Unmet needs in precision psychiatry

A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response. The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposure. We also alert to errors in the original data that had been carried over. Specifically, primers meant to amplify the HTR1A gene aligned to the BDNF gene sequence. Alleles had been confounded owing to DNA strand ambiguities and demographic information proved inaccurate. In the light of these findings, adherence to PRISMA guidelines and use of the Newcastle-Ottawa Scale did not safeguard against bias. More after action reviews are encouraged to identify factors likely to interfere with estimates of genetic risk in large data sets. These may result from pooling of ethnic groups, the use of binary data or other formats that are not human-readable, the introduction of surrogate identifiers and a failure to reverse-engineer previously published experimental protocols. Unless the above challenges are met, sequence variants are unlikely to inform personalized medicine strategies in psychiatry.