Antipsychotics and beta cell toxicity

Schizophrenia affects around one in 100 people in the UK and presents with clinical features that include hallucinations and delusional perceptions. Over the past 30 years, the development of ‘atypical’ antipsychotics has reduced the incidence of extrapyramidal side effects (EPSEs) that were commonly seen with ‘typical’ agents, and has revolutionised the treatment of this condition. Nonetheless, despite treatment, patients with schizophrenia have a 10- to 20-year lower life expectancy compared to the general population.

Recent evidence suggests that this increased mortality may be due to the development of Metabolic Syndrome (MeS, poor glucose tolerance, dyslipidaemia, central obesity, hypertension). The cause of MeS is not clear, but may be related to the use of antipsychotics. Indeed, atypical agents such as olanzapine are known to elevate blood glucose and lipid concentrations, and routine monitoring of glucose is recommended during treatment. The mechanism through which olanzapine alters glucose homeostasis is not currently known – understanding how this drug produces these effects could inform future strategies to reduce medication-related harm. Scientists from the BSCMO and the Centre for Stress and Age-Related Disease (STRAND) have gathered preliminary data showing that olanzapine is directly toxic to insulin-secreting beta-cells (dysfunctional beta-cells can cause MeS). We have also shown that this toxicity may be initiated through activation of the mammalian target of rapamycin signalling pathway. We have recently secured University of Brighton funding for a studentship, which will commence in October 2016, to develop this project further.

Data suggested that a commonly prescribed atypical antipsychotic – olanzapine – may cause beta cell toxicity through effects on the mammalian Target of Rapamycin signalling pathway. By understanding the mechanism through which these agents induce MeS, we can then begin to explore methods to reduce toxicity. This work is prime example of a clinical problem, that affects a large proportion of the population, being solved using the scientific and technical expertise of academics at the University of Brighton.