Clinical and Genetic Factors Associated with Resistance to Treatment in Patients with Schizophrenia: A Case-Control Study.

Aline Hajj,Jocelyne Azar,Saria Sahyoun,Chadia Haddad,Sahar Obeid,Lydia Rabbaa Khabbaz,Souheil Hallit

doi:10.3390/ijms20194753

Abstract

Objectives: To assess clinical and genetic factors affecting response to treatment in a sample of patients with schizophrenia (treatment-resistant patients versus treatment responders). We also aimed at examining if these factors are different when we consider two different resistance classifications (the positive and negative syndrome scale, PANSS and the brief psychiatric rating scale, BPRS). Material and Methods: A case-control study included treatment-resistant patients and good responders. Patients were stratified in two groups based on the established criteria for treatment-resistant schizophrenia using BPRS and PANSS. The study was approved by the ethical committees (references: CEHDF1017; HPC-017-2017) and all patients/legal representatives gave their written consent. Clinical factors were assessed. DNA was obtained using a buccal swab and genotyping for OPRM1, COMT, DRD2 et MTHFR genes using the Lightcycler® (Roche). Results: Some discrepancies between the BPRS and PANSS definitions were noted in our study when assessing the patients’ psychopathological symptoms and response to treatment. The multivariable analysis, taking the presence versus absence of treatment resistance as the dependent variable, showed that that family history of schizophrenia, university studies, time since the beginning of treatment and chlorpromazine equivalent dose as well as the COMT gene are associated with resistance to treatment. In addition, a gender-related difference was noted for COMT SNP; men with at least one Met allele were more prone to be resistant to treatment than Val/Val patients. Conclusion: Uncovering the clinical and genetic factors associated with resistance to treatment could help us better treat our schizophrenic patients in a concept of personalized medicine.

Highlights

Schizophrenia (SCZ) is a severe neurodevelopmental disorder affecting 1% of the general population worldwide [1]
We aimed to examine if these factors are different when we consider two different resistance classifications (PANSS and brief psychiatric rating scale (BPRS))
When selecting males alone, the results showed that the COMT VM and MM genotypes were associated with resistance to treatment

Summary

Introduction

Schizophrenia (SCZ) is a severe neurodevelopmental disorder affecting 1% of the general population worldwide [1]. A variety of representative scales, such as the positive and negative syndrome scale (PANSS), the brief psychiatric rating scale (BPRS), the scale for the assessment of negative symptoms (SANS) and the clinical global impression (CGI) clinical impression, were designed primarily to measure symptoms [1,2]. Using these different scales, studies have shown that treatment-resistant patients develop persistent positive psychotic symptoms, more pronounced negative symptoms and more severe cognitive impairment compared to treatment-responsive patients. Clinical and social factors include the age of onset of the disease, the duration of illness, the severity of the psychotic symptoms, the compliance to the pharmacological treatment and to non-pharmacological interventions [4,10,11,12]

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