Abstract
In the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (corrected P < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrected P-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder.
Highlights
Despite decades of research, the aetiology of schizophrenia is poorly understood
We monitored 77 proteins (147 peptides) in 139 serum samples from Cologne. These samples were randomly assigned to two 96-well plates, the second plate was half filled, and run over one and a half weeks on the mass spectrometry (MS)
We used the coefficient of variation (CV) to quantify the degree of variation in the relative peptide abundances measured in a pooled serum sample
Summary
The aetiology of schizophrenia is poorly understood. Schizophrenia is a severe and disabling psychiatric disorder involving impairments in perception, cognition and motivation that usually become evident in late adolescence or early adulthood.Early diagnosis of schizophrenia is beneficial for patients as shorter periods of untreated psychosis have been linked to better patient outcomes[1]. The aetiology of schizophrenia is poorly understood. Schizophrenia is a severe and disabling psychiatric disorder involving impairments in perception, cognition and motivation that usually become evident in late adolescence or early adulthood. Diagnosis of schizophrenia is beneficial for patients as shorter periods of untreated psychosis have been linked to better patient outcomes[1]. As there are no diagnostic tests for schizophrenia, diagnosis is still based on the evaluation of signs and symptoms in clinical interviews. Misdiagnosis is common[2] as patients are required to acknowledge the occurrence of symptoms of psychosis, such as hallucinations and delusions. Other psychiatric disorders can present with overlapping symptoms
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