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Inflammation In Neurological & Psychiatric Diseases

Key Messages

This review article examined findings on the relationship of inflammation with neurological and psychiatric disorders.
Several lines of evidence supported the role of inflammation in the pathophysiology of depression and schizophrenia, including altered levels of proinflammatory cytokines and inflammatory biomarkers in individuals with these conditions. The authors proposed that peripheral immune mediators infiltrating the central nervous system (CNS) may elicit the behavioral symptoms of depression through their adverse effects on relevant neurotransmitter systems and hypothalamic−pituitary−adrenal (HPA) axis balance.

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Background

The following is a summary of Khansari PS, Sperlagh B. Inflammation in neurological and psychiatric diseases. Inflammopharmacol. 2012;20:103–107, which was developed independently of the article authors.

  • Recent evidence has suggested that inflammation may play a key role in the pathology of neurological and psychiatric diseases.

Purpose & Methodology

  • This review article examined the role of neuroinflammation in neurological and psychiatric disorders.
  • The authors reviewed preclinical and clinical research relating to the role of inflammation in neurological diseases, depression and schizophrenia.

Results

Neuroinflammation In Neurological Diseases

  • The term neuroinflammation has been used to describe the innate immune response of the CNS produced by microglia and astrocytes, but more recently there has been evidence to support the idea that infiltration of peripheral inflammatory cells may also contribute to inflammatory-induced CNS pathology, and that injury to the blood−brain barrier and increased vascular permeability are important factors.
  • Microglia, the resident macrophages within the CNS, and astrocytes—which regulate extracellular levels of ions, glucose, and neurotransmitters and contribute to the structure and function of the blood−brain barrier—are pivotal in neuroinflammation.
    • Triggered by infection, inflammation, or neuronal injury, microglia and astrocyte activation results in a range of inflammatory responses and is thought to be prominent in various neurological conditions (Figure 1). Further, in response to ischemic insult, dysregulation of extracellular glutamate concentrations ultimately results in excitotoxicity (Figure 1).
Figure 1. The Role Of Microglia & Astrocytes In Neuroinflammation

Role Of Inflammation In Depression

  • Current evidence has found that depression may arise from alterations in interconnected neuronal networks that are themselves influenced by external pathways, such as the immune system, that convey the effects of environmental factors, in particular stress, to the brain (Table 1).
Table 1. Evidence Supporting The Role Of Inflammation In Depression
Elevated levels of pro-inflammatory cytokines and inflammatory markers are observed in otherwise healthy individuals with depression.
Depression is a common adverse effect of immune therapy. Conversely, immunosuppressant drugs are associated with mood changes.
“Sickness behavior”, the symptoms of which mimic depression, may occur in response to infection and can be evoked by administration of bacterial endotoxin and proinflammatory cytokines.
Anti-inflammatory drugs have shown some efficacy as add-on therapy in the treatment of depression, though results are inconsistent across clinical trials.
  • The authors outlined three pathways by which an altered inflammatory status could lead to the behavioral symptoms of depression:
    • Peripheral immune cells and cytokines crossing into the CNS through a leaky blood−brain barrier may have a deleterious effect on the monoaminergic, glutamatergic and gamma-aminobutyric acid (GABA)ergic neurotransmission systems.
    • Peripheral immune cells may also activate the HPA axis in a positive feedback loop, thereby contributing to HPA axis overdrive and glucocorticoid resistance in depression.
    • Alterations in levels of brain-derived neurotrophic factor in the hippocampus and subsequent changes in adult neurogenesis may also be involved in mood-related changes.

Role Of Inflammation In Schizophrenia

  • The authors outlined the following lines of evidence linking inflammation and schizophrenia:
    • Maternal infection during the second trimester of pregnancy and infection in early childhood are risk factors for the later development of schizophrenia and autism.
    • Some neuropathological studies have reported the presence of mild, chronic inflammation in the brains of patients with schizophrenia.
    • Alterations in serum levels of inflammatory and immune biomarkers in patients with schizophrenia are suggestive of an increased type-2 immune response and decreased type-1 immune response in these patients, though these findings have only been reported in a small number of studies.
    • Selective cyclooxygenase-2 inhibitors have shown some utility as adjunctive therapy in the treatment of schizophrenia in some, but not all, clinical trials.

Discussion

  • The authors concluded that inflammatory mechanisms appear to play a role in the pathogenesis of depression and schizophrenia.

Implications

  • The authors commented that further research is needed to better understand the role of cytokines in neuropsychiatric conditions such as depression, and to establish whether they represent a cause, maintaining factor, or consequence of depression.

Disclosures

This summation has been developed independently of the authors. No disclosures were reported in the original article.