Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients
Leweke, F Markus
van, Beveren Nico JM
Guest, Paul C
Brain, Behavior, and Immunity
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Tomasik, J., Schwarz, E., Lago, S., Rothermundt, M., Leweke, F. M., van, B. N. J., Guest, P. C., et al. (2015). Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. Brain, Behavior, and Immunity, 52 178-186. https://doi.org/10.1016/j.bbi.2015.10.019
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.
Schizophrenia, Olanzapine, Biomarker, Personalised medicine, FABP3, CD36
This work was supported by the Stanley Medical Research Institute (SMRI); the European Union FP7 SchizDX research programme (grant reference 223427); the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (nr. 286334, PSYCH-AID project); by the Virgo consortium, funded by the Dutch Government (project number FES0908); by the Netherlands Genomics Initiative (project number 050-060-452); by the Dutch Fund for Economic Structure Reinforcement, the NeuroBasic PharmaPhenomics project (no. 0908) and by the Engineering and Physical Sciences Research Council UK (EPSRC CASE studentship and Impact Acceleration Award).
External DOI: https://doi.org/10.1016/j.bbi.2015.10.019
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252856
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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