Patho-etiology of psychosis is not well understood. Neuro inflammation is one possibility. Studies have suggested that microglia, the immune cells of the CNS, are involved. Pro inflammatory cytokines ( peripheral markers) are elevated in psychosis. Grey matter volume reductions are seen parallel to such elevations.These changes are seen in both schizophrenia and in ultra high risk groups.
Can we measure the microglial activity in the brain ? PET imaging using radioligands specific for a protein (18kD translocator-protein (TSPO)) which is expressed on microglia is one possibility. This method of enquiry has shown increased microglial activity in individuals with schizophrenia. Severe symptoms of schizophrenia is often proceeded by a prodromal phase of attenuated symptoms. One third of individuals who meet high risk criteria develop psychosis within 2 yr follow up period. Would Ultra High Risk individuals also show elevated microglial activity ?
Peter Bloomfield and team from Imperial College London studied this in 58 subjects. This included 14 ultrahigh risk patients & 14 controls, 14 schizophrenia patients & their 14 controls.Ultra-high-risk individuals were assessed with the Comprehensive Assessment of the At-Risk Mental States. All subjects underwent MRI and PET study.
There were no demographic differences between different groups. The binding ratio of the ligand [11C]PBR2 was elevated in Ultra high risk group and schizophrenia group.The elevation in ultra high risk group was specific to the subclinical psychotic symptoms. These high risk individuals were not on any medications and were new to services, we could assume that the observed changes are not due to medications or previous illness. During the study, one participant developed psychosis and this patient had the highest binding of ligand.
This study show that elevated microglial activity predates diagnosable , frank psychosis.
Limitations: Researchers used a relative quantification method ( ie binding expressed as ratio of binding in cortical grey matter to whole brain) and it is not clear whether high binding ratio is due to higher TSPO expression in cortical grey matter or lower expression elsewhere. We do not now know the predictive power of such high binding . i.e. does high binding mean more transition to florid psychosis? The association of high bidding ratio with high prodromal symptom severity observed in this study point to the higher chance of tradition with high binding.
It is unclear whether the 18kD translocator-protein (TSPO) activity expressed by microglia is a protective mechanism triggered by disease process or it is a primary neuro inflammatory process linked to risk factors for psychosis and the development of subclinical symptoms.
The observation that anti inflammatory medications may reduce negative symptoms (for example: Minocycline reduce symptoms early in illness) and that some antipsychotics possess some degree of anti-inflammatory activity add to to the idea that neuro inflammatory process is involved in psychosis.
Neuro inflammation is emerging as a consistent finding in psychosis. It needs to be seen how microglial activity changes over the time when individual’s mental state /diagnosis changes.
Summary of the article
Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study. Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, Bloomfield MA, Bonoldi I, Kalk N, Turkheimer F, McGuire P, de Paola V, Howes OD.Am J Psychiatry. 2016 Jan 1;173(1):44-52.