Network analysis of plasma proteomes in affective disorders

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• The current classification of affective disorders like major depressive disorder (MDD) and bipolar disorder (BD) lacks robust biological validation.
• Plasma proteomic analysis offers a potential avenue to uncover biological underpinnings and limitations in current diagnostic criteria.

Purpose of the Study:

• To investigate plasma proteome profiles in patients with MDD or BD.
• To identify correlations between protein expression patterns and clinical traits, including childhood trauma and eating behaviors.
• To explore the potential of plasma proteins as biomarkers for affective disorders.

Main Methods:

• Quantified plasma proteomes in 299 patients diagnosed with MDD or BD using multiple reaction monitoring.
• Performed weighted correlation network analysis on 420 protein expression levels.
• Correlated protein modules and hub proteins with clinical variables, including the Childhood Trauma Questionnaire and Symptom Checklist-90-Revised.

Main Results:

• Identified six distinct protein modules within the plasma proteome.
• A module including complement components correlated with childhood trauma severity (r = -0.15, p = 0.009).
• Another module with apolipoproteins associated with overeating symptoms (r = 0.16, p = 0.006).
• Immune response and lipid metabolism pathways were significantly enriched in identified modules.
• No protein module significantly differentiated between MDD and BD.

Conclusions:

• Plasma protein networks are significantly associated with childhood trauma and overeating symptoms in patients with affective disorders.
• These clinical features, rather than distinct proteomic signatures, may serve as crucial endophenotypes.
• The findings suggest a need to consider these factors in the biological understanding and potential treatment of MDD and BD.