Major depressive disorder comorbid with general anxiety disorder: Associations among neuroticism, adult stress, and the inflammatory index

Accumulating evidence shows that higher neuroticism and adult stress may be potential risk factors for major depressive disorder (MDD) comorbid with generalized anxiety disorder (GAD). Studies have shown that anxious and depressed patients have significantly more neurobiological abnormalities than non-anxious depressed patients. However, the biological mechanism of comorbidity remains unknown. A study of serum markers allows a better understanding of the mechanism. This was a multi-centre, cross-sectional study. A total of 169 MDD patients (42 MDD patients with comorbid GAD and 127 MDD patients without comorbid GAD) were studied to analyse the risk factors for MDD with comorbid GAD. Twenty-four peripheral serum markers were measured. Path analysis was applied to test the association among neuroticism, adult stress, inflammatory markers, and psychopathology. After Bonferroni correction, MDD patients with comorbid GAD had lower levels of CCL2 (P = 0.001) and higher levels of α2M (P < 0.001) and TLR-1 (P = 0.001) than MDD patients without comorbid GAD (adjusted P < 0.002). In the path analyses of the association among adult stress, the inflammatory index, and psychopathology, neuroticism had a direct effect (β = 0.238, P = 0.003) and an indirect effect (β = 0.068, P = 0.004) on MDD and GAD comorbidity through adult stress and the inflammatory index. Our results suggest that MDD with comorbid GAD is associated with higher levels of inflammatory markers, stress factors and personality traits, which may provide some cues for early identification or more tailored and comprehensive treatment for MDD with comorbid GAD.