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Over 50 million people worldwide have epilepsy. In nearly 30% of these cases, epilepsy remains unsatisfactorily controlled despite the availability of over 20 antiepileptic drugs. Moreover, no treatments exist to prevent the development of epilepsy in those at risk, despite an increasing understanding of the underlying molecular and cellular pathways. One of the major factors that have impeded rapid progress in these areas is the complex and multifactorial nature of epilepsy, and its heterogeneity. Therefore, the vision of developing targeted treatments for epilepsy relies upon the development of biomarkers that allow individually tailored treatment. Biomarkers for epilepsy typically fall into two broad categories: diagnostic biomarkers, which provide information on the clinical status of, and potentially the sensitivity to, specific treatments, and prognostic biomarkers, which allow prediction of future clinical features, such as the speed of progression, severity of epilepsy, development of comorbidities, or prediction of remission or cure. Prognostic biomarkers are of particular importance because they could be used to identify which patients will develop epilepsy and which might benefit from preventive treatments. Biomarker research faces several challenges; however, biomarkers could substantially improve the management of people with epilepsy and could lead to prevention in the right person at the right time, rather than just symptomatic treatment.

BackgroundThere have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.AimsTo test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).MethodThe 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project.ResultsThe 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome.ConclusionsThe effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5' end of the serotonin transporter gene.