Interplay between pro-inflammatory cytokines and growth factors in depressive illnesses

Abstract

The development of depressive disorders had long been attributed to monoamine variations, and pharmacological treatment strategies likewise focused on methods of altering monoamine availability. However, the limited success achieved by treatments that altered these processes spurred the search for alternative mechanisms and treatments. Here we provide a brief overview concerning a possible role for pro-inflammatory cytokines and growth factors in major depression, as well as the possibility of targeting these factors in treating this disorder. The data suggest that focusing on one or another cytokine or growth factor might be counterproductive, especially as these factors may act sequentially or in parallel in affecting depressive disorders. It is also suggested that cytokines and growth factors might be useful biomarkers for individualized treatments of depressive illnesses.

Keywords: BDNF; antidepressant; depression; growth factors; pro-inflammatory cytokines; stressors.

Figure 1

This provides a schematic representation of the potential interactive influence of prenatal, childhood, and/or adulthood events and particular genetic variations in affecting inflammatory and growth factors, ultimately leading to specific depressive illnesses. It is suggested that particular gene polymorphism, including that of the growth factor BDNF, may influence vulnerability versus resilience to the emergence of depression, and that this may be moderated by the presence of adverse childhood experiences. In this regard, gene polymorphisms are not seen as necessarily being related to positive or negative outcomes, but instead presence of adequate factors might permit the environment or particular experiences to mold subsequent illness vulnerability or resilience. Depending on the interactions between gene polymorphisms and the presence of early adverse experiences, subsequent exposure to stressful events or inflammatory immune challenges (e.g., chronic inflammatory diseases, post-stroke inflammation) would lead to sensitization of processes that elicit distinctive variations of brain monoamines, glutamate, growth factors, and/or pro-inflammatory cytokines and influence how they interact in promoting specific depressive phenotypes/subtypes.