A biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes or pharmacological responses to an intervention,”1 explained Professor A Szulc, Medical University of Warsaw, Poland.
Sterile inflammation of the brain is common and a potential cause of psychiatric disorders
Psychiatric disorders result from a combination of stress, environmental and genetic factors, said Professor Mariusz Ratajczak, Warsaw Medical University, Poland and James Brown Cancer Centre, Louisville, KY.
Inflammation-related abnormalities are common in patients with psychotic disorders, he explained, and these include:
- elevated levels of circulating pro-inflammatory cytokines and chemokines
- increased numbers of circulating monocytes and neutrophils
- enhanced microglial, astrocyte and endothelial cell reactivity to pro-inflammatory signals2
Severe depression is also often comorbid with chronic inflammatory conditions, and patients with pre-existing inflammatory diseases are more susceptible to developing mood disorders than healthy individuals.
These findings indicate a cross-talk between the innate and adaptive immune systems, explained at least partially by co-evolution of the systems, Professor Ratajczak said.2 He suggested that sterile inflammation of the brain due to activation of innate immunity — a common event triggered by physical, chemical or metabolic damage but not microbial infection — is a cause of psychiatric disorders. Complement cascade cleavage products (C3a and C5a) are new markers of sterile inflammation in the brain, he added.
“Sterile inflammation of the brain due to activation of innate immunity — a common event triggered by physical, chemical or metabolic damage but not microbial infection — is a cause of psychiatric disorders” Professor Ratajczak
Professor Ratajczak also highlighted the role of microglia (which account for 10–15% of all cells in the brain) as an extension of cellular immunity in the brain. As key cells in brain maintenance, microglia are extremely sensitive to even small pathological changes.
Other key players in the pathological process include changes in the release of danger-associated molecular pattern molecules (DAMPs) with aberrant ATP-mediated purinergic signalling and activation of the complement and coagulation cascade in the sterile inflammation. In contrast, the inflammation-limiting effects exerted by heme oxygenase-1 (HO-1) have beneficial effects in inflammatory processes.2
The heterogeneity of psychiatric disorders presents many challenges in diagnosis and treatment, but patient stratification is required to enable precision or personalised psychiatry, said Professor Sophia Frangou, Icahn School of Medicine, Mount Sinai, NY.
In an attempt to stratify patients with schizophrenia, Professor Frangou and her team have used a person-based similarity index (PBSI) — an individual person’s brain structural profile that considers all relevant morphometric measures as features of a single vector.3 They have found:
- measures of global structural variability, suggesting that patient heterogeneity lies in cortical regions; and
- measures of regional structural variability, implicating the middle frontal gyrus involved in executive functions and cognitive control, and middle temporal gyrus, involved in language processing and memory.
DSM diagnoses encompass heterogeneous clinical descriptions and cannot yet be guided by biological data, said Professor Jerzy Samochowiec, Pomeranian Medical University, Szczecin, Poland. He described the complex genetics of psychiatric disorders and suggested that any single genetic variant is unlikely to be useful in enabling diagnosis; because it appears that many genes are exerting a small effect on risk.