Neuroimmune biomarkers in mental illness

Exploration of neuroimmune mechanisms is vital to the understanding of the pathogenesis and pathophysiology of mental disorders. Inflammatory and immune mechanisms are increasingly understood to underpin a number of neuropsychiatric disorders, with an ever-expanding evidence base drawn from basic science to large-scale epidemiological data. Unravelling of these mechanisms should lead to biomarker discovery and potential new avenues for therapeutics that modulate immunological mechanisms. Identification of neuroimmune biomarkers is vital to improving diagnosis, stratification and treatment of mental disorders. There is an urgent clinical need for new therapeutic approaches with poor treatment response and treatment resistance a major problem for many psychiatric disorders including depression and schizophrenia. Neurodegenerative psychiatric disorders such as Alzheimer's also have clear neuroimmune underpinnings and manifest an urgent clinical need for improvements in diagnosis and research towards transformative disease-modifying treatments. This chapter provides some background on the role of the neuroimmune system in mental illness, exploring the role for biomarkers, in addition to reviewing the current state of knowledge in this exciting field. We also reflect on the inherent challenges and methodological pitfalls faced by research in this field, including the complexity of conceptualising multidimensional mental disorders and the dynamic shifting sands of the immune system

Modulation of microglial pro-inflammatory and neurotoxic activity for the treatment of Parkinson’s disease

Parkinson’s disease (PD) is a debilitating movement disorder resulting from a progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. Molecular cloning studies have identified nearly a dozen genes or loci that are associated with small clusters of mostly early onset and genetic forms of PD. The etiology of the vast majority of PD cases remains unknown, and the precise molecular and biochemical processes governing the selective and progressive degeneration of the nigrostriatal dopaminergic pathway are poorly understood. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Studies of postmortem PD brains and various cellular and animal models of PD in the last 2 decades strongly suggest that the generation of proinflammatory and neurotoxic factors by the resident brain immune cells, microglia, plays a prominent role in mediating the progressive neurodegenerative process. This review discusses literature supporting the possibility of modulating the activity of microglia as a neuroprotective strategy for the treatment of PD