Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status

Area of Science:

• Neuroscience
• Genomics
• Psychiatry

Background:

• Major Depressive Disorder (MDD) is a complex condition with varied appetite presentations, including hyperphagic (increased appetite) and hypophagic (decreased appetite) subtypes.
• These appetite phenotypes are linked to cardiometabolic comorbidities, inflammation, and distinct clinical outcomes, but their biological underpinnings are not fully understood.
• Hyperphagia in MDD is associated with atypical depression, reduced stress hormone signaling, inflammation, hypersomnia, and poorer prognosis.

Purpose of the Study:

• To explore peripheral blood RNA expression differences between hyperphagic and hypophagic MDD.
• To investigate the impact of acute stress on these transcriptomic profiles.
• To identify potential peripheral RNA-based biomarkers for MDD endophenotypes.

Main Methods:

• Exploratory bulk RNA sequencing of peripheral blood from unmedicated individuals with hyperphagic MDD (n=7) and hypophagic MDD (n=13).
• Utilized the Maastricht Acute Stress Task to assess stress-related transcriptomic changes.
• Applied stringent statistical methods to control for false positives.

Main Results:

• Baseline analysis revealed increased TADA2B expression and enrichment of 72 inflammation-related gene ontology pathways in hyperphagic MDD.
• Following stress exposure, hyperphagic MDD showed upregulation of CCDC196 and downregulation of SPATA33.
• Gene ontology analysis post-stress identified pathways related to ribosomal activity.

Conclusions:

• Hyperphagic and hypophagic MDD exhibit distinct peripheral RNA expression profiles, which are modulated by stress.
• These findings suggest that peripheral blood RNA signatures may serve as biomarkers for distinct MDD endophenotypes.
• While the study is exploratory and requires replication due to sample size, robust methods support the findings.