MedicalResearch.com Interview with:
Prof Sabine Bahn MD PhD MRCPsych FRSB
Cambridge Centre for Neuropsychiatric Research
Jakub Tomasik, PhD
Department of Chemical Engineering and Biotechnology
University of Cambridge
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Schizophrenia patients are at increased risk of impaired glucose metabolism, yet the comorbidity between the two conditions cannot be fully explained by known risk factors such as obesity, smoking, stress or antipsychotic medication. Previous family and genome-wide studies have suggested that the co-occurrence between schizophrenia and impaired glucose metabolism might be due to shared genetic factors, as exemplified by increased risk of diabetes in first-degree relatives of schizophrenia patients, but the biological mechanisms underlying this association remain unknown.
We examined the association between insulin resistance, schizophrenia polygenic risk and response to treatment in 58 drug-naive schizophrenia patients and 58 matched healthy individuals while controlling for a range of demographic (age, gender, body mass index), lifestyle (smoking, alcohol and cannabis use) and clinical (psychopathology scores, treatment drug) factors.
We found that insulin resistance, a key feature contributing to the development of type 2 diabetes, significantly correlated with schizophrenia polygenic risk score in patients, with higher genetic risk of schizophrenia associated with increased insulin resistance. Furthermore, we found that patients with higher insulin resistance were more likely to switch medication during the first year of treatment, which implies lower clinical response.
MedicalResearch.com: What should readers take away from your report?
Response: These results suggest that insulin resistance and schizophrenia are genetically linked and that schizophrenia patients presenting with insulin resistance might constitute a distinct patient subgroup. This is consistent with previous findings of altered glucose metabolism in the brain and periphery in subsets of patients with schizophrenia. Because these patients show diminished response to antipsychotic medication, they might require personalized treatment tailored to their endophenotype.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future large-scale pharmacogenomic studies in drug-naive patients with longitudinal clinical follow-up will help to further examine the association between insulin resistance, schizophrenia and antipsychotic treatment response, in addition to determining the effects of other lifestyle factors such as diet and exercise, identifying specific genetic variants underlying shared susceptibility to schizophrenia and insulin resistance, and potentially guiding the development of novel, personalised treatment approaches.
MedicalResearch.com: Is there anything else you would like to add?
Response: We are grateful to the individuals who participated in the study for sample donation, and the technical and clinical support staff at the affiliated institutions for collection of samples, clinical data and technical support.
This work was supported by grants from the Stanley Medical Research Institute.
Tomasik J, Lago SG, Vázquez-Bourgon J, et al. Association of Insulin Resistance With Schizophrenia Polygenic Risk Score and Response to Antipsychotic Treatment. JAMA Psychiatry. Published online April 03, 2019. doi:10.1001/jamapsychiatry.2019.0304
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