Modern psychiatry

FROM GENES TO THERAPIES

Hundreds of millions of people around the world are affected by mental disorders. These conditions have been poorly understood for centuries; however, modern psychiatry is now starting to explore the genetic, cellular and neural-
network perturbations that underpin mental illness, with the aim of identifying biological indicators — or biomarkers — that can be used for diagnosis, prognosis and therapeutic intervention.

PROGRESS IN GENETICS

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Fig. 1 | Genome-wide association studies (GWAS).  Scientists compare DNA from thousands of patients to DNA from... [more]

Fig. 1 | Genome-wide association studies (GWAS).  Scientists compare DNA from thousands of patients to DNA from thousands of control subjects, looking for differences (‘SNPs’ or single nucleotide polymorphisms) between the two groups. [less]

<b>Fig. 1 | Genome-wide association studies (GWAS).</b>  Scientists compare DNA from thousands of patients to DNA from thousands of control subjects, looking for differences (‘SNPs’ or single nucleotide polymorphisms) between the two groups.

© Pasieka, Science Photo Library

© Pasieka, Science Photo Library

Genetics has been one of the main driving forces in psychiatric research, as it has been clear for decades that there is heritability in many — if not all — psychiatric conditions. Two research strategies dominate the field of psychiatric genetics today. The first involves the genome-wide association study (GWAS), in which researchers scan and compare entire genomes of people with and without a particular disorder (Fig. 1); this approach has pointed to many common gene candidates with small but significant influences on disorders such as schizophrenia¹. The second involves a search for rare genetic variants that have a strong association with a condition; in autism research, such studies have pinpointed genes that affect how neurons connect to one another².

Genetic strategies come with some caveats. For instance, they are of limited use in conditions, such as mood and anxiety disorders, that have large environmental influences. Furthermore, the identification of genetic variants is often merely a starting point, and genetic data must be complemented by analyses of epigenetic effects, gene-expression profiles, the proteome, metabolic profiles, and neuroendocrinology and imaging data, to yield definitive insights.

Consequently, the fields of transcriptomics, proteomics, metabolomics and functional imaging are developing rapidly. Despite the limitations, genetic studies have revealed important information on putative disease genes and, in some cases, have led to the development of important animal models of psychiatric diseases^3,4.