Associations among parenting experiences during childhood and adolescence, hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults

Abstract

Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.

Figure 1

Associations between scores of PBI (i.e., care and overprotection) and AUC_net cortisol, or AUC_net ACTH. Blue circles indicate male subjects and green circles indicate female subjects. Spearman's rho correlation, P < 0.05.

Figure 2

Panel (A) shows the brain region including the bilateral hippocampi (blue area), masked by automated anatomical labeling (AAL) of the Wake Forest University (WFU) Pickatlas, which provided an atlas‐based method of generating ROIs. Panel (B) shows the brain region that significantly positively correlated with AUC_net cortisol, as determined by ROI analysis focusing on the hippocampus. The blue lines indicate the left tail in the hippocampus. The statistical threshold was set at P < 0.05 corrected for multiple comparisons at the cluster level and a familywise error rate of P < 0.05 at the voxel level (FWER‐corrected P < 0.05) with adjustments for age, gender, and total GM volume. Panel (C) shows the association between AUC_net cortisol and total hippocampal GM volume, as determined by the mean signal intensities on T1‐weighted images within the bilateral hippocampi. Blue circles indicate male subjects and green circles indicate female subjects. Spearman's rho correlation, P < 0.05.