Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression.

Current reviews exploring for unique immune-modulatory profiles of antidepressant classes are limited by focusing mainly on cytokine modulation only and neglecting other aspects of the innate and adaptive immune system. These reviews also do not include recent comparative clinical trials, immune-genetic studies and therapeutics with unique neurotransmitter profiles (e. g., agomelatine). This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system. Antidepressants appear, in general, to reduce pro-inflammatory factor levels, particularly C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6. We caution against conclusions as to which antidepressant possesses the greater anti-inflammatory effect, given the methodological heterogeneity among studies and the small number of comparative studies. The effects of antidepressant classes on adaptive immune factors are complex and poorly understood, and few studies have been conducted. Methodological heterogeneity is high among these studies (e. g., length of study, cohort characteristics, dosage used and immune marker analysis). We recommend larger, comparative studies - in clinical and pre-clinical populations.

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.

Exercising the worry away: how inflammation, oxidative and nitrogen stress mediates the beneficial effect of physical activity on anxiety disorder symptoms and behaviours.

Regular physical activity exerts positive effects on anxiety disorder symptoms, although the biological mechanisms underpinning this effect are incompletely understood. Numerous lines of evidence support inflammation and oxidative and nitrogen stress (O&NS) as important in the pathogenesis of mood and anxiety disorders, and physical activity is known to influence these same pathways. This paper reviews the inter-relationships between anxiety disorders, physical activity and inflammation and O&NS, to explore whether modulation of inflammation and O&NS may in part underpin the positive effect of physical activity on anxiety disorders. Numerous studies support the notion that physical activity operates as an anti-inflammatory and anti-O&NS agent which potentially exerts positive effects on neuroplasticity, the expression of neurotrophins and normal neuronal functions. These effects may therefore influence the expression and evolution of anxiety disorders. Further exploration of this area may elicit a deeper understanding of the pathogenesis of anxiety disorders, and inform the development of integrated programmes including PA specifically suited to the treatment and prevention of anxiety disorders and symptoms.