The DRD2 Taq1A polymorphism moderates the effect of PTSD symptom severity on the left hippocampal CA3 volume: a pilot study

RATIONALE AND OBJECTIVES: The hippocampus, especially the CA1, CA3, and dentate gyrus (DG) subfields, is reported to be associated with post-traumatic stress disorder (PTSD) after trauma. However, neuroimaging studies of the associations between PTSD and hippocampal subfield volumes have failed to yield consistent findings. The aim of this study is to examine whether the dopamine D2 receptor (DRD2) Taq1A polymorphism, which is associated with both hippocampal function and PTSD, moderated the association between PTSD severity and hippocampal CA1, CA3 and DG volumes. METHODS: T1-weighted images were acquired from 142 trauma survivors from the 2008 Wenchuan earthquake using a 3.0-T magnetic resonance imaging system. Hippocampal subfield segmentations were performed with FreeSurfer v6.0. We used the simple moderation model from the PROCESS v3.4 tool for SPSS 23.0 to examine the association between the rs1800497 polymorphism, PTSD severity, and hippocampal CA3 and DG volumes. RESULTS: A significant genotype × PTSD symptom severity interaction was found for the left CA3 volume (ΔF = 5.01, p = 0.008, ΔR(2) = 0.05). Post hoc, exploratory analyses deconstructing the interaction revealed that severe PTSD symptomatology were associated with reduced left CA3 volume among TC heterozygotes (t = − 2.86, p = 0.005). CONCLUSIONS: This study suggests that DRD2 Taq1A polymorphism moderates the association between PTSD symptomatology and left CA3 volume, which promotes an etiological understanding of the hippocampal atrophy at the subfield level. This highlights the complex effect of environmental stress, and provides possible mechanism for the relationship between the dopaminergic system and hippocampal function in PTSD.