Toward a Future Psychiatry

Learning Objectives

1. Learn the major role of genetics in psychiatric brain science;
2. Gain awareness of the definition and importance of objective biomarkers for treatment development; and
3. Become informed about current theories of schizophrenia growing out of genetics and neurobiology.

Literature References

1. Hyman, S. E. (2010). The diagnosis of mental disorders: the problem of reification. Annu Rev Clin Psychol 6,155-79. doi: 10.1146/annurev.clinpsy.3.022806.091532.

2. Hyman SE. (2012): Revolution stalled. Sci Transl Med. 4(155):155cm11. doi: 10.1126/scitranslmed.3003142.

3. Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. (2016). Schizophrenia risk from complex variation of complement component 4. Nature. 530:177-83.

4. Singh T, Poterba T, Curtis D, Akil H, et al, (2022). Rare coding variants in ten genes confer substantial risk for schizophrenia, Nature 604: 509-516

5. Trubetskoy V, Pardiñas AF, Qi T, et al. (2022). Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604: 502–508

Abstract

Looking to the future psychiatry faces significant challenges but also has exciting opportunities. The prevalence of mental illness is increasing worldwide without a commensurate increase in resources or in the number of professionals to treat it. Too many of our patients have poor outcomes including homelessness, incarceration, and reduced lifespan. While enlightened policy reforms would help, history teaches us to temper expectations for significant reforms even while advocating energetically. I believe that to significantly improve outcomes we need better diagnostics and treatments. Fortunately, the relevant science has reached an inflection point opening the way. It has long been known that psychiatric disorders are highly genetically influenced, signifying that molecular clues to pathogenesis are contained within our genomes. We gained the ability to access this information with the technologies and computational tools developed with the Human Genome Project. As a result, the last decade has seen psychiatric genetics yield important insights. Using schizophrenia as an illustration I will show how information from genetics has been being integrated with studies of gene expression from postmortem brains, with studies of neurons and glia made from induced pluripotent stem cells
reprogrammed from patient and control blood samples, and from studies of human disease genes engineered into animal genomes. We have reached a point that supports systematic programs aimed at discovering biomarkers and molecular targets for new therapeutics. While success is by no means guaranteed, psychiatry research has entered a time of great promise.