Blood-based Biomarkers for Personalised Medicine Applications in Schizophrenia

The studies presented here were carried out at: Bloed gebaseerde biomarkers voor personalised medicine applicaties in schizofrenie Thesis to obtain the degree of Doctor from the Erasmus University Rotterdam by command of the Rector Magnificus INTRODUCTION Parts of the present chapter were published in: " Blood test for schizophrenia ". " Proteomic profiling in schizophrenia: enabling stratification for more effective treatment ". " Applications of blood-based protein biomarker strategies in the study of psychiatric disorders ". chizophrenia is a mental disorder characterised by occurrence of positive and negative symptoms. Positive symptoms include delusions, hallucinations, disorganised speech and behaviour, and negative symptoms comprise reduced emotions, thinking processes and speech (1). Until recently, schizophrenia diagnosis was mostly based on the revised Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (1) and classified schizophrenia into 5 subtypes: paranoid, disorganised, catatonic, undifferentiated and residual. Another diagnostic handbook used in psychiatry, the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10), also identifies several subtypes of schizophrenia (2). However, these classifications have given rise to criticism. In light of recent research, classification based on symptoms and not on underlying physiological processes is perceived as obsolete (3). DSM-5, published in May 2013, introduced the first substantial changes in schizophrenia diagnosis for 30 years and replaced the subtypes of schizophrenia with disease dimensions, originating from a combination of symptom domains (4). Similar to the Positive and Negative Syndrome Scale (PANSS) (5), this reflects better the complexity of schizophrenia and opens novel avenues for research. However, the DSM-5 schizophrenia diagnosis is still based on symptoms, which is not necessarily associated with aetiology. Significant efforts have been made to find biological signals associated with the disease and its symptoms. The results suggest that schizophrenia is a heterogeneous disease of various causes (genetic, environmental) and different physiological manifestations (altered metabolism, hormonal regulation, immune status). However, these investigations are at an early stage. 1.2. BIOMARKER DISCOVERY IN SCHIZOPHRENIA Biomarkers (or biological markers) are defined as " a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention " (6). According to the Food and Drug Administration (FDA), biomarker research will be one of the main factors driving psychiatric drug development in the next 50 years (7). Biomarker S Introduction 5 1 applications in clinical studies include differential diagnosis, prognosis, prediction of drug response and …