Neonatal levels of acute phase proteins and later risk of non-affective psychosis

Abstract

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log2-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85–0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78–0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32–0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.

Hospital Admission With Infection During Childhood and Risk for Psychotic Illness--A Population-based Cohort Study

“…7 Moreover, we recently reported lower levels of several acute phase proteins, involved in the innate, first-line defense against microbes, in neonatal blood from individuals diagnosed with nonaffective psychosis compared with matched control subjects. 25 Taken together with an increasing literature consistently reporting genetic risk for psychiatric disorders in the MHC regions, 2 these findings suggest that individuals who will later develop nonaffective psychosis might exhibit subtle immune deficiencies that render them more susceptible or vulnerable to early-life infections. The key question is obviously if some of these infections are Hospital admission with all diagnoses except a diagnosis of infection or a psychiatric diagnosis.…”

Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study

“…Evidence for an association with CRP remained after excluding participants who developed schizophrenia within a year of CRP measurement. Despite a large number of cross-sectional studies dating back to the 1990s (Ganguli et al, 1994, Maes et al, 1994) as well as meta-analyses (Miller et al, 2011, Miller et al, 2013, Potvin et al, 2008, Upthegrove et al, 2014) reporting increased CRP and inflammatory cytokines in acutely unwell patients with schizophrenia, longitudinal studies are scarce (Gardner et al, 2013, Khandaker et al, 2014a, Wium-Andersen et al, 2014). Results from the current study reporting a longitudinal association indicate a potentially important role of inflammation in the pathogenesis of schizophrenia, although the findings, based on a limited number of cases, need to be interpreted with caution and require replication in other samples.…”

Expression and regulation of human endogenous retrovirus W elements

“…As for MS, the causes of the low‐grade, inflammatory processes in schizophrenia are not known. A recent study from our laboratory indicates that patients with schizophrenia are born with lower levels of several markers of inflammation as compared to control subjects suggesting that the low‐grade inflammation observed in adult patients is acquired postnatally .…”