Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic...

Area of Science:

• Neuroscience
• Genomics
• Molecular Psychiatry

Background:

• The molecular basis of posttraumatic stress disorder (PTSD) is not fully understood due to limited human brain tissue studies.
• Orexigenic neuropeptides (ghrelin, NPY, hypocretin) are linked to negative affect modulation.
• This study leverages the largest functional genomics dataset from human PTSD postmortem brain tissue.

Purpose of the Study:

• Investigate molecular changes in appetitive genes in PTSD.
• Explore the interplay between PTSD and body mass index (BMI) on gene expression.
• Identify potential therapeutic targets for PTSD and associated metabolic conditions.

Main Methods:

• Analyzed transcriptomic data from prefrontal cortex of individuals with and without PTSD.
• Employed gene co-expression network analysis to identify PTSD-specific networks.
• Utilized Ingenuity Pathway Analysis and differential gene expression analysis, stratified by sex and BMI.

Main Results:

• Three PTSD-associated networks involving appetitive gene signaling were identified (2 in females, 1 in all subjects).
• Differential gene expression (DEGs) was observed between PTSD and control groups, particularly in males with elevated BMI.
• Putative upstream regulators, many linked to inflammation, were identified.

Conclusions:

• PTSD-associated transcriptomic modules include appetitive genes, with BMI significantly interacting with PTSD to alter gene expression.
• DEGs and upstream regulators may serve as targets for novel pharmacotherapies.
• This research provides molecular insights into the comorbidity of PTSD and obesity.