Relationship between SLC6A2 gene polymorphisms and brain volume in Han Chinese adults who lost their sole child.

BACKGROUND: Norepinephrine transporter (NET) is encoded by the SLC6A2 gene and is a potential target for studying the pathogenesis of PTSD. To the best of our knowledge, no prior investigations have examined SLC6A2 polymorphism-related neuroimaging abnormalities in PTSD patients. METHODS: In 218 Han Chinese adults who had lost their sole child, we investigated the association between the T-182 C SLC6A2 genotype and gray matter volume (GMV). Participants included 57 PTSD sufferers and 161 non-PTSD sufferers, and each group was further separated into three subgroups based on each participant's SLC6A2 genotype (TT, CT, and CC). All participants received magnetic resonance imaging (MRI) and clinical evaluation. To assess the effects of PTSD diagnosis, genotype, and genotype × diagnosis interaction on GMV, 2 × 3 full factorial designs were used. Pearson's correlations were used to examine the association between GMV and CAPS, HAMD, and HAMA. RESULTS: The SLC6A2 genotype showed significant main effects on GMV of the left superior parietal gyrus (SPG) and the bilateral middle cingulate gyrus (MCG). Additionally, impacts of the SLC6A2 genotype-diagnosis interaction were discovered in the left superior frontal gyrus (SFG). The CAPS, HAMA, and HAMD scores, as well as the genotype main effect and diagnostic SLC6A2 interaction, did not significantly correlate with each other. CONCLUSION: These findings indicate a modulatory effect that the SLC6A2 polymorphism exerts on the SPG and MCG, irrespective of PTSD diagnosis. We found evidence to suggest that the SLC6A2 genotype-diagnosis interaction on SFG may potentially contribute to PTSD pathogenesis in adults who lost their sole child.

RORA rs8042149 polymorphism moderates the association between PTSD symptom severity and transverse temporal gyrus thickness in Han Chinese adults who lost their only child.

BACKGROUND: The G allele in retinoid-related orphan receptor alpha (RORA, rs8042149) gene is associated with post-traumatic stress disorder (PTSD) diagnosis and more severe symptoms, reported in the first genome-wide association study of PTSD and subsequent replication studies. Although recent MRI studies identified brain structural deficits in RORA rs8042149 risk G allele carriers, the neural mechanism underlying RORA-related brain structural changes in PTSD remains poorly understood. METHODS: This study included 227 Han Chinese adults who lost their only child. Cortical thickness and subcortical volume were extracted using FreeSurfer, and PTSD severity was assessed using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to assess the interaction effect between RORA genotypes (T/T, G/T, and G/G) and PTSD severity on cortical and subcortical structures. RESULTS: Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness. For individuals with the homozygous T/T genotype, current PTSD symptom severity was positively associated with bilateral transverse temporal gyrus thickness. For individuals with heterozygous G/T genotype, current PTSD symptom severity was negatively associated with the left transverse temporal gyrus thickness. No significant main or interaction effects were found in any subcortical regions. LIMITATION: Cross-sectional design of this study. CONCLUSION: These findings suggest that the non-risk T/T genotype - but not the risk G allele carriers - has a potentially protective or compensatory role on temporal gyrus thickness in adults who lost their only child. These results highlight the moderation effect of RORA polymorphism on the relationship between PTSD symptom severity and cortical structural changes.