Is inflammation the key factor in psychosis? AJP: Ahead of print: Oct, 2015.

20.10.2015

Patho etiology of schizophrenia is not understood to any sufficient degree. Neuro inflammation is one of the  theories that is gaining momentum. Role of microglia in schizophrenia is supported by some evidence. Direct and indirect evidence for microglial activation ( PET studies, postmortem studies) is gradually emerging.

van Berckel BN et al in 2008 reported the first PET study showing elevated microglial activity in psychosis.Studies so far were done on patients who already have the disorder. What about those at higher risk for psychosis? We already know that , more than one third of individuals in high risk category would develop psychosis in near future.

Would inflammation be more marked  in ultra high risk for psychosis  individuals as compared to control? Peter S. Bloomfield ( imperial college, London) and team of researchers  addressed this key question.

56 individuals ( from London) participated in this study. 14 met criteria for ultra high risk. 14 age matched control individuals and 14 patients with schizophrenia were also studied. Ultra-high-risk individuals were assessed with the Comprehensive Assessment of the At-Risk Mental States. All participants underwent Brain MRI and PECT imaging.

Results

Distribution volume ratios  of the ligand (= elevated microglial activity) was significantly high  ultra-high-risk individuals when compared with matched comparison subject. This was seen in total gray matter and frontal lobe and temporal lobe gray matter. More symptom score ( in ultra high risk group) meant that they have more microglial activation in grey matter (total). The effect observed is large ( Cohen’s d > 1.2). Microglial activity did not correlate with depressive symptoms , suggesting that it is specific to psychosis. Ultra high risk individuals were not on medications and the effect cannot be attributed to previous illness or treatment. The study also show that  microglial activity is elevated in  people with schizophrenia relative to comparison subjects, with a large effect size (Cohen’s d .1.7).

This is the first evidence  of  elevated brain microglial activity in people at ultra high risk of psychosis. It also show that greater microglial activity is associated with greater symptom severity.

Limitations

Relatively small study. It is not known whether such changes persist over time.

Comments

There has been interest in anti-inflammatory agents as beneficial agents in psychotic disorders. The question here is: Would control of inflammatory activity in high risk stage prevent the onset of psychosis? It would also be interesting to see whether general anti inflammatory drugs or  target specific agents are required to test this hypothesis.

Summary of the article 

Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [11C]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. 2015 Oct 16:appiajp201514101358. [Epub ahead of print]

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