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

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.

Interacting Roles of COMT and GAD1 Genes in Patients with Treatment-Resistant Schizophrenia: a Genetic Association Study of Schizophrenia Patients and Healthy Controls

“…Regarding COMT gene, several studies have suggested that this gene could be related to treatmentrefractoriness or responsiveness to medications, and most of those studies demonstrated that Met-allele carriers could be linked to treatment-refractoriness [Inada et al, 2003;Sagud et al, 2018;Hajj et al, 2019] with the exception of one report [Terzić et al, 2016], which was in line with our present nding. However, some research groups examining COMT and GAD1 suggested that the interacting effects of both genes could not simply explain the synthesis of GABA and the clinical phenotypes in schizophrenia.…”

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders

“…It has also been hypothesized that patients with TR may share genetic underpinnings (Nucifora et al, 2019). This is further supported by findings showing that family members of patients with TR are more likely to have a diagnosis of schizophrenia in comparison with family members of responsive patients with schizophrenia (Hajj et al, 2019;Silverman et al, 1987), indicating a common genetic component (Joober et al, 2005). Taken together, these findings indicate that TR might be at least partly determined by the burden of genetic risk for schizophrenia.…”

Profiles and factors associated with schizophrenia in eastern Ethiopia: A matched case-control study

“…It might also be due to shared risk of genetic markers, environmental exposures or a combination of these factors with family history of mental illness ( 32 ). Previous studies have also shown that family history of mental illness have biological/hereditary effects and that other psychiatric problems in the family could indicate similar etiological factors in the development of the problems ( 33 , 34 ).…”