Genome-Wide Association Study of Antidepressant Treatment-Emergent Suicidal Ideation

Emergence of suicidal ideation (TESI) during treatment with antidepressants in major depression led to a black box warning. We performed a genome-wide association study to identify genetic markers, which increase the risk for this serious side effect. TESI was evaluated in depressed in-patients (N = 397) and defined by an emergence of suicidal thoughts during hospitalization without suicidal thoughts at admission using the suicide item (3) of the Hamilton Depression Rating Scale. Genotype distribution of 405.383 single-nucleotide polymorphisms (SNPs) in patients with TESI (N = 32/8.1%) was compared to patients without increase in suicidal ideation (N = 329/82.9%) and to a subgroup never reported suicidal ideation (N = 79/19.9%). Top results were analyzed in an independent sample (N = 501). None variant reached genome-wide significance, the best associated SNP was rs1630535 (p-value = 1.3 x 10(-7)). The top 79 SNPs could be analyzed in an independent sample, and 14 variants showed nominal significant association with the same risk allele in the replication sample. A discriminant analysis classifying patients using these 79 SNPs revealed a 91% probability to classify TESI vs non-TESI cases correctly in the replication sample. Although our data need to be interpreted carefully owing to the small numbers in both cohorts, they suggest that a combination of genetic markers might indeed be used to identify patients at risk for TESI. Neuropsychopharmacology (2012) 37, 797-807; doi: 10.1038/npp.2011.257; published online 26 October 2011