Letter to the Editor

Genetic variation in cytokine genes and risk for transition to psychosis among individuals at ultra-high risk

A personalized medicine approach seems to be particularly applicable to psychiatry. Indeed, considering mental illness as deregulation, unique to each patient, of molecular pathways, governing the development and functioning of the brain, seems to be the most justified way to understand and treat disorders of this medical category. In order to extract correct information about the implicated molecular pathways, data can be drawn from sampling phenotypic and genetic biomarkers and then analyzed by a machine learning algorithm. This review describes current difficulties in the field of personalized psychiatry and gives several examples of possibly actionable biomarkers of psychotic and other psychiatric disorders, including several examples of genetic studies relevant to personalized psychiatry. Most of these biomarkers are not yet ready to be introduced in clinical practice. In a next step, a perspective on the path personalized psychiatry may take in the future is given, paying particular attention to machine learning algorithms that can be used with the goal of handling multidimensional datasets.

We investigated IL1B genetic variation previously associated with risk for transition to psychosis for its association with gene expression in human post-mortem dorsolateral prefrontal cortex (DLPFC) from 74 (37 schizophrenia, 37 control) individuals and brain structure in 92 (44 schizophrenia, 48 control) living individuals. The IL1B A-G-T ‘risk for psychosis transition’ haplotype (rs16944|rs4848306|rs12621220) was associated with upregulation of IL1B mRNA expression in the DLPFC as well as reduced total grey matter and left middle frontal volumes and enlarged left lateral ventricular volume. Our results suggest IL1B genetic variation may confer psychosis risk via elevated mRNA expression and/or brain structure abnormalities.

Upon completion of the Human Genome Project, there was hope that psychiatry management would become more precise, and early identification, diagnosis, and treatment would be assisted by genetic testing. However, 15 years have passed, and genetic testing in psychiatry is not yet mainstream. In this chapter, we provide a concise overview of the current evidence for genetic testing in psychiatry, along with recommendations for future work aimed at strengthening this evidence. Although there are formidable challenges to be addressed before genetic testing is ready for early identification or diagnosis of psychiatric disorders, the evidence base for genetic testing to assist with the optimization of pharmacological treatment is emerging, and has the potential to facilitate implementation into the clinic.