicated in regulation of the HPA axis and the pathophysiology of depressive disorders. Despite elucidation of the pathways through which parenting influences neurobiological development in rodents, research examining these associations in humans is only emerging. The present study aimed to translate the rodent literature by examining the effects of early and concurrent parenting on hippocampal structure and functional connectivity during childhood, with a specific emphasis on exploring the mediating role of cortisol reactivity, in a longitudinal sample of offspring of depressed mothers and a community comparison group. At 3-6 and 5-10 years, observational measures of parenting and children’s salivary cortisol responses to a laboratory stressor were assessed. At 5-10 years, children completed structural and resting-state functional MRI scans. Findings revealed timing- and region-dependent associations. Early positive parenting predicted larger hippocampal head volumes whereas concurrent positive parenting predicted smaller body volumes. Early cortisol reactivity predicted larger body volumes whereas concurrent cortisol reactivity predicted smaller tail volumes. Concurrent parenting (positive and negative) predicted hippocampus subregion connectivity with regions of the cerebellum. Early cortisol reactivity predicted increased hippocampal connectivity with the cuneus and regions of the cingulate gyrus. There was a significant indirect effect of greater T1 Negative Parenting on smaller left hippocampal tail volume through increased concurrent cortisol reactivity. Significant interactions with maternal depression were also observed. This research provides a necessary translation of the rodent literature and elucidates possible timing-dependent neurobiological pathways through which early experience may confer increased risk for poor outcomes in human offspring.