Comprehensive analysis of cytokines in depression: independent data from patient plasma and post-mortem ventromedial...

Preclinical and clinical evidence has implicated inflammation in the pathophysiology of depression. Abnormal cytokine levels in blood, cerebrospinal fluid, and post-mortem brain samples have been associated with depression. To our knowledge, however, a comprehensive analysis of cytokine protein levels in brain samples from patients with depression has yet to be conducted in major components of the limbic system such as the ventromedial prefrontal cortex (vmPFC). This region plays a crucial role in depression, impacting cognitive control, emotional regulation, and executive functions. In the current exploratory study, we performed a comprehensive profiling of 72 cytokines, chemokines and growth factors in well-characterized vmPFC samples from 34 depressed suicides and 14 matched sudden-death controls. A human antibody array (RayBio®, chemiluminescent detection) was used to measure all markers. In depressed suicide samples, no significant increase in any cytokine, chemokine or growth factor was detected compared to controls. In comparison, in an independent cohort we measured the levels of 43 inflammatory markers in plasma samples from 141 depressed living subjects and 36 controls using the Mesoscale Discovery V-plex assay. Our analyses indicated no significant difference in the levels of pro- or anti-inflammatory markers in the plasma of cases vs controls. We also conducted a detailed morphological analysis of Iba1-immunostained microglia in vmPFC gray matter samples from 28 depressed suicides and 13 healthy controls. The distributions of the various morphological phenotypes assessed were similar between groups, suggesting that microglia/macrophages do not display signs of morphological changes in the vmPFC of depressed suicides. Taken together, these complementary experiments do not provide evidence of depression-associated neuroinflammatory changes in the vmPFC, at least in the samples analyzed.