A phase-specific neuroimmune model of clinical depression

Immune dysfunction and pro-inflammatory states in particular have been implicated in the aetiology and pathogenesis of depression. Whilst the onset of an episode and certain symptoms of depression appear well explained by this inflammatory model, the underpinnings of the episodic and progressive nature, as well as relapse and remission status in depression require attention. In this review it is suggested that additional immune factors beyond pro- and anti-inflammatory cytokines may effectively contribute to the understanding of the neurobiology of clinical depression. Considering neurobiological effects of immunomodulatory factors such as T cells, macrophages, microglia and astrocytes relevant to depression, we suggest a neuroimmune model of depression underpinned by dynamic immunomodulatory processes. This perspective paper then outlines a neuroimmune model of clinical phases of depression in an attempt to more adequately explain depression-like behaviours in pre-clinical models and the dynamic nature of depression in clinical populations. Finally, the implications for immunomodulatory treatments of depression are considered.