Neuroimmune Biomarkers in Mental Illness

Abstract

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.

Is Molecular Inflammatory Profiling a Useful Tool for Personalized Brain Stimulation in Psychiatric Disorders?

“…In view of the low level of evidence, experimental, and in particular clinical exploration of mechanisms of neuroimmune communication in subjects treated with brain stimulation is highly recommended to close gaps between neuroscience and clinical practice. In contrast to other approaches, peripheral biofluids (saliva, serum) are easily accessible and suitable for wide-spread application and data acquisition in future clinical trials (3).…”

“…For one, the dynamic and heterogeneous (interindividual and intraindividual variability) nature of psychiatric illness per se represents a considerable confounder for diagnosis, patient selection, and treatment response in a currently undefined frame (2,3). Secondly, as suggested by panel recommendations and expert opinions, several randomized-controlled, comparative studies have been conceptualized to analyze different interventions and ensure rigorous assessment of standardized stimulation parameters (i.e., dose-response relationship) (3).…”

“…For one, the dynamic and heterogeneous (interindividual and intraindividual variability) nature of psychiatric illness per se represents a considerable confounder for diagnosis, patient selection, and treatment response in a currently undefined frame (2,3). Secondly, as suggested by panel recommendations and expert opinions, several randomized-controlled, comparative studies have been conceptualized to analyze different interventions and ensure rigorous assessment of standardized stimulation parameters (i.e., dose-response relationship) (3). In view of the rapid technical progression and availability of the applied noninvasive and invasive brain stimulation technologies, such systematically-driven data acquisition of stimulation parameters (target, frequency, intensity, duration) will help establish reliable dose-response relationships relevant for distinct psychiatric disease subtypes (biotyping), identified through imaging, electrophysiology, psychosocial characteristics, advanced statistical models, and (epi-) genetics (2)(3)(4)(5).…”

<p>Weighted Gene Coexpression Network Analysis Identifies Specific Modules and Hub Genes Related to Major Depression</p>

“…5 To date, the microarray technique has increasingly been used for life science research purposes, and bioinformatic data-mining of the gene has widely been used for differential expression analysis to identify novel diagnostic and therapeutic biomarkers of diseases. 6,7 Extensive research efforts investigating depression have been performed in past decades, and potential new therapeutic targets are being identified, including oxidative stress, immune system effects 8 and neuroinflammation 9 in the central nervous system (CNS), through cytokines, which regulate brain activities and emotions. In particular, a recognition that immune system actions profoundly impact mood regulation 10 has been particularly well established for inflammatory signals from the innate immune system linked to depression in human and rodent studies.…”

Anti-Inflamatory Activity of Neolignan Compound Isolated from the Roots of Saururus chinensis

“…Inflammation is a biological response that protects the body against harmful stimuli. Inflammatory abnormalities underlie a number of diseases including atherosclerosis [ 1 ], mental illness [ 2 , 3 ], sarcopenia [ 4 ], and obesity [ 5 ]. For over a decade, nonsteroidal anti-inflammatory drugs (NSAIDs) have been commonly used to alleviate inflammatory abnormalities.…”