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Schizophrenia, Inflammation and Accelerated Aging: a Complex Medical Phenotype

Setting Neuropsychiatry In a Wider Medical Context

In novel research by Campeau et al. (2022), the proteomic analysis of 742 proteins from the blood plasma of 54 schizophrenic participants and 51 age-matched healthy volunteers. This investigation resulted in the validation of the previously-contentious link between premature aging and schizophrenia by testing for a wide variation of proteins involved in cognitive decline, aging-related comorbidities, and biomarkers of earlier-than-average mortality. The results from this research demonstrated that age-linked changes in protein abundance occur earlier on in life in people with schizophrenia. This data also helps to explain the heightened incidence rate of age-related disorders and early all-cause death in schizophrenic people too, with protein imbalances associated with both phenomena being present in all schizophrenic age strata over age 20.

This research is the result of years of medical intrigue regarding the biomedical underpinnings of schizophrenia. The comorbidities and earlier death associated with schizophrenia were focal points of research for many years, but only now have valid explanations been posed to answer the question of the presence of such phenomena. The explanation for the greater incidence rate of early death in schizophrenia was described in this study as the increased volume of certain proteins. Specifically, these included biomarkers of heart disease (Cystatin-3, Vitronectin), blood clotting abnormalities (Fibrinogen-B) and an inflammatory marker (L-Plastin). These proteins were tested for due to their inclusion in a dataset of protein biomarkers of early all-cause mortality in healthy and mentally-ill people published by Ho et al. (2018) for the Journal of the American Heart Association. 

Furthermore, a protein linked to degenerative cognitive deficit with age, Cystatin C, was present in increased volume in schizophrenic participants both under and over the age of 40. This explains why antipsychotics have limited effectiveness in reducing the cognitive effects of schizophrenia. 

In this study, schizophrenics under 40 had similar plasma protein content as the healthy over-60 strata set, including both biomarkers of cognitive decline, age-related diseases 

and death. Schizophrenics under-40 showed the same likelihood for incidence of the latter phenomena compared to the healthy over-60 set. These results could demonstrate the necessity for use of medications often used to treat age-related cognitive decline and mortality-linked protein abundances to treat schizophrenia. 

One of these options include polyethylene glycol-Cp40, a C3 inhibitor used to treat nocturnal haemoglobinuria, which could be used to ameliorate the risk of developing age-related comorbidities in schizophrenic patients. This treatment may be effective in the reduction of C3 activation, which would reduce the opsonisation (tagging of detected foreign products in blood). When overexpressed, C3 can cause the opsonisation of healthy blood cells in a process called haemolysis, which can catalyse the reduction of blood volume implicated in cardiac events and other comorbidities. However, whether or not this treatment would benefit those with schizophrenia is yet to be proven.

The potential of this research to catalyse new treatment options for schizophrenia cannot be understated. Since the publication of Kilbourne et al. in 2009, the impact of cardiac comorbidities in catalysing early death in schizophrenic patients has been accepted medical dogma. The discovery of exact protein targets to reduce the incidence rate of age-linked conditions and early death in schizophrenia will allow the condition to be treated more holistically, with greater observance to the fact that schizophrenia is not only a psychiatric illness, but also a neurocognitive disorder with affiliated comorbidities that have to be prevented adequately.

By Aimee Wilson

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