Influence of genetic polymorphism and trauma on cortical structures and PTSD severity: Imaging genetics generalized...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Posttraumatic stress disorder (PTSD) is linked to brain structure alterations and genetic factors.
• Potentially traumatic events (PTEs) and gene polymorphisms influence PTSD development and severity.

Purpose of the Study:

• To investigate the pathophysiology of PTSD by examining the interplay of PTEs, gene polymorphisms, and brain region volumes.
• To utilize imaging genetics generalized structured component analysis (IG-GSCA) to model these complex relationships.

Main Methods:

• Structural MRI and genotyping for nine genes were performed on 231 participants (including PTSD patients and healthy controls).
• Psychological assessments measured PTEs, PTSD symptoms, and alcohol problems.
• IG-GSCA modeled gene/PTE effects on 60 brain ROI volumes, mediating PTSD severity.

Main Results:

• The HTR3A gene correlated with anterior cingulate gyrus volume; NR3C1 correlated with central operculum volume.
• Volumes of the central operculum, occipital fusiform gyrus, and anterior cingulate gyrus were negatively associated with PTSD severity.
• PTEs were positively associated with PTSD severity.

Conclusions:

• A significant indirect pathway was found from the NR3C1 gene polymorphism to PTSD severity, mediated by central operculum volume.
• The anterior cingulate gyrus and occipital fusiform gyrus volumes showed significant associations with PTSD symptom severity.
• This study provides a comprehensive model integrating genetic, environmental, and neuroanatomical factors in PTSD.