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Inflammation and the brain, in the context of mental health and illness

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Mental, neurological and substance use disorders account for a significant proportion of the global burden of disease, surpassing that of cardiovascular disease and cancer. However, despite major research funding over the past 20 year our understanding of the etio-pathophysiology of many of these complex ...

Mental, neurological and substance use disorders account for a significant proportion of the global burden of disease, surpassing that of cardiovascular disease and cancer. However, despite major research funding over the past 20 year our understanding of the etio-pathophysiology of many of these complex disorders remains incomplete.

Far from being an immune privileged organ, it is now recognized that inflammatory and immune processes play a key role in the normal brain development and functioning of the central nervous system. In keeping with these findings, the past two decades have witnessed a burgeoning area of pre-clinical and clinical research linking inflammatory/immune processes to the brain in both health and disease. Microglial cells have been shown to play an active role in neurogenesis, synaptic plasticity, neuronal surveillance and synaptic stripping in the healthy brain. Inflammatory/immune mediators are now thought to contribute to the pathogenesis of psychiatric disorders, thus providing an opportunity to explore novel diagnostic and therapeutic target, at least in a ‘cohort’ of vulnerable individuals. For example, opioids are now known to bind to toll like receptor (TLR4) along with the classic opioid receptors, thus affecting the mesolimbic dopamine system, possibly explaining altered opioid reward behaviors. Inflammatory/immune markers may therefore be potential biomarkers, aiding diagnosis and predicting prognosis. This we also think will lead to tailored targeted treatments, thereby allowing stratification of what remain a group of heterogeneous disorders. Future work will focus on cementing the precise role of inflammation in psychiatric disorders through sophisticated animal models and clinical neuroscience.

While the above mentioned findings have demonstrated potential pathways through which inflammation may contribute to the normal brain function and pathology, another question is what makes people prone to develop high levels of inflammation. Observational studies have shown that people with psychiatric disorders are at increased risk of developing cardiometabolic illnesses, where inflammation is believed to play a pathogenic role. Curiously, the converse is also true, individuals with a primary inflammatory illness – both “high grade”, like inflammatory arthritides and “low grade” inflammation like cancer, or coronary artery disease - are at greater risk of developing a psychiatric disorder. While these have traditionally been attributed to poor health choices and health (physical and psychiatric) care utilization, recent research suggests that such simplistic modelling of psychiatric and physical health co-morbidities may not be useful and may indeed be misleading. This has led a call to examine the role of immune/inflammatory and cardiometabolic risk factors as common endophenotypes of both physical and psychiatric illnesses. In other words, there may be common genetic and environmental factors that may contribute to chronic cardiometabolic illnesses like obesity and psychiatric illnesses like major depression.

We propose to welcome a series of articles relevant to this rapidly developing field in psychiatry. We are particularly interested in encouraging clinical and pre-clinical studies with novel findings that demonstrate a relationship between inflammatory/immune and cardiometabolic markers and central nervous system structure and functions (using structural, molecular and functional neuroimaging and behavioral/cognitive neuroscience methodology), particularly in the context of psychiatric disorders.


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