Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum

TLDR

Childhood maltreatment is a major risk factor for psychiatric disorders and is linked to reduced adult hippocampal volume, especially on the left, with stress suppressing dentate gyrus neurogenesis and remodeling CA3 dendrites. The study tested whether maltreatment is associated with reduced volumes in hippocampal subfields DG and CA3 using 3‑T MRI and automated FreeSurfer segmentation. A community sample of 193 unmedicated right‑handed adults (38 % male, mean age 21.9 y) was assessed, with maltreatment quantified by the Adverse Childhood Experiences study and Childhood Trauma Questionnaire. Maltreatment correlated most strongly with 6.3 % and 6.1 % volume reductions in left CA2‑CA3 and CA4‑DG, effects not mediated by depression or PTSD, and also produced 4.2 % and 4.3 % reductions in left presubiculum and subiculum, supporting the hypothesis that early stress impairs hippocampal subfield development.

Abstract

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.