title: Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients.
abstract: Traditional schizophrenia pharmacotherapy remains a subjective trial and error process involving administration, titration and switching of drugs multiple times until an adequate response is achieved. Despite this time-consuming and costly process, not all patients show an adequate response to treatment. As a consequence, relapse is a common occurrence and early intervention is hampered. Here, we have attempted to identify candidate blood biomarkers associated with drug response in 121 initially antipsychotic-free recent-onset schizophrenia patients treated with widely-used antipsychotics, namely olanzapine (n=40), quetiapine (n=23), risperidone (n=30) and a mixture of these drugs (n=28). Patients were recruited and investigated as two separate cohorts to allow biomarker validation. Data analysis showed the most significant relationship between pre-treatment levels of heart-type fatty acid binding protein (H-FABP) and response to olanzapine (p=0.008, F=8.6, β=70.4 in the discovery cohort and p=0.003, F=15.2, β=24.4 in the validation cohort, adjusted for relevant confounding variables). In a functional follow-up analysis of this finding, we tested an independent cohort of 10 patients treated with olanzapine and found that baseline levels of plasma H-FABP and expression of the binding partner for H-FABP, fatty acid translocase (CD36), on monocytes predicted the reduction of psychotic symptoms (p=0.040, F=6.0, β=116.3 and p=0.012, F=11.9, β=-0.0054, respectively). We also identified a set of serum molecules changed after treatment with antipsychotic medication, in particular olanzapine. These molecules are predominantly involved in cellular development and metabolism. Taken together, our findings suggest an association between biomarkers involved in fatty acid metabolism and response to olanzapine, while other proteins may serve as surrogate markers associated with drug efficacy and side effects.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: jt455@cam.ac.uk.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tomasik
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Electronic address: emanuel.schwarz@zi-mannheim.de.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Schwarz
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Electronic address: sl588@cam.ac.uk.
authors.forename: Santiago G
authors.initials: SG
authors.lastname: Lago
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany. Electronic address: Matthias.Rothermundt@evkln.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany; Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. Electronic address: markus.leweke@zi-mannheim.de.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.affiliation: Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands; Department "Nieuwe Kennis", Delta Centre for Mental Health Care, Rotterdam, The Netherlands. Electronic address: Nico.van.Beveren@deltapsy.nl.
authors.forename: Nico J M
authors.initials: NJM
authors.lastname: van Beveren
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Electronic address: paulcguest@yahoo.com.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Electronic address: hr288@cam.ac.uk.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.affiliation: Department of Psychiatry, University of Magdeburg, Magdeburg, Germany. Electronic address: steiner.johann@web.de.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: sb209@cam.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D018955:CD36 Antigens / Q000097:blood*; D015331:Cohort Studies; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D000069348:Quetiapine Fumarate / Q000627:therapeutic use; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018955:CD36 Antigens; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D001569:Benzodiazepines; D016753:Interleukin-10; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine
keywords: Biomarker; CD36; FABP3; Olanzapine; Personalised medicine; Schizophrenia