Universität zu Köln

Tomasik, Jakub ORCID: 0000-0002-2127-4487, Schwarz, Emanuel, Lago, Santiago G., Rothermundt, Matthias, Leweke, F. Markus ORCID: 0000-0002-8163-195X, van Beveren, Nico J. M., Guest, Paul C., Rahmoune, Hassan, Steiner, Johann ORCID: 0000-0002-2611-2268 and Bahn, Sabine (2016). Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. Brain Behav. Immun., 52. S. 178 - 187. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2139

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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, beta = 70.4 in the discovery cohort and p = 0.003, F = 15.2, beta = 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, beta = 116.3 and p = 0.012, F = 11.9 beta = -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. (C) 2015 The Authors. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tomasik, Jakub UNSPECIFIED orcid.org/0000-0002-2127-4487 UNSPECIFIED Schwarz, Emanuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Lago, Santiago G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothermundt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Leweke, F. Markus UNSPECIFIED orcid.org/0000-0002-8163-195X UNSPECIFIED van Beveren, Nico J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guest, Paul C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahmoune, Hassan UNSPECIFIED UNSPECIFIED UNSPECIFIED Steiner, Johann UNSPECIFIED orcid.org/0000-0002-2611-2268 UNSPECIFIED Bahn, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286132
DOI:	10.1016/j.bbi.2015.10.019
Journal or Publication Title:	Brain Behav. Immun.
Volume:	52
Page Range:	S. 178 - 187
Date:	2016
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2139
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BINDING PROTEIN; DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; ARACHIDONIC-ACID; WEIGHT-GAIN; MATRIX METALLOPROTEINASES; ATYPICAL ANTIPSYCHOTICS; INTERLEUKIN-10 GENE; MULTIPLE ROLES; PLACEBO Multiple languages Immunology; Neurosciences; Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28613